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['The aim of the present study was to find a possible polymorphism in the promoter region of the osteopontin (OPN) gene, as a potential mutation region, connected with the transcription factor-binding sites or regulatory sequences and to estimate the expression of this gene in ovaries and oviduct of sows.', "Sixty wbp x pbz sows after the first mating were slaughtered and tissues samples of the ovaries and oviduct were taken. Primer pairs for PCR analysis were designed on the basis of swine osteopontin 5' end sequence driven from GenBank. This study's amplified DNA fragment, spanning 274 bp of the promoter region, was chosen because of its contents of tree specific sites: type II collagen silence sequence (CACCTCC) at -682 (from the transcription initiation site), glucocortIcoid response site (TGTCCT) at -658 and CAAT box -592. This DNA fragment was subjected to a MSSCP analysis.", 'A different MSSCP pattern was shown which indicates that mutation is located in this region. The samples of different conformers were sequenced and the A --> G transitions was identified in two positions -617 and -608. Restriction analysis of the DNA was performed, but unfortunately none of the known restriction enzymes recognized the novel SNPs, which is why the specific primer pairs characteristic for nucleotide A or for nucleotide G were chosen. In the second stage of the presented study the total RNA was extracted from the tissues of the ovaries and oviduct and the complementary DNA (cDNA) was synthesized.'] |
["Few studies of gene variants that affect estrogen activity investigate their association with risk for Alzheimer's disease (AD) in women of different ethnicities. We investigated the influence of CYP19 polymorphisms on risk for AD in a multiethnic cohort of women, with individual ethnicity assessed by genetic population ancestry informative markers (AIMs) as well as by self-identified ethnicity.", 'Among 1,686 women participating in the Washington Heights Inwood Columbia Aging Project, association with risk for AD was assessed for 41 single nucleotide polymorphisms (SNPs) on the CYP19 gene using multivariable logistic regression, adjusting for age, presence of an APOE ε4 allele, years of education, and body mass index.', 'Risk for AD was associated with 6 SNPs in women of predominantly Caucasian AIMs-defined ancestry. Of these, 2 were also associated with decreased risk of AD in women of admixed/Hispanic AIMs ancestry. Two separate SNPs were found to be protective in women of predominantly African AIMs-based ancestry.'] |
['Prostaglandin E2 (PGE2) is a major contributor to the production and maintenance of immunosuppression in injured and septic patients. Although the synthesis of PGE2 by various enzymes has been elucidated, the regulatory mechanism of these enzymes is not clear. The purpose of this study was to determine the role of MAPK cascades in COX-2 gene activation by lipopolysaccharide (LPS)-stimulated macrophages (Mphi).', 'RAW 264.7 cells, a mouse Mphi cell line, were exposed to Escherichia coli LPS (10 microg/ml) in the presence of PD98059, a selective inhibitor of MAPKP44/P42, and SB202190, a selective inhibitor of MAPKP38. COX-2 mRNA expression and PGE2 production were measured by Northern Blot assay and ELISA, respectively. Mphi nuclear factor (NF)kappaB and cAMP-response element (CRE) activities were determined by electrophoretic mobility shift assays.', 'LPS stimulation increased Mphi COX-2 mRNA expression and PGE2 production. PD98059 or SB202190 attenuated LPS-induced COX-2 mRNA as well as PGE2 production in a dose-dependent fashion. Inhibition of MAPKP44/P42 or MAPKP38 had no effect on NFkappaB activation but reduced CRE activity induced by LPS stimulation.'] |
['Follicular lymphoma is an indolent lymphoma with a long median overall survival. However, a considerable number of patients die within the first 2 years after the onset of the disease. Because the treatment options vary with respect to antitumor effect and potential toxic adverse effects, the identification of high-risk patients would be helpful in directing therapeutic decisions in individual patients. Several histopathologic biomarkers for risk stratification have been suggested, but most markers have not been validated in patients treated in prospective trials.', 'We report a comprehensive approach to evaluate histopathologic biomarkers, including WHO grade, histology, and proliferation and quantitation of immune bystander cells, in 158 patients with nodal advanced-stage follicular lymphoma treated first line within a randomized trial.', 'Tumor sclerosis was a significant prognostic marker of poor overall survival that was independent of the Follicular Lymphoma International Prognostic Index (FLIPI). WHO grade, proliferation, and total T-cell or macrophage content were not associated with overall survival.'] |
['To explore the inhibitory effects of epigallocatechin gallate (EGCG) on the proliferation of colorectal cancer cells and on the gene expression of Notch signaling.', 'The colorectal cancer cells and orthotopic colorectal cancer transplant model were treated with EGCG, and MTT assay was used to test the inhibitory role of EGCG in the proliferation of colorectal cancer cells.', 'MTT assay indicated that EGCG inhibited the proliferation of these four cell lines when the time and concentration increased, and EGCG enhanced the apoptotic rate of these four cell lines. The dosage was positively correlated to the apoptotic rate, and EGCG inhibited the proliferation of colorectal cancer cells by influencing cell cycle. In-vivo study suggested that on the seventh day, the volume of tumors reduced after administrating with 5, 10 and 20 mg/kg of EGCG. At the twenty-eighth day, the volume of tumors was significantly different in three EGCG treatment groups as compared to the control group (P < 0.05), and TUNEL assay indicated that the apoptosis of cancer cells in EGCG treated groups was markedly higher than that in the control group (P < 0.05). In these cell lines, the expressions of HES1 and Notch2 in EGCG treated groups were remarkably lower than that in the control group (P < 0.05). The expression of JAG1 decreased in SW480 cells (P =0.019), HT-29 cells and HCT-8 cells, but increased in LoVo cells at mRNA level. The expression of Notch1 was upregulated in these four cell lines, but its expression was significantly upregulated only in LoVo and SW480 cells (P < 0.05).'] |
['Mast cells are prevalent in the shoulder of unstable atheromas; cardiac mast cells secrete proteases capable of activating matrix metalloproteinases. Histamine is essential in the inflammatory cascade of the unstable plaque. Ascorbate depletion has been correlated with histaminemia which has been shown to impair endothelial-dependent vasodilation. This study evaluates whether oxidative stress as measured by isoprostanes (PGF(2alpha)) coupled with an inflammatory state characterized by histaminemia predisposes patients to acute coronary syndrome (ACS).', 'Whole blood histamine, serum vitamin C, and serum PGF(2alpha) levels were drawn on 50 patients with ACS as determined by standard diagnostic criteria, 50 patients with stable coronary artery disease (SCAD), and 50 age and sex matched normal controls (C).', "Data were analyzed by stepwise discriminant and Spearman's rank correlation coefficient. A significant relationship exists between histamine and PGF(2alpha). As PGF(2alpha) rises above 60 pg/mL, an increase in histamine occurs in both the ACS and SCAD groups. A significant inverse relationship exists between ascorbate and histamine in the ACS versus C groups (P < 0.01) and the SCAD versus C groups (P < 0.01)."] |
['Stat3 is a member of the Janus-activated kinase/STAT signalling pathway. It normally resides in the cytoplasm and can be activated through phosphorylation. Activated Stat3 (p-Stat3) translocates to the nucleus to activate the transcription of several molecules involved in cell survival and proliferation. The constitutive activation of Stat3 has been shown in various types of malignancies, and its expression has been reported to indicate a poor prognosis. However, the correlation between the constitutive activation of Stat3 and the prognosis of cervical cancer patients has not been reported.', 'The immunohistochemical analysis of p-Stat3 expression was performed on tissues from 125 cervical squamous-cell carcinoma patients who underwent extended hysterectomy and pelvic lymphadenectomy, and the association of p-Stat3 expression with several clinicopathological factors and survival was investigated.', "Positive p-Stat3 expression was observed in 71 of 125 (56.8%) cases and was significantly correlated with lymph node metastasis, lymph vascular space invasion, and large tumour diameter (>4 cm) by Fisher's exact test. Kaplan-Meier survival analysis showed that p-Stat3 expression was statistically indicative of a poor prognosis for overall survival (P=0.006) and disease-free survival (P=0.010) by log-rank test."] |
['Examine the role of food spending behaviors and perceptions on fruit and vegetable intake among preadolescent children and their parents.', 'Cross-sectional study.', 'Metropolitan city.', 'Five hundred fifty-five parent/child dyads participating in the PARADE study. More than 50% of participants were African American and nearly 40% of households were low income.', "Body mass index calculated from child anthropometric data and parents' self-reported height and weight. Adult and child fruit and vegetable intake, annual household income, and food purchase behavior and perceptions obtained from parent questionnaire.", 'Analysis of variance used to identify differences in means at P<.05 level.', 'No statistically significant differences in fruit and vegetable intake by income status were observed. Children in households spending the least per week on groceries consumed fewer daily fruits and vegetables. Perceptions of cost of fruits and vegetables were also found to be significantly associated with fruit and vegetable intake among children and parents.'] |
['Therapeutic efficacy of intraperitoneal radioimmunotherapy is dependent on the time of retention of the radioimmunoconjugates within the peritoneal cavity. Therefore, the aim of this study was to investigate intraperitoneal retention of Fab, IgG and IgM radioimmunoconjugates.', 'Female Balb/c mice were injected with 213Bi- or 111In-labeled IgM, IgG and recombinant Fab conjugates intraperitoneally or intravenously. At different time points after injection, whole body distribution of radionuclides was imaged using a gamma camera. Distribution of radionuclides in selected organs was determined via γ-counting after sacrifice. Biological half-lives of the conjugates were calculated from whole body activities.', 'After i.p. injection 213Bi-Fab rapidly accumulated in the kidneys indicative of glomerular filtration and reabsorption. Accumulation of 213Bi-IgG in the kidneys was significantly lower. 213Bi-IgM showed a striking accumulation in the liver 180 min after i.p. injection. 111In-IgG persisted in the circulation up to 72 h both after i.p. and i.v. injection. 111In-IgM showed a continuous accumulation in the liver. Moreover, 111In-IgM was significantly higher 24 h after i.v. injection than i.p. injection both in liver and spleen. These differences could be confirmed via scintigraphy. After injection of 111In-IgG differences in scintigraphic images between i.v. and i.p. were clearly visible only at 3 h. Biological half lives were 24 h, 45 h and 165 h for 111In-IgM, 111In-Fab and 111In-IgG, respectively.'] |
["Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to improved management and husbandry practices, the availability of several anti-PCV2 vaccines provides an efficient immunological option for reducing the impact of these diseases. Most anti-PCV2 vaccines are marketed as injectable formulations. Although these are effective, there are problems associated with the use of injectable products, including laborious and time-consuming procedures, the induction of inflammatory responses at the injection site, and treatment-associated stress to the animals. Oral vaccines represent an improvement in antigen delivery technology; they overcome the problems associated with injection management and facilitate antigen boosting when an animals' immunity falls outside the protective window.", 'Chitosan microparticles were used as both a vehicle and mucosal adjuvant to deliver yeast-derived PCV2 virus-like particles (VLPs) in an attempt to develop an oral vaccine. The physical characteristics of the microparticles, including size, Zeta potential, and polydispersity, were examined along with the potential to induce PCV2-specific cellular immune responses in mice after oral delivery.', 'Feeding mice with PCV2 VLP-loaded, positively-charged chitosan microparticles with an average size of 2.5\xa0μm induced the proliferation of PCV2-specific splenic CD4+/CD8+ lymphocytes and the subsequent production of IFN-γ to levels comparable with those induced by an injectable commercial formulation.'] |
['The Dopamine D3 receptor (DRD3) gene is thought to be involved in essential hypertension (EH) because dopamine inhibits renin secretion via this receptor and because disruption of the DRD3 gene increases blood pressure in mice. EH is a complex, polygenetic disease. Association studies using the candidate gene approach may provide important clues regarding the etiology of hypertension and define a basis for further genetic investigation. Therefore we examined the association between the Ser9Gly polymorphism in the DRD3 gene and EH.', 'One hundred eighty-one patients with EH and 181 age-matched subjects with normal blood pressure were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction (PCR) was used to amplify the Ser9Gly polymorphic site in the DRD3 gene, and restriction fragment length polymorphism (RFLP) analysis of the PCR product was used to score the A and G alleles. Plasma renin activity and plasma aldosterone concentration were measured in untreated EH subjects.', 'The genotype distribution was in Hardy-Weinberg equilibrium, and was not significantly different between the NT and EH groups. The frequencies of A and G alleles were 0.674 (244/362) and 0.326 (118/362) for the NT group and 0.688 (249/362) and 0.312 (113/362) for the EH group, respectively, and did not differ significantly between the two groups. The genotype did not influence the plasma renin activity and aldosterone concentration in untreated EH patients.'] |
["Mutations in the gene ATP7B cause Wilson disease, a copper storage disorder with a high phenotypic and genetic heterogeneity. We aimed to evaluate whether 'severe' protein-truncating ATP7B mutations (SMs) are associated with low serum ceruloplasmin oxidase activities and an early age of onset when compared to missense mutations (MMs).", 'The clinical phenotype of 59 genetically confirmed WD patients was analyzed retrospectively. Serum ceruloplasmin was measured by its oxidase activity with o-dianisidine dihydrochloride as substrate and immunologically.', 'Thirty-nine patients had two MMs, 15 had the genotype SM/MM, and 5 patients had two SMs on their ATP7B alleles. Enzymatic and immunologic serum ceruloplasmin levels differed significantly between the three groups (P < 0.001 and P < 0.01, respectively). The lowest levels were measured in patients with two SMs (0.0 U/L; IQR, 0.0-0.0 U/L and 0.02 g/L; IQR, 0.01-0.02 g/L, respectively) and the highest in patients with two MMs (17.8 U/L; IQR, 5.8-35.1 U/L and 0.11 g/L; IQR,0.10-0.17 g/L, respectively). The age of onset was also significantly different between the three patient groups (P < 0.05), with SM/SM patients showing the earliest onset (13 years; IQR, 9-13 years) and patients with two MMs showing the latest onset (22 years; IQR, 14-27 years). By ROC curve analysis a ceruloplasmin oxidase level <or= 5 U/L can predict the presence of at least one SM with a sensitivity of 80% and a specificity of 79.5%.'] |
['Food in the upper gastrointestinal tract potentiates the glucose uptake response to insulin. Meal-induced insulin sensitization (MIS) occurs as a result of insulin-mediated release of hepatic insulin sensitizing substance (HISS) that increases glucose uptake in peripheral tissues. HISS release decreases with age, and exercise causes metabolic improvements in aging, therefore it is important to analyze the effect of exercise on age-associated decline in HISS-action.', 'The aim of this study is to test the hypothesis that improved insulin sensitivity, by voluntary running-wheel exercise in aging rats, is attained by preserving the HISS response. We also investigate the possible association of exercise-mediated beneficial changes in metabolic conditions and body composition with improved HISS-action.', 'We measured insulin- and HISS-sensitivity in 9, 14 and 21-week old rats with/without exercise. Metabolic markers were also determined in age-matched control and exercised rats.', 'Exercise significantly improved HISS-dependent glucose uptake in all age groups. The direct action of insulin was minimally altered by age or exercise. Body composition and metabolic conditions were beneficially changed with exercise-induced improvements in the HISS response.'] |
['Dexamethasone (Dex)-induced spontaneous tendon rupture and decreased self-repair capability is very common in clinical practice. The metaplasia of adipose tissue in the ruptured tendon indicates that Dex may induce tendon stem cells (TSCs) to differentiate into adipocytes, but the mechanism remains unclear. In the present study, we used in vitro methods to investigate the effects of Dex on rat TSC differentiation and the molecular mechanisms underlying this process.', 'First, we used qPCR and Western blotting to detect the expression of the adipogenic differentiation markers aP2 and C/EBPα after treating the TSCs with Dex. Oil red staining was used to confirm that high concentration Dex promoted adipogenic differentiation of rat TSCs. Next, we used qPCR and Western blotting to detect the effect of a high concentration of dexamethasone on molecules related to the canonical WNT/β-catenin pathway in TSCs.', 'Treating rat TSCs with Dex promoted the synthesis of the inhibitory molecule dickkopf1 (DKK1) at the mRNA and protein levels. Western blotting results further showed that Dex downregulated the cellular signaling molecule phosphorylated glycogen synthase kinase-3β (P-GSK-3 β (ser9)), upregulated P-GSK-3β (tyr216), and downregulated the pivotal signaling molecule β-catenin. Furthermore, DKK1 knockdown attenuated Dex-induced inhibition of the canonical WNT/β-catenin pathway and of the adipogenic differentiation of TSCs. Lithium chloride (LiCl, a GSK-3β inhibitor) reduced Dex-induced inhibition of the classical WNT/β-catenin pathway in TSCs and of the differentiation of TSCs to adipocytes.'] |
['GB virus C (GBV-C) coinfection is associated with reduced immune activation and a block in CD4(+) T-cell proliferation following interleukin-2 (IL-2) therapy in HIV-infected individuals. We examined peripheral blood mononuclear cells (PBMCs) from HIV-infected subjects with and without GBV-C viraemia to determine if GBV-C correlated with reactivation of latent HIV, T-cell proliferation or T-cell survival following in vitro activation with phytohaemagglutinin A and IL-2 (PHA/IL-2).', 'HIV-infected subjects whose HIV viral load was suppressed on combination antiretroviral therapy (cART) for >6 months were studied. PBMCs were cultured with and without PHA/IL-2 and monitored for HIV reactivation, proliferation and survival. GBV-C viraemia and in vitro replication were detected by real-time RT-PCR. HIV reactivation was determined by measuring HIV p24 antigen in culture supernatants. Proliferation was measured by counting viable cells and survival measured by flow cytometry.', 'Of 49 HIV-infected individuals, 26 had GBV-C viraemia. Significantly less HIV reactivation and PBMC proliferation following in vitro activation with PHA/IL-2 was observed in samples from GBV-C viraemic subjects compared with non-viraemic controls. Following 5 weeks in culture, GBV-C replication was associated with preservation of CD4(+) and CD8(+) T-cells compared with non-viraemic controls.'] |
['Co-ordinated cell movement is a fundamental feature of developing embryos. Massive cell movements occur during vertebrate gastrulation and during the subsequent extension of the embryonic body axis. These are controlled by cell-cell signalling and a number of pathways have been implicated. Here we use long-term video microscopy in chicken embryos to visualize the migration routes and movement behaviour of mesoderm progenitor cells as they emerge from the primitive streak (PS) between HH stages 7 and 10.', 'We observed distinct cell movement behaviours along the length of the streak and determined that this is position dependent with cells responding to environmental cues. The behaviour of cells was altered by exposing embryos or primitive streak explants to cell pellets expressing Wnt3a and Wnt5a, without affecting cell fates, thus implicating these ligands in the regulation of cell movement behaviour. Interestingly younger embryos were not responsive, suggesting that Wnt3a and Wnt5a are specifically involved in the generation of posterior mesoderm, consistent with existing mouse and zebrafish mutants. To investigate which downstream components are involved mutant forms of dishevelled (dsh) and prickle1 (pk1) were electroporated into the primitive streak. These had differential effects on the behaviour of mesoderm progenitors emerging from anterior or posterior regions of the streak, suggesting that multiple Wnt pathways are involved in controlling cell migration during extension of the body axis in amniote embryos.'] |
['Dental implant insertion torque is crucial for the success of the implant and the prosthesis. This in-vivo study was undertaken to determine the average insertion torque being applied to the dental implant while surgically placing it with a non-calibrated manual ratchet.', 'Three dental surgeons placed a total of 45 dental implants (Touareg, ADIN, Afula, Israel) in 42 selected patients. Each surgeon placed 15 implants. Standardised protocols were followed to prepare the site to place the dental implant. Each implant was placed using a manual non-calibrated implant ratchet first. Once the implant was nearly placed, a manual calibrated torque gauge ratchet was used to place the implant in its final position and at that instance, the maximum final torque applied was noted on the torque gauge scale.', 'The mean dental implant insertion torque applied by three surgeons using a non-calibrated manual ratchet was estimated to be 63.26\xa0Ncm with a standard error of 6.80 i.e. (63.26\xa0+\xa06.8), which was significantly higher than the baseline of 35\xa0Ncm (p\xa0<\xa00.0001). The mean dental implant torque applied by Surgeon 1, 2 and 3, respectively, was 65.93\xa0Ncm, 62.60\xa0Ncm and 62.13\xa0Ncm and this difference amongst them was found to be statistically insignificant (p\xa0>\xa00.05) and each of them had reached more than the baseline level of 35\xa0Ncm individually and significantly (p\xa0<\xa00.0001).'] |
['The receptor activator nuclear factor-kappaB ligand (RANKL) diffuses from articular cartilage to subchondral bone. However, the role of chondrocyte-synthesized RANKL in rheumatoid arthritis-associated juxta-articular bone loss has not yet been explored. This study aimed to determine whether RANKL produced by chondrocytes induces osteoclastogenesis and juxta-articular bone loss associated with chronic arthritis.', 'Chronic antigen-induced arthritis (AIA) was induced in New Zealand (NZ) rabbits. Osteoarthritis (OA) and control groups were simultaneously studied. Dual X-ray absorptiometry of subchondral knee bone was performed before sacrifice. Histological analysis and protein expression of RANKL and osteoprotegerin (OPG) were evaluated in joint tissues. Co-cultures of human OA articular chondrocytes with peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with macrophage-colony stimulating factor (M-CSF) and prostaglandin E2 (PGE2), then further stained with tartrate-resistant acid phosphatase.', 'Subchondral bone loss was confirmed in AIA rabbits when compared with controls. The expression of RANKL, OPG and RANKL/OPG ratio in cartilage were increased in AIA compared to control animals, although this pattern was not seen in synovium. Furthermore, RANKL expression and RANKL/OPG ratio were inversely related to subchondral bone mineral density. RANKL expression was observed throughout all cartilage zones of rabbits and was specially increased in the calcified cartilage of AIA animals. Co-cultures demonstrated that PGE2-stimulated human chondrocytes, which produce RANKL, also induce osteoclasts differentiation from PBMCs.'] |
["Adaptive statistical iterative reconstruction (ASIR) can decrease image noise, thereby generating CT images of comparable diagnostic quality with less radiation. The purpose of this study is to quantify the effect of systematic use of ASIR versus filtered back projection (FBP) for neuroradiology CT protocols on patients' radiation dose and image quality.", 'We evaluated the effect of ASIR on six types of neuroradiologic CT studies: adult and pediatric unenhanced head CT, adult cervical spine CT, adult cervical and intracranial CT angiography, adult soft tissue neck CT with contrast, and adult lumbar spine CT. For each type of CT study, two groups of 100 consecutive studies were retrospectively reviewed: 100 studies performed with FBP and 100 studies performed with ASIR/FBP blending factor of 40 %/60 % with appropriate noise indices. The weighted volume CT dose index (CTDIvol), dose-length product (DLP) and noise were recorded. Each study was also reviewed for image quality by two reviewers. Continuous and categorical variables were compared by t test and free permutation test, respectively.', 'For adult unenhanced brain CT, CT cervical myelography, cervical and intracranial CT angiography and lumbar spine CT both CTDIvol and DLP were lowered by up to 10.9 % (p\u2009<\u20090.001), 17.9 % (p\u2009=\u20090.005), 20.9 % (p\u2009<\u20090.001), and 21.7 % (p\u2009=\u20090.001), respectively, by using ASIR compared with FBP alone. Image quality and noise were similar for both FBP and ASIR.'] |
['The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. Full and abbreviated ribavirin area under the concentration time curves (AUC(0-12h), AUC(0-4h)) were derived from plasma concentration profiles at day 0 (D0), week 12 (W12), W12 + 1 day, and W24. Virological follow-up was performed at D0 (0, 12, and 24 hours), W2, W4, W6, and monthly until W72 (TaqMan polymerase chain reaction, cut-off 15 international units/mL). Twenty-eight patients were enrolled in the study and 24 completed it. Patients with a SVR had a significantly higher D0 AUC(0-12h) (3695 [1571-6916] versus 2937 [1266-4913] microg/hour/L, P = 0.03) and D0 AUC(0-4h) (2010 [615-3175] versus 1340 [622-2246] microg/hour/L, P = 0.03). Patients with D0 AUCs above the cut-off values defined by receiver operating characteristic curves (3014 microg/hour/L and 1755 microg/hour/L for AUC(0-12h) and AUC(0-4h), respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio = 16.0, 95% confidence interval 1.54-166.6, P = 0.02 and odds ratio = 8.9, 95% confidence interval, 1.4-56.6; P = 0.02).'] |
['Whether or not the deleted in colorectal cancer (DCC) gene is implicated in metastases or in predicting prognosis in patients with colorectal cancer has not previously been substantiated. Our aims were to investigate DCC expression in primary colorectal cancers and in metastases to identify any prognostic significance.', 'DCC expression was examined immunohistochemically in 195 primary colorectal adenocarcinomas and in 23 paired primary tumors and lymph node metastases. DNA content and S-phase fraction were measured by flow cytometry.', 'The absence of DCC expression was observed in 55 primary tumors (28%). DCC negativity was significantly related to poor prognosis in patients with DNA diploid tumors (P =.03) and those with a low S-phase fraction (< 5%, P =.02) but not in patients with nondiploid tumors or those with a higher S-phase fraction. Furthermore, DCC expression retained its prognostic significance in the diploid subgroup after adjusting for sex, age, site, stage, growth pattern, and differentiation (P =.01). DCC expression was similar in primary tumors and their metastases.'] |
['Massive pulmonary embolism (MPE) is a significant cause of mortality and, with submassive pulmonary embolism (SPE), is associated with chronic thromboembolic pulmonary hypertension, resulting in ongoing patient morbidity. Standard treatment is anticoagulation, although systemic thrombolytic therapy has been shown to reduce early mortality in patients with MPE and improve cardiopulmonary hemodynamics in patients with SPE. However, systemic lysis is associated with significant bleeding risk. Early reports of catheter-directed techniques (CDT) suggest favorable outcomes in patients with MPE and SPE with reduced risk of hemorrhage. The purpose of this study is to evaluate efficacy and safety outcomes in MPE and SPE patients treated with CDT.', 'Seventeen patients treated with CDT for MPE and SPE were clinically and hemodynamically evaluated. Patients were grouped by severity of pulmonary embolism: MPE (n\xa0=\xa05) or SPE (n\xa0=\xa012). Pre- and post-interventional measures were assessed, including pulmonary artery pressures (PAPs), cardiac biomarkers, tricuspid regurgitation, right ventricular (RV) dilatation, and systolic function. Nine patients had contraindications to systemic thrombolytic therapy.', 'PAP was elevated in 94% at presentation. The average dose of recombinant tissue plasminogen activator (rt-PA) was 31\xa0mg; 44\xa0mg in MPE and 26\xa0mg in SPE. Pre- and post-intervention PAPs were recorded in 13 patients. All demonstrated an acute reduction in posttreatment PAP, averaging 37%. At presentation, all MPE and 10 (83%) SPE patients showed both RV dilatation and reduced function on echocardiography, which normalized in 76% (13/17) and improved in 24% (4/17) after CDT. Patients who demonstrated left ventricle underfilling before CDT (2 [40%] MPE and 2 [20%] SPE) normalized after CDT. All MPE and 11 (92%) SPE patients had tricuspid regurgitation on echocardiography pretreatment, which resolved in 60% and 58% of MPE and SPE patients, respectively. One delayed mortality occurred in an MPE patient who was hypotensive and hypoxic at presentation. There was one puncture site bleed.'] |
['We aimed to quantify concentrations of inducible heme oxygenase (HO)-1 in the lungs of patients with acute respiratory distress syndrome (ARDS) and to investigate its role as a source of ferrous iron and as a signaling agent for iron regulation. Control of such processes by heme oxygenase has implications for the onset, progression, and resolution of ARDS.', 'Retrospective analysis of archived samples.', 'Adult intensive care unit of a postgraduate teaching hospital.', 'Patients admitted to the adult intensive care unit who fulfilled the American-European Consensus Conference criteria for ARDS.', 'Biochemical and immunohistochemical studies using bronchoalveolar lavage fluid or lung tissue were performed in patients with established ARDS and in those undergoing lung resection (controls).', 'Concentrations of heme oxygenase protein were significantly elevated in lung tissue (193.7 +/- 13.27 vs. 81.0 +/- 16.0%, p < .01) and in bronchoalveolar lavage fluid (2.4 x 10(5) vs. 1.4 x 10(5) densitometric units, p = .047) taken from patients with ARDS compared with controls. Concentrations of heme oxygenase protein in bronchoalveolar lavage fluid from patients with ARDS correlated positively and significantly with changes in the concentrations of ferritin (r = .697, p = .02) and the iron saturation of transferrin (r = .8, p = .014) but correlated negatively and significantly with concentrations of bleomycin-detectable (redox-active) iron (r = -.73, p = .031). Significantly elevated (p < .05) concentrations of heme oxygenase staining in cell types expressing this protein were detected in patients with ARDS, compared with concentrations in the same cells taken from controls undergoing lung resection.'] |
["The aim of the study was to investigate, using a native mitomycin-C-resistant human Tenon's fibroblast cell line, the possibility that interferon-alpha and gamma could be used with Fas agonists as an alternative anti-fibrotic strategy to mitomycin-C in trabeculectomy.", "A clinically resistant and in vitro verified mitomycin-C-resistant human Tenon's fibroblast cell line was pretreated with interferon-alpha and interferon-gamma for 48\u2009h before stimulation with an agonistic Fas antibody (CH11) for 2 days to induce cell death. Cell death assays were undertaken. Changes in apoptosis-related proteins were determined by flow cytometry and Western blot.", "Pretreatment with interferon-alpha or interferon-gamma for 48\u2009h increased Fas, Fas-associated protein with death domain and caspase-8 expression. Protein expression was further increased by combined exposure to interferon-alpha and gamma. Pretreatment with cytokines had no effect on Fas-L and Bcl-2. Interferon-alpha alone did not change the rate of induced cell death. A combination of interferon-alpha and gamma synergistically increased the sensitivity of mitomycin-C-resistant human Tenon's fibroblast cell line to induced cell death. An antagonistic anti-Fas antibody (ZB4) completely blocked induced cell death. Broad caspase inhibitors specific for caspases-8 and -3 reduced induced deaths in interferon pretreated mitomycin-C-resistant human Tenon's fibroblast cell line in a dose-dependent manner."] |
['The insertion/deletion polymorphism of angiotensin-converting enzyme may influence muscle properties. We examined whether Pompe disease clinical manifestations, which are known to be highly variable among late-onset patients, may be modulated by angiotensin-converting enzyme polymorphism.', 'We included 38 patients with late-onset Pompe disease, aged 44.6 +/- 19.8 years. We compared the distribution of angiotensin-converting enzyme polymorphism according to demographic and disease parameters.', 'The distribution of angiotensin-converting enzyme polymorphism was in line with the general population, with 16% of patients carrying the II genotype, 37% carrying the DD genotype, and the remaining patients with the ID genotype. The three groups did not differ in mean age, disease duration, Walton score, and other scores used to measure disease severity. The DD polymorphism was associated with earlier onset of disease (P = 0.041), higher creatine kinase levels at diagnosis (P = 0.024), presence of muscle pain (P = 0.014), and more severe rate of disease progression (P = 0.037, analysis of variance test for interaction).'] |
['Genetic variation in both the composition and distribution of fat and muscle in the body is important to human health as well as the healthiness and value of meat from cattle and sheep. Here we use detailed phenotyping and a multi-trait approach to identify genes explaining variation in body composition traits.', 'A multi-trait genome wide association analysis of 56 carcass composition traits measured on 10,613 sheep with imputed and real genotypes on 510,174 SNPs was performed. We clustered 71 significant SNPs into five groups based on their pleiotropic effects across the 56 traits. Among these 71 significant SNPs, one group of 11 SNPs affected the fatty acid profile of the muscle and were close to 8 genes involved in fatty acid or triglyceride synthesis. Another group of 23 SNPs had an effect on mature size, based on their pattern of effects across traits, but the genes near this group of SNPs did not share any obvious function. Many of the likely candidate genes near SNPs with significant pleiotropic effects on the 56 traits are involved in intra-cellular signalling pathways. Among the significant SNPs were some with a convincing candidate gene due to the function of the gene (e.g. glycogen synthase affecting glycogen concentration) or because the same gene was associated with similar traits in other species.'] |
['Cardiac amyloidosis (CA) is the most problematic cause of heart failure because medical treatment strategies are not well tolerated. Due to its high mortality, identification of patients at high risk is crucial for treatment strategies such as heart transplantation prior to chemotherapy for amyloid disease.', 'Left ventricular wall thickness (LVT) progression was retrospectively compared with electrocardiographic and echocardiographic parameters for risk prediction in 39 patients with histologically proven cardiac amyloidosis.', 'Seventeen deaths occurred, equivalent to 1- and 3-year survival rates of 62.1% and 55.0%, respectively. LVT progression in deceased patients was 2.02 +/- 0.85 mm/month compared with 0.19 +/- 0.03 mm/month in survivors (p < 0.001). Autologous stem-cell transplantation (n = 22, or 54%) reduced LVT progression as compared with not receiving stem cells (0.21 +/- 0.04 mm/month vs 1.45 +/- 0.57 mm/month, p < 0.005). LVT progression correlated with maximal LVT and absolute LVT increase. Progression of LVT was more rapid in patients with impaired LV ejection fraction (LVEF) than preserved LVEF (2.16 +/- 1.04 mm/month vs 0.30 +/- 0.13 mm/month, p < 0.001). LVT closely correlated with survival, whereas initial, maximum or absolute increase in LVT did not. Further predictors of survival were LVEF, autologous stem-cell transplantation and low voltage, but not diastolic dysfunction. Multivariate analysis identified LVT progression as the strongest independent parameter for survival.'] |
["Apolipoprotein-E (apoE) ε4 allele is a known risk factor for Alzheimer's disease (AD). Polymorphism of apoE is also one of the most important genetic markers for coronary artery disease (CAD). The allelic variation in the apoE gene has a significant effect on inter-individual variation of lipids and lipoprotein plasma levels as well. This study investigated whether apoE polymorphism affects the plasma levels of apoE and the possible association to CAD extent and cognitive functions.", 'Plasma apoE levels and apoE genotypes were evaluated of subjects with normal coronary arteries, and individuals with angiographycally confirmed mild/moderate or severe atheromatosis. The cognitive performance of the volunteers was also measured by mini-mental state examination (MMSE).', 'Out of the 6 expected genotypes, only 5 were detected in participants: E3/3 (56.0%), E3/4 (23.6%), E4/4 (8.2%), E2/4 (3.3%), E2/3 (8.9%). The ε3 allele (72%) was the most frequent, followed by ε4 (22%) and ε2 (6%). No difference was found in plasma levels of either apoE or in apoE genotype frequencies among the groups, however MMSE scores of CAD patients irrespective of their atheromatosis extent were significantly lower than that seen in the normal population.'] |
['Hyperglycemia on admission is associated with increased mortality rates in patients with ST-elevation myocardial infarction (STEMI) who are treated with either fibrinolytic therapy (FT) or primary percutaneous coronary intervention (PCI). However, data regarding the relationship between hyperglycemia and the success of FT are lacking. The aim of this study was to investigate the value of admission blood glucose for the prediction of failed reperfusion following FT.', 'This is a retrospective study of 304 STEMI patients who received FT and whose admission glucose levels were recorded. The main outcome measure was ST segment resolution≥50%. The median (interquartile range [IQR]) blood glucose level in the entire study group was 112 (95-153). In 92 (30.2%) patients, FT was unsuccessful and rescue PCI was performed. Admission glucose (126 [99-192] vs. 110 [94-144] mg/dL, p<0.001), time from symptom onset to FT (180 [120-270] vs. 150 [120-180] min, p=0.009), and maximum ST elevation amplitude (3 [2-7] vs. 3 [2-6] mm, p=0.05) were higher in the failed reperfusion group than in the reperfusion group. Admission hyperglycemia was an independent predictive factor for failed reperfusion (hazard ratio 4.79 [1.80-12.76], p=0.002), along with time from symptom onset to fibrinolysis and anterior wall myocardial infarction.'] |
['Heritable risk for breast cancer includes an increasing number of common, low effect risk variants. We conducted a multistage genetic association study in a series of independent epidemiologic breast cancer study populations to identify novel breast cancer risk variants.', 'We tested 1,162 SNPs of greatest nominal significance from stage I of the Cancer Genetic Markers of Susceptibility breast cancer study (CGEMS; 1,145 cases, 1,142 controls) for evidence of replicated association with breast cancer in the Nashville Breast Cohort (NBC; 599 cases, 1,161 controls), the Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls), and BioVU Breast Cancer Study (BioVU; 1,172 cases, 1,172 controls).', 'Among these SNPs, a series of validated breast cancer risk variants yielded expected associations in the study populations. In addition, we observed two previously unreported loci that were significantly associated with breast cancer risk in the CGEMS, NBC, and CBCS study populations and had a consistent, although not statistically significant, risk effect in the BioVU study population. These were rs1626678 at 10q25.3 near ENO4 and KIAA1598 (meta-analysis age-adjusted OR = 1.13 [1.07-1.20], P = 5.6 × 10(-5)), and rs8046508 at 16q23.1 in the eighth intron of WWOX (meta-analysis age-adjusted OR = 1.20 [1.10-1.31], P = 3.5 × 10(-5)).'] |
['Necrotizing enterocolitis (NEC) is an important cause of mortality and morbidity in preterm infants.', 'To evaluate the effect of maternal preeclampsia on the development and severity of NEC in premature infants.', 'Prospective observational study in a tertiary neonatal intensive care unit.', 'The preterm infants of ≤ 37 gestational age who were consecutively hospitalized were enrolled. The study group contained preterm infants born to a preeclamptic mother and the comparison group contained preterm infants born to a normotensive mother.', 'The primary outcome was to determine the association between preeclampsia and NEC.', 'A total of 88 infants had NEC diagnosis. The incidence of NEC in infants born to preeclamptic mothers (22.9%) was significantly higher compared with those born to normotensive mothers (14.6%). According to NEC stages, NEC was more advanced in preeclamptic mother infants. NEC developed significantly earlier in infants with NEC in the study group. The duration of NEC was also significantly longer in infants born to preeclamptic mothers. In multiple logistic regression model, preeclampsia was found to be predictive of NEC with an odds ratio of 1.74 (95% confidence interval 0.64-0.92).'] |
["The present study was designed to decipher molecular mechanisms underlying nicotine's promoting atrial fibrillation (AF) by inducing atrial structural remodelling.", 'The canine model of AF was successfully established by nicotine administration and rapid pacing. The atrial fibroblasts isolated from healthy dogs were treated with nicotine. The role of microRNAs (miRNAs) on the expression and regulation of transforming growth factor-beta1 (TGF-beta1), TGF-beta receptor type II (TGF-betaRII), and collagen production was evaluated in vivo and in vitro. Administration of nicotine for 30 days increased AF vulnerability by approximately eight- to 15-fold in dogs. Nicotine stimulated remarkable collagen production and atrial fibrosis both in vitro in cultured canine atrial fibroblasts and in vivo in atrial tissues. Nicotine produced significant upregulation of expression of TGF-beta1 and TGF-betaRII at the protein level, and a 60-70% decrease in the levels of miRNAs miR-133 and miR-590. This downregulation of miR-133 and miR-590 partly accounts for the upregulation of TGF-beta1 and TGF-betaRII, because our data established TGF-beta1 and TGF-betaRII as targets for miR-133 and miR-590 repression. Transfection of miR-133 or miR-590 into cultured atrial fibroblasts decreased TGF-beta1 and TGF-betaRII levels and collagen content. These effects were abolished by the antisense oligonucleotides against miR-133 or miR-590. The effects of nicotine were prevented by an alpha7 nicotinic acetylcholine receptor antagonist.'] |
['Determine if recruitment methods are differentially related to the reach of a physical activity program in metro/urban vs. rural settings.', 'Cross-sectional survey.', 'Kansas counties.', 'Ninety-four Cooperative Extension agents responsible for 102 counties.', 'Promotional score, task force activity, and years of program delivery were assessed using a self-report survey. Reach was assessed for each county by dividing the number of participants by intended population using census data.', 'Rural/urban comparisons on reach were completed using a Mann-Whitney test. Multiple linear regression models were used to determine the relationship between independent variables and participation rate by setting type.', 'Metro/urban counties had lower mean participation rates than rural counties (z = -4.5; p < .001). In metro/urban counties, the regression on participation rate was significant (R(2) = .19; F = 4.09; p = .011), but only promotional score significantly contributed to the model (p = .003). In rural counties, the regression was also significant (R(2) = .34; F = 6.64; p = .001), with task force activity and years of delivery making significant contributions (p = .001 and p = .017, respectively).'] |
['The main aim of this study was to verify the effect of natalizumab on the levels of circulating catecholamines and indolamine and their possible relation with MS.', "For this purpose, 12 healthy individuals (control group) and 12 relapsing-remitting multiple sclerosis patients (RR-MS) were selected. The patients were treated with 300 mg of natalizumab during 56 weeks (1 dose/4 weeks) (MS-56). This selection was based on the McDonalds revision criterion and scheduled to star treatment with natalizumab. Blood samples were taken before treatment (basal level) and after 56 weeks of using natalizumab. Melatonin was measured in serum and in plasma, catecholamines (dopamine, epinephrine, and norepinephrine), carbonylated proteins, 8-hydroxy-2'deoxyguanosine (8OH-dG) and the ratio reduced glutathione/oxidised glutathione (GSH/GSSG).", 'The epinephrine and dopamine levels diminished in the basal group with respect to the control and did not recover normal levels with the treatment. The melatonin was decreased in RR-MS patients and went back to its normal levels with natalizumab. Norepinephrine was increased in RR-MS and decreased in MS-56 until it equalled the control group.'] |
['Natural killer T (NKT) cells share phenotypic and functional properties with both conventional natural killer cells and T cells. These cells might have an important role in the pathogenesis of ulcerative colitis (UC). The interaction of chemokine ligand 25 (CCL25) with chemokine receptor 9 (CCR9) is involved in gut-specific migration of leukocytes and induces regulatory T cells (Tregs) to migrate to the intestine in chronic ileitis.', 'In UC patients, NKT receptor CD161, CCL25, and CCR9 expression levels were evaluated by qRT-PCR. A murine model of oxazolone-induced colitis was induced in BALB/c mice. The mRNA levels of NK1.1, CCL25 and CCR9, and pro-inflammatory cytokines in mice were evaluated. The CCR9 expression on Type I or invariant NKT (iNKT) cells, and the iNKT cells chemotaxis are observed according to flow cytometry. NKT receptor CD161, CCL25 and CCR9 expression levels were significantly increased in UC patients. And, the mRNA expression levels of NK1.1, CCL25 and CCR9 were increased in oxazolone-induced colitis in mice. The production of pro-inflammatory cytokines was significantly increased, especially interleukin 4 (IL-4), IL-10 and IL-13. We observed significantly increased CCR9 expression on iNKT cells. Furthermore, we found an increased iNKT population and enhanced chemotaxis during oxazolone-induced colitis.'] |
['The amygdala has been strongly implicated in the processing of threat-relevant information in specific phobia. However, there is an ongoing debate as to whether the amygdala may also be engaged outside of conscious stimulus awareness. Furthermore, considering that sustained vigilance for threat constitutes a crucial characteristic of specific phobias, we hypothesized a possible role of this symptom in modulating amygdala sensitivity to disorder-relevant cues. Using event-related functional magnetic resonance imaging, we examined responses of the amygdala to subliminal and supraliminal phobogenic stimuli in spider-phobic subjects and whether these responses might be specifically associated with disorder-related hypervigilance.', "Eighteen female spider-phobic subjects and 18 healthy female control subjects were exposed to pictures of spiders and phobia-irrelevant objects, presented briefly during two backward-masking conditions used to manipulate stimulus awareness. Brain activation data were analyzed as a function of subjects' perceptual performance on each single trial and were tested for correlations with different components of the phobic symptomatology, such as vigilance, as assessed by self-report scales.", 'Compared with control subjects, phobic participants showed stronger responses of both amygdalae to consciously perceived spiders versus nonspider targets, whereas during unconscious stimulus processing, enhanced activation was only apparent in the right amygdala. Moreover, the intensity of disorder-related vigilance was positively correlated with right amygdala activation specifically during the subliminal condition.'] |
['Acute pancreatitis is a severe disease with unpredictable course and outcomes. It is especially hard to identify early those patients who will have a fulminant course. In a prospective observational study, we tested the hypothesis that the CT Severity Index (CTSI), established within 48hours after admission, is prognostic for morbidity and mortality and can predict the necessity for admission to an ICU.', 'From January 1994 to October 2002, all patients with the diagnosis of first time acute pancreatitis underwent spiral CT with intravenous contrast within 48hours of admission. The extent of inflammation and necrosis was assessed to define the CTSI. Patients were initially managed in an ICU in a standardized fashion. Complications and mortality were registered in a systematic manner.', 'Seventy-nine patients were admitted with acute pancreatitis. The overall complication rate was 57%; mortality was 9%. In patients with a CTSI of 0 to 3, these rates were 42% and 2%, respectively; in those with CTSI of 4 to 6, 81% and 19%, respectively; and in those with CTSI of 7 to 10, 100% and 33%, respectively. Outcomes of subsequent CT scans did not alter the initial prognosis. Early CTSI correlated well with the incidence of complications, sepsis, mortality, and necessity for ICU admission.'] |
['To quantify functional age-related changes in the cartilage antioxidant network in order to discover novel mediators of cartilage oxidative stress and osteoarthritis (OA) pathophysiology.', 'We evaluated histopathologic changes of knee OA in 10-, 20-, and 30-month-old male F344BN rats and analyzed cartilage oxidation according to the ratio of reduced to oxidized glutathione. Antioxidant gene expression and protein abundance were analyzed by quantitative reverse transcription-polymerase chain reaction and selected reaction-monitoring mass spectrometry, respectively. Superoxide dismutase 2 (SOD2) activity and acetylation were analyzed by colorimetric enzyme assays and Western blotting, respectively. We examined human OA cartilage to evaluate the clinical relevance of SOD2 acetylation, and we tested age-related changes in the mitochondrial deacetylase sirtuin 3 (SIRT-3) in rats and mice.', 'Cartilage oxidation and OA severity in F344BN rats increased with age and were associated with an increase in SOD2 expression and protein abundance. However, SOD2-specific activity decreased with age due to elevated posttranslational lysine acetylation. Consistent with these findings, SIRT-3 levels decreased substantially with age, and treatment with SIRT-3 increased SOD2 activity in an age-dependent manner. SOD2 was also acetylated in human OA cartilage, and activity was increased with SIRT-3 treatment. Moreover, in C57BL/6J mice, cartilage SIRT-3 expression decreased with age, and whole-body deletion of SIRT-3 accelerated the development of knee OA.'] |
['It is currently unclear whether the expression of HOX transcript antisense RNA (HOTAIR) correlates with the progression of esophageal cancer. The aim of this study was to examine HOTAIR expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance.', 'Differences in the expression of HOTAIR were examined via in situ hybridization (ISH) and quantitative reverse transcriptase PCR (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Proliferation, colony formation and migration assays were performed in ESCC cell lines to determine the function of HOTAIR in the progression of ESCC in vitro.', 'A notably higher level of HOTAIR expression was found in ESCC tissues. High expression levels of HOTAIR in ESCC patients correlated positively with clinical stage, TNM classification, histological differentiation and vital status. HOTAIR expression was found to be an independent prognostic factor in ESCC patients. ESCC patients who expressed high levels of HOTAIR had substantially lower overall 5-year survival rates than HOTAIR-negative patients. In vitro assays of ESCC cell lines demonstrated that HOTAIR mediated the proliferation, colony formation and migratory capacity of ESCC cells.'] |
['Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric mucosa. Previous studies have shown that the proinflammatory cytokine interleukin (IL)-1beta present during chronic gastritis inhibits histamine synthesis in ECL cells and leads to sustained functional impairment. This study investigated the effects of IL-1beta on ECL cell apoptosis and the related signal-transduction mechanisms.', 'ECL cells were isolated by pronase digestion and a combination of elutriation, gradient centrifugation, and 48-hour culture (purity >/=90%). Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling reaction and cell death detection enzyme-linked immunosorbent assay.', 'IL-1beta (100 pg/mL) increased the rate of programmed cell death 2-3 fold in ECL cells after 24 hours of incubation (total of 12%-14%). This effect was completely inhibited by the NF-kappaB inhibitor, proteasome inhibitor I, and the nitric oxide synthase inhibitor (iNOS) N(G)-monomethyl-L-arginine (10(-4) mol/L), but not by the caspase 3 inhibitor, Asp-Glu-Val-Asp-CHO. Western blot analysis, reverse-transcription polymerase chain reaction (PCR), and in situ PCR showed that IL-1beta induced gene expression (after 2-4 hours) and protein synthesis (6-18 hours) of the iNOS isoform in ECL cells. Bax protein expression was increased in response to IL-1beta. In contrast, bcl-2 gene expression was increased in response to basic fibroblast growth factor, which has been shown to counteract IL-1beta- induced apoptosis.'] |
['Altered epidermal barrier function as determined by transepidermal water loss (TEWL) is a typical feature in patients with atopic eczema (AE).', 'The purpose of this study was to assess the kinetics of epidermal regeneration after barrier perturbation induced by two different stimuli, namely acetone treatment (removal of stratum corneum lipids) and tape stripping (removal of the nonviable stratum corneum).', 'Fifteen patients with AE and 12 nonatopic healthy controls were investigated. An area of 9.0 cm2 of clinically normal skin of the forearm flexural side was treated by acetone or tape stripping in a way that an increase in TEWL of 3.5-4.0 times the pretreatment value was achieved. TEWL was recorded directly after perturbation (tO), after 15 min (tl), 3 h (t2), 6 h (t3), 24 h (t4), 48 h (t5), 72 h (t6) and 96 h (t7).', 'The speed of epidermal regeneration was faster after acetone treatment, both in the patient and the control groups, with no significant difference between the two. However, after tape stripping at points t2, t5 and t6, TEWL values relative to tO were significantly lower in atopic skin as compared to normal skin (p < 0.05).'] |
['Epinephrine given during closed-chest resuscitation increases blood flow across the coronary and cerebral circuits. However, epinephrine worsens reperfusion arrhythmias and intensifies postresuscitation myocardial dysfunction. We investigated whether cariporide-a selective sodium-hydrogen exchanger isoform-1 inhibitor-could ameliorate such adverse effects without diminishing its vasopressor actions.', 'Randomized animal study.', 'University-based animal laboratory.', 'Twenty-four anesthetized male domestic pigs (29-43 kg).', 'Ventricular fibrillation was electrically induced and left untreated for 8 mins. Pigs were randomized to receive after 2 mins of chest compression a 3 mg/kg bolus of cariporide (n = 8), a 0.02 mg/kg bolus of epinephrine (n = 8), or a combination of cariporide and epinephrine (n = 8). Additional doses of epinephrine were given if the coronary perfusion pressure decreased below 15 mm Hg. Successfully resuscitated pigs were observed for 72 hrs.', 'The averaged coronary perfusion pressure was higher in the epinephrine (34 +/- 11 mm Hg, p = .001) and cariporide/epinephrine (35 +/- 10 mm Hg, p < .001) groups compared with the cariporide group (15 +/- 6 mm Hg). All pigs in the epinephrine and cariporide/epinephrine groups but only six in the cariporide group were successfully resuscitated and survived 72 hrs. During the immediate postresuscitation period, four of eight pigs in the epinephrine group had episodes of recurrent ventricular fibrillation or pulseless ventricular tachycardia requiring additional electrical shocks (7.0 +/- 6.4) but none in the cariporide and cariporide/epinephrine groups (chi-square, p = .008). Myocardial dysfunction occurred early after return of spontaneous circulation but only in the epinephrine group.'] |
['Postoperative pain is a common problem in male circumcision. We investigated the effect of nanometer silver dressing (Shenzhen AGT Pharm. Co. Ltd.) in relieving pain following male circumcision.', 'Sixty patients undergoing circumcision in the outpatient department were randomized into an experimental and a control group, the incision covered with nanometer silver dressing in the former and with vaseline dressing in the latter. None of the patients received any analgesics or other pain-killing therapies after surgery. The postoperative pain intensity was accessed using the modified numeric pain intensity assessment scale at 1, 2, 3, 5 and 7 days after the operation, and statistical analyses were performed using SPSS 12.0 software.', "The patients averaged (31.13 +/- 13.94) years in age, and had no significant differences in age and body mass index (BMI) between the two groups. At 1, 2, 3 and 5 days, postoperative pain intensity was significantly lower in the experimental than in the control group (P > 0.05). Multiple regression analysis revealed that postoperative pain score was not correlated with patients' age, BMI and types of disease, but with the types of dressing."] |
['Osteosarcoma (OS), which has a high potential for developing metastatic disease, is the most frequent malignant bone tumor in children and adolescents. Molecular analysis of a metastatic genetically engineered mouse model of osteosarcoma identified enhanced expression of Secreted Frizzled-Related Protein 2 (sFRP2), a putative regulator of Wnt signaling within metastatic tumors. Subsequent analysis correlated increased expression in the human disease, and within highly metastatic OS cells. However, the role of sFRP2 in osteosarcoma development and progression has not been well elucidated.', 'Studies using stable gain or loss-of-function alterations of sFRP2 within human and mouse OS cells were performed to assess changes in cell proliferation, migration, and invasive ability in vitro, via both transwell and 3D matrigel assays. In additional, xenograft studies using overexpression of sFRP2 were used to assess effects on in vivo metastatic potential.', 'Functional studies revealed stable overexpression of sFRP2 within localized human and mouse OS cells significantly increased cell migration and invasive ability in vitro and enhanced metastatic potential in vivo. Additional studies exploiting knockdown of sFRP2 within metastatic human and mouse OS cells demonstrated decreased cell migration and invasion ability in vitro, thus corroborating a critical biological phenotype carried out by sFRP2. Interestingly, alterations in sFRP2 expression did not alter OS proliferation rates or primary tumor development.'] |
['The mechanisms underlying the aggravation or development of hypertension frequently seen during treatment of renal anemia with epoetins are not fully elucidated. The aim of the present study was to investigate the effects of epoetin alfa on endothelial vasodilatory function in patients with renal anemia and in healthy subjects.', 'Eighteen preuremic patients with anemia (GFR 23.4 +/- 11 SD ml/min, Hb 101 +/- 8 g/l) and 10 healthy subjects underwent evaluation of endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIDV) by means of forearm blood flow (FBF) measurements with venous occlusion plethysmography during local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). These investigations were performed before and 30 min after an intravenous injection of epoetin alfa (10,000 IU). Ten healthy subjects underwent the same procedure with the exception that saline were given instead of epoetin. The patients were treated with epoetin alfa subcutaneously for 12-19 weeks and reevaluated when Hb exceeded 120 g/l.', 'EDV was attenuated after the epoetin injection in both renal patients and healthy subjects. This impairment persisted after anemia had been treated. EDIV and blood pressure remained constant. Saline had no effect on the variables measured.'] |
['Controlled laboratory study.', 'The hip abductor muscles are important hip joint stabilizers. Hip joint pain may alter muscle recruitment. Motion-mode (M-mode) ultrasound enables noninvasive measurements of the onset of deep and superficial muscle motion, which is associated with activation onset.', 'To compare (1) the onset of superficial and deep gluteus medius and gluteus minimus muscle motion relative to the instant of peak ground reaction force and (2) the level of swing-phase muscle motion during step-down between subjects with chronic hip pain and controls using M-mode ultrasound.', 'Thirty-five subjects with anterior, nontraumatic hip pain for more than 6 months (mean ± SD age, 54 ± 9 years) and 35 controls (age, 57 ± 7 years) were scanned on the lateral hip of the leading leg during frontal step-down onto a force platform using M-mode ultrasound. Computerized motion detection with the Teager-Kaiser energy operator was applied on the gluteus minimus and the deep and superficial gluteus medius to determine the time lag between muscle motion onset and instant of peak ground reaction force and the level of gluteus minimus motion during the swing phase. Time lags and motion levels were averaged per subject, and t tests were used to determine between-group differences.', 'In participants with hip pain, gluteus minimus motion onset was 103 milliseconds earlier (P = .002) and superficial gluteus medius motion was 70 milliseconds earlier (P = .047) than those in healthy control participants. The level of gluteus minimus swing-phase motion was higher with pain (P = .006).'] |
['The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection.', 'Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n = 18), HIV subjects treated with antiretroviral medications (HIV+ARV, n = 12), or not treated with antiretroviral medications (HIV+NARV, n = 12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging.', 'HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to SN (p-corrected = 0.006). HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected = 0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs.'] |
['Guttate psoriasis (GP) is characterized by acute onset of small, rounded psoriatic lesions. Although this particular phenotype of psoriasis is usually associated with streptococcal throat infections and mainly occurs in HLA-Cw6(+) patients, the specific immunologic response to this innate stimulus that causes these skin lesions is poorly understood.', 'This study aims to elucidate how key cellular elements of patients with GP respond to Streptococcus pyogenes and whether this initial immune response is favored by the genetic and environmental background of these patients.', 'Circulating memory T\xa0cells and autologous epidermal cells from samples from either patients with GP (n\xa0=\xa014) or healthy control subjects (n\xa0=\xa06) were cocultured ex\xa0vivo in the presence of an S pyogenes extract. Levels of the psoriasis-associated cytokines IL-17A, IL-17F, IFN-γ, TNF-α, IL-6, and IL-8 were determined. The expression of several genes with increased (DEFB4, S100A7, LCN2, IL36G, IL8, CXCL9, CXCL10, and CXCL11)\xa0or decreased (FLG and LOR) transcripts in psoriatic lesions was examined in keratinocytes treated with coculture supernatants.', 'When skin-homing effector memory cutaneous lymphocyte antigen-positive T\xa0cells were used in cocultures, a\xa0TH17-dominant response was observed, as reflected by the higher amounts of IL-17A and IL-17F than IFN-γ. Moreover, a higher TH17 response was observed in cells isolated from patients with flares associated with a streptococcal tonsillitis and with the HLA-Cw6 allele (cohort 1). In addition, in normal keratinocytes the supernatants from these cocultures induced an increase in IL-17-associated genes, such as DEFB4, S100A7, LCN2, IL36G, and IL8 but a decrease in FLG and LOR, thereby confirming the role of activated TH17\xa0cells.'] |
['ATP-binding cassette, subfamily G, member 2 (ABCG2) is a new member of the superfamily of ATP-binding cassette transporter proteins and known to be not only a member of the membrane transporters implicated in multidrug resistance, but also a molecular determinant of the side population phenotype, characteristics of which are reminiscent of stem cells. The aim of the current study was to clarify the significance of ABCG2 expression in esophageal squamous cell carcinoma (ESCC).', 'We immunohistochemically investigated paraffin sections of 100 ESCC tumors and assessed the expression level of ABCG2 mRNA in 33 specimens by quantitative RT-PCR.', "In the immunohistochemical study, ABCG2 expression was detectable in 61% of patients and the proportion of ABCG2-positive cells was variable (0-100%). Interestingly, the presence of ABCG2-positive cells in the tumor, regardless of their amount, was associated with poorer survival (p = 0.0088). Moreover, it was revealed to be an independent prognostic factor along with the extent of the primary tumor and positive lymph node metastasis in multivariate analysis using Cox's regression model. In the quantitative RT-PCR study, higher tumor ABCG2 mRNA expression was associated with poorer survival (p = 0.017)."] |
['To examine whether iNOS contributes to endothelial dysfunction in aged rats.', 'Male Sprague Dawley rats were divided into three groups: young rats, aged rats treated with vehicle and aged rats treated with N-[3-(Aminomethyl) benzyl] acetamidine (1400W, 1 mg/kg, ip). Vasorelaxation was measured in isolated thoracic aorta. iNOS expression of thoracic aortic arteries was detected using immunohistochemistry and Western blot. Nitrotyrosine (a marker for peroxynitrite formation) content and expression in thoracic aortic tissue were determined using enzyme linked immunosorbent assay and immunohistochemistry.', 'Maximal relaxation induced by acetylcholine (10⁻⁹ to 10⁻⁵ mol/L) in the aged rats treated with vehicle was significantly decreased (70%±15%, P<0.01), as compared with the young rats (95%±8%). However, the maximal relaxation induced by acidified NaNO2 (an endothelium-independent vasodilator) had no significant difference between the two groups. Moreover, iNOS and nitrotyrosine expression increased in the vessels of the aged rats. In the aged rats treated with 1400W (a highly selective iNOS inhibitor) nitrotyrosine expression was reduced and acetylcholine-induced vasorelaxation was markedly improved (maximal relaxation was increased to 87%±8%, P<0.05), but the acidified NaNO₂-induced vasorelaxation had no significant change.'] |
['Severe dengue with severe plasma leakage (SD-SPL) is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.', 'Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS). To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ) technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.', 'Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05), with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.'] |
['The consequences of delirium in the emergency department (ED) remain unclear. This study sought to determine if delirium in the ED was an independent predictor of prolonged hospital length of stay (LOS).', 'This prospective cohort study was conducted at a tertiary care, academic ED from May 2007 to August 2008. The study included English-speaking patients aged 65 and older who were in the ED for less than 12 hours at enrollment. Patients were excluded if they refused consent, were previously enrolled, were unable to follow simple commands at baseline, were comatose, or did not have a delirium assessment performed by the research staff. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) was used to determine delirium status. Patients who were discharged directly from the ED were considered to have a hospital LOS of 0 days. To determine if delirium in the ED was independently associated with time to discharge, Cox proportional hazard regression was performed adjusted for age, comorbidity burden, severity of illness, dementia, functional impairment, nursing home residence, and surgical procedure. A sensitivity analysis, which included admitted patients only, was also performed.', 'A total of 628 patients met enrollment criteria. The median age was 75 years (interquartile range [IQR] = 69-81), 365 (58%) patients were female, 111 (18%) were nonwhite, 351 (56%) were admitted to the hospital, and 108 (17%) were delirious in the ED. Median LOS was 2 days (IQR = 0-5.5) for delirious ED patients and 1 day (IQR = 0-3) for nondelirious ED patients (p < 0.001). The hazard ratio (HR) of delirium for time to discharge was 0.71 (95% confidence interval [CI] = 0.57 to 0.89) after adjusting for confounders, and indicated that ED patients with delirium were more likely to have prolonged hospital LOS compared with those without delirium. For the sensitivity analysis, which included only hospitalized patients, the adjusted HR was 0.76 (95% CI = 0.58 to 0.99).'] |
['Plasmodium falciparum STEVOR proteins, encoded by the multicopy stevor gene family have no known biological functions. Their expression and unique locations in different parasite life cycle stages evoke multiple functionalities. Their abundance and hypervariability support a role in antigenic variation.', 'Immunoblotting of total parasite proteins with an anti-STEVOR antibody was used to identify variant antigens of this gene family and to follow changes in STEVOR expression in parasite populations panned on CSA or CD36 receptors. Immunofluorescence assays and immunoelectron microscopy were performed to study the subcellular localization of STEVOR proteins in different parasite stages. The capacity of the antibody to inhibit merozoite invasion of erythrocytes was assessed to determine whether STEVOR variants were involved in the invasion process.', 'Antigenic variation of STEVORs at the protein level was observed in blood stage parasites. STEVOR variants were found to be present on the merozoite surface and in rhoptries. An insight into a participation in erythrocyte invasion was gained through an immunofluorescence analysis of a sequence of thin slides representing progressive steps in erythrocyte invasion. An interesting feature of the staining pattern was what appeared to be the release of STEVORs around the invading merozoites. Because the anti-STEVOR antibody did not inhibit invasion, the role of STEVORs in this process remains unknown.'] |
['The importance of the distribution of safe, effective and cost-effective pharmaceutical products in resource-constrained countries is the subject of increasing attention. FHI 360 has developed a program aimed at evaluating the quality of a contraceptive implant manufactured in China, while the product is being registered in an increasing number of countries and distributed by international procurement agencies. The program consists of (1) independent product testing; (2) ongoing evaluation of the manufacturing facility through audits and inspections; and (3) post-marketing surveillance.', 'This article focuses on the laboratory testing of the product. The various test methods were chosen from the following test method compendia, the United States Pharmacopeia (USP), British Pharmacopeia (BP), International Organization for Standardization (ISO), the American Society for Testing and Materials (ASTM), or lot release tests mandated by Chinese regulatory requirements. Each manufactured lot is independently tested prior to its distribution to countries supported by this program. In addition, a more detailed annual testing program includes evaluation of the active ingredient (levonorgestrel), the final product and the packaging material.', 'Over the first 4 years of this 5-year project, all tested lots met the established quality criteria.'] |
['Digital nerve blocks are commonly used as effective techniques of anaesthesia to allow a variety of surgical procedures performed on digits. This study was conducted to compare the efficacy of volar subcutaneous single injection block and the traditional dorsal two injections digital block.', 'This randomized controlled trial was conducted at Plastic and Reconstructive Surgery Department, Hayatabad Medical Complex Peshawar from December. 2009-10. A total of 126 patients with pathology distal to the first palmer digital crease divided into two equal groups. Group A received volar subcutaneous digital block while group B dorsal two injections block. Efficacy of digital block was measured in terms of time of onset of anaesthesia, which was the total time duration after administering local anaesthetic to loss of pinprick sensation and total duration of anaesthesia, which was defined as the time period from onset of block (loss of pinprick sensation) till the appearance of pain which required additional local anaesthetic or postoperative analgesia.', 'A total of 126 patients were studied, 63 in each group. Of the total patients, 102 (81%) were male and 24 (19%) female with a mean age of 27 ± 4.2 years (range 17-60 years). The mean time of onset of anaesthesia from injection till the loss of pin prick sensation was 3.32 ± 0.42 minutes for volar single injection group and 4.53 minutes ± 0.57 minutes for dorsal two injections group (p = 0.049). Similarly the mean total duration of anaesthesia for the volar subcutaneous group was 271.9 ± 29.34 minutes while for the dorsal two injections group, it was 229.52 ± 28.82 minutes (p = 0.415).'] |
['To compare four different blood pressure (BP) measurements-systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)-in predicting future metabolic syndrome (MetS) among the normotensive elderly population, and to estimate the optimal cutoff value of the best single measurement for clinical practice.', 'A total of 2782 non-medicated participants aged ≥ 60 years were enrolled in a standard health examination program in Taiwan from January 2004 to December 2013. Two thirds of the participants were randomly designated as the training group (n=1855) and the other one third as the validation group (n=927). The mean follow-up time was 3.60 years for both the training and validation groups. MAP and PP were calculated from SBP and DBP.', "SBP, DBP, and MAP were associated with future MetS, whereas PP was not. MAP had the largest hazard ratio in Cox regression (men 1.342 [95% CI 1.158-1.555] and women 1.348 [95% CI 1.185-1.534] in the training group; men 1.640 [95% CI 1.317-2.041] and women 1.485 [95% CI 1.230-1.794] in the validation group) and the largest area under the receiver operating characteristic curve (men 0.598 ± 0.021 and women 0.602 ± 0.021 in the training group). Multivariable Cox regression further indicated that a higher MAP level was independently associated with the future occurrence of MetS. Participants with MAP above the cutoff value (84.0mm Hg for men, 83.3mm Hg for women) had a higher cumulative incidence of MetS than did their counterparts after four years' follow-up in both the training and validation groups. The results derived from the training data could be replicated in the validation data, indicating that the results were generalizable across distinct samples."] |
['Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact.', 'Bone marrow and peripheral blood were collected before NACT (BM1: n = 231/PB1: n = 219), at surgery (BM2: n = 69/PB2: n = 71), and after 12 months from start of NACT (BM3: n = 162/PB3: n = 141). Patients were included from 1997 to 2003 and followed until 2009 (or ten years follow-up). DTC- and CTC-status were determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. The prognostic significance of DTCs/CTCs was assessed by univariate and multivariate Cox-regression analyses.', 'Before NACT, DTCs and CTCs were detected in 21.2% and 4.9% of the patients, respectively. At surgery, 15.9% and 1.4% had DTC- and CTC-presence, compared to 26.5% and 4.3% at 12 months from start of NACT. Of patients for whom DTC results both before NACT and at 12 months were available, concordant results were observed in 68%, and 14 out of 65 had positive DTC-status at both time points. Presence of ≥ 1 DTC 12 months from start of NACT, but not at other time points, predicted reduced disease-free survival (DFS; HR 2.3, p = 0.003), breast cancer-specific survival (BCSS; HR 3.0, p < 0.001) and overall survival (OS; HR 2.8, p < 0.001). Before NACT, presence of ≥ 3 DTCs was also associated with unfavorable outcome, and reduced BCSS was observed for CTC-positive patients (HR 2.2, p = 0.046). In multivariate analysis, DTC status (</≥ 1 DTC) at 12 months after start of NACT remained as a prognostic factor for both DFS (HR 2.2, p = 0.005), BCSS (HR 2.6, p = 0.002) and OS (HR 2.6, p = 0.002). The survival for patients with change in DTC-status was determined by the DTC-status at 12 months.'] |
['In vitro generation and expansion of leukemia-reactive T cells may improve the efficacy and specificity of cellular immunotherapy against hematologic malignancies in the context of allogeneic stem cell transplantation. Since the expression of minor histocompatibility antigen HA-1(H) is limited to hematopoietic cells, ex vivo generated HA-1(H)-specific CD8+ cytotoxic T lymphocytes (CTLs) can be used for adoptive immunotherapy.', 'Numerous studies have shown that primary CTL induction from naïve precursors requires professional antigen-presenting cells. Here, the feasibility of ex vivo induction of HA-1(H)-specific CD8+ CTLs is demonstrated from unfractionated peripheral blood mononuclear cells (PBMNCs) from healthy blood donors when CD4+ T-cell help is provided during primary stimulation. As a stimulus for the induction of T-cell help, tetanus toxoid (TT) was used.', 'After the second restimulation cycle, approximately 1 percent of CD8+ T cells stained positively with the HLA-A*0201/HA-1(H) pentamer. Positive T cells were further expanded more than 1000-fold by antigen-independent stimulation with anti-CD3/CD28 monoclonal antibodies. HA-1(H)-induced T cells showed the classical phenotype for CD8+ memory effector cells: the phenotype changed from a mixed CD45RA/RO phenotype to an activated phenotype characterized by high expression of CD45RO and no expression of CCR7. The generated T cells revealed a very potent CTL response, even at low E:T ratios.'] |
['Percutaneous transluminal coronary angioplasty (PTCA) reduces in-hospital mortality and improves long-term outcome in patients with acute myocardial infarction (MI) complicated by cardiogenic shock. However, no study has evaluated the effects of different reperfusion therapies on left ventricular (LV) dimension and cardiac function in long-term survivors of MI with cardiogenic shock.', 'We investigated the effects of PTCA on the development of LV dilation in patients who survived MI complicated by cardiogenic shock.', 'We studied 34 patients with a first MI and cardiogenic shock in whom two-dimensional echocardiography was performed immediately after admission and 1 month after infarction. Group A consisted of 17 patients who underwent emergent PTCA during the acute phase of MI, and Group B consisted of 17 patients who did not undergo PTCA. We also studied 119 patients with a first uncomplicated acute anterior MI, including 53 who underwent PTCA (Group C) and 66 who did not (Group D). The length and wall thickness of the infarcted and noninfarcted endocardial segments were determined immediately after MI and 1 month later, and LV ejection fraction (LVEF) was measured during the chronic phase.', 'The lengths of the infarcted and noninfarcted endocardial segments were significantly greater in Group B than in the other three groups (p < 0.05). The LVEF was significantly lower in Group B than in the other three groups (p < 0.05).'] |
['Generation of cell-fate diversity in Metazoan depends in part on asymmetric cell divisions in which cell-fate determinants are asymmetrically distributed in the mother cell and unequally partitioned between daughter cells. The polarization of the mother cell is a prerequisite to the unequal segregation of cell-fate determinants. In the Drosophila bristle lineage, two distinct mechanisms are known to define the axis of polarity of the pI and pIIb cells. Frizzled (Fz) signaling regulates the planar orientation of the pI division, while Inscuteable (Insc) directs the apical-basal polarity of the pIIb cell. The orientation of the asymmetric division of the pIIa cell is identical to the one of its mother cell, the pI cell, but, in contrast, is regulated by an unknown Insc- and Fz-independent mechanism.', 'DE-Cadherin-Catenin complexes are shown to localize at the cell contact between the two cells born from the asymmetric division of the pI cell. The mitotic spindle of the dividing pIIa cell rotates to line up with asymmetrically localized DE-Cadherin-Catenin complexes. While a complete loss of DE-Cadherin function disrupts the apical-basal polarity of the epithelium, both a partial loss of DE-Cadherin function and expression of a dominant-negative form of DE-Cadherin affect the orientation of the pIIa division. Furthermore, expression of dominant-negative DE-Cadherin also affects the position of Partner of Inscuteable (Pins) and Bazooka, two asymmetrically localized proteins known to regulate cell polarity. These results show that asymmetrically distributed Cad regulates the orientation of asymmetric cell division.'] |
['Chronic hyperglycaemia increases dipeptidyl peptidase IV (DPP-IV) activity in endothelial cells in vitro. The present study was designed to assess the effect of high glucose on circulating DPP-IV activity in patients with type 1 and type 2 diabetes.', 'Plasma DPP-IV activity was measured in 29 patients with type 1 diabetes and 29 age-, sex- and BMI-matched control subjects. We also assessed DPP-IV activity in 31 type 2 diabetic patients with HbA1c > 8.5% and in plasma from matched groups of 31 newly diagnosed diabetic subjects with HbA1c < 7.5%, 31 subjects with IGT and 62 subjects with NGT. In a further sample of 66 type 2 diabetic patients, a longitudinal study was also performed to evaluate variations in DPP-IV activity and HbA1c over 3 months.', 'DPP-IV activity in type 1 diabetic patients was not significantly different from that in control subjects; however, a significant correlation between DPP-IV and HbA1c was observed in diabetic subjects (r = 0.47; p < 0.01). Type 2 diabetic patients with HbA1c > 8.5% showed significantly (p < 0.05) higher DPP-IV activity (mean+/-SD 27.7+/-7.1 U/l) than newly diagnosed diabetic patients and subjects with IGT (22.1+/-6.0 and 18.8+/-8.8 U/l, respectively). Variations in DPP-IV activity over 3 months in type 2 diabetic patients showed a significant positive correlation with variations in HbA1c (r = 0.26; p < 0.05).'] |
['Hypertension is associated with an increase in platelet activation and endothelial dysfunction and leads to a tendency to cardiovascular events (CVEs). Signal peptide-CUB-EGF domain-containing protein 1 (SCUBE1) is a novel platelet activation marker. There are currently no studies showing the level of SCUBE1 in hypertensive patients. The purpose of this study was to determine the level of SCUBE1 in this patient group and to investigate the parameters affecting that level.', 'Forty-five newly diagnosed, untreated, stage 1 hypertensive patients and 21 healthy individuals were included. Blood specimens were collected to determine SCUBE1, soluble CD40 ligand, prothrombin time, partial thromboplastin time, fibrinogen, D dimer, hemogram, lipid parameters, blood urea nitrogen, creatinine, and uric acid levels. The relation between SCUBE1 level and demographic data and biochemical parameters was then investigated.', 'SCUBE1 and sCD40L levels obtained from plasma specimens from the hypertensive group were significantly higher than those of the control group (P < 0.001; P < 0.05, respectively). Hypertensive group blood pressure (BP) values and uric acid, low-density lipoprotein, total cholesterol, and triglyceride levels were also statistically higher than those of the control group. Parameters affecting SCUBE1 levels were systolic and diastolic BP, sCD40L, lipid parameters, and uric acid levels.'] |
['Predictors of future stroke events gain importance in vascular medicine. Herein, we investigated the value of the ankle-brachial index (ABI), a simple non-invasive marker of atherosclerosis, as stroke predictor in addition to established risk factors that are part of the Framingham risk score (FRS).', '4299 subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.3% men) without previous stroke, coronary heart disease or myocardial infarcts were followed up for ischemic and hemorrhagic stroke events over 109.0±23.3 months. Cox proportional hazard regressions were used to evaluate ABI as stroke predictor in addition to established vascular risk factors (age, sex, systolic blood pressure, LDL, HDL, diabetes, smoking).', '104 incident strokes (93 ischemic) occurred (incidence rate: 2.69/1000 person-years). Subjects suffering stroke had significantly lower ABI values at baseline than the remaining subjects (1.03±0.22 vs. 1.13±0.14, p<0.001). In a multivariable Cox regression, ABI predicted stroke in addition to classical risk factors (hazard ratio=0.77 per 0.1, 95% confidence interval=0.69-0.86). ABI predicted stroke events in subjects above and below 65 years, both in men and women. ABI specifically influenced stroke risk in subjects belonging to the highest (>13%) and intermediate (8-13%) FRS tercile. In these subjects, stroke incidence was 28.13 and 8.13/1000 person-years, respectively, for ABI<0.9, compared with 3.97 and 2.07/1000 person-years for 0.9≤ABI≤1.3.'] |
['Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling.', 'Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography-Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8+/-0.6 mm in MI vs. 3.6+/-0.3 mm in sham; P<0.0001), as was atrial fibrosis (26.7+/-3.8% in MI vs. 10.5+/-2.2% in sham; P<0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration.'] |
['Periodontitis is a bacterial infection of the periodontal tissues. The Gram-negative anaerobic bacterium Porphyromonas gingivalis is considered a major causative agent. One of the virulence factors of P. gingivalis is capsular polysaccharide (CPS). Non-encapsulated strains have been shown to be less virulent in mouse models than encapsulated strains.', 'To examine the role of the CPS in host-pathogen interactions we constructed an insertional isogenic P. gingivalis knockout in the epimerase-coding gene epsC that is located at the end of the CPS biosynthesis locus. This mutant was subsequently shown to be non-encapsulated. K1 capsule biosynthesis could be restored by in trans expression of an intact epsC gene. We used the epsC mutant, the W83 wild type strain and the complemented mutant to challenge human gingival fibroblasts to examine the immune response by quantification of IL-1beta, IL-6 and IL-8 transcription levels. For each of the cytokines significantly higher expression levels were found when fibroblasts were challenged with the epsC mutant compared to those challenged with the W83 wild type, ranging from two times higher for IL-1beta to five times higher for IL-8.'] |
['The L1 cell adhesion molecule (L1CAM) is potentially involved in epithelial-mesenchymal transition (EMT). EMT marker expression is of prognostic significance in non-small cell lung cancer (NSCLC). The relevance of L1CAM for NSCLC is unclear. We investigated the protein expression of L1CAM in a cohort of NSCLC patients. L1CAM protein expression was correlated with clinico-pathological parameters including survival and markers of epithelial-mesenchymal transition.', 'L1CAM protein expression was found in 25% of squamous cell carcinomas and 24% of adenocarcinomas and correlated with blood vessel invasion and metastasis (p < 0.05). L1CAM was an independent predictor of survival in a multivariate analysis including pT, pN, and pM category, and tumor differentiation grade. L1CAM expression positively correlated with vimentin, beta-catenin, and slug, but inversely with E-cadherin (all p-values < 0.05). E-cadherin expression was higher in the tumor center than in the tumor periphery, whereas L1CAM and vimentin were expressed at the tumor-stroma interface. In L1CAM-negative A549 cells the L1CAM expression was upregulated and matrigel invasion was increased after stimulation with TGF-beta1. In L1CAM-positive SK-LU-1 and SK-LC-LL cells matrigel invasion was decreased after L1CAM siRNA knockdown.'] |
['Recent evidence suggests that succinate, long known as an intermediate in the citric acid cycle, may also have a role as a signaling molecule through GPR91 and that activation of this receptor results in blood pressure (BP) elevation via the renin-angiotensin system. We sought to test the hypothesis that GPR91 contributes to BP elevation in hypertension. In addition we investigated whether elevated succinate in diabetes could contribute to the increased rate of gluconeogenesis in that condition.', 'Circulating succinate concentration was measured using liquid chromatography tandem mass spectrometry in rodent models of hypertension and metabolic disease as well as in human hypertensives and type 2 diabetics in comparison to control subjects.', 'Elevated succinate was detected in spontaneously hypertensive rats (SHR), ob/ob mice, db/db mice, and fa/fa rats in comparison to their non-diseased controls. The changes in concentration are consistent with activation of GPR91. In contrast, neither human hypertensives nor diabetic patients had elevated succinate in comparison to controls.'] |
['Cystic fibrosis (CF) is an autosomal recessive disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The purpose of this study was to develop a molecular method to characterise both paternal and maternal CFTR alleles in DNA from circulating fetal cells (CFCs) isolated by ISET (isolation by size of epithelial tumour/trophoblastic cells).', 'The molecular protocol was defined by developing the F508del mutation analysis and addressing it both to single trophoblastic cells, isolated by ISET and identified by short tandem repeats (STR) genotyping, and to pooled trophoblastic genomes, thus avoiding the risk of allele drop out (ADO). This protocol was validated in 100 leucocytes from F508del carriers and subsequently blindly applied to the blood (5 mL) of 12 pregnant women, at 11 to 13 weeks of gestation, whose offspring had a 1/4 risk of CF. Ten couples were carriers of F508del mutation, while two were carriers of unknown CFTR mutations.', 'Results showed that one fetus was affected, seven were heterozygous carriers of a CFTR mutation, and four were healthy homozygotes. These findings were consistent with those obtained by chorionic villus sampling (CVS).'] |
['Prenatal alcohol exposure can disrupt central nervous system development, manifesting as behavioral deficits that include motor, emotional, and cognitive dysfunction. Both clinical and animal studies have reported binge drinking during development to be highly correlated with an increased risk of fetal alcohol spectrum disorders (FASD). We hypothesized that binge drinking may be especially damaging because it is associated with episodes of alcohol withdrawal. Specifically, we have been investigating the possibility that NMDA receptor-mediated excitotoxicity occurs during alcohol withdrawal and contributes to developmental alcohol-related neuropathology. Consistent with this hypothesis, administration of the NMDA receptor antagonists MK-801 or eliprodil during withdrawal attenuates behavioral alterations associated with early alcohol exposure. In this study, we investigated the effects of memantine, a clinically used NMDA receptor antagonist, on minimizing ethanol-induced overactivity and spatial learning deficits.', "Sprague-Dawley pups were exposed to 6.0\xa0g/kg ethanol via intubation on postnatal day (PD) 6, a period of brain development that models late gestation in humans. Controls were intubated with a calorically matched maltose solution. During withdrawal, 24 and 36\xa0hours after ethanol exposure, subjects were injected with a total of either 0, 20, or 30\xa0mg/kg memantine. The subjects' locomotor levels were recorded in open field activity monitors on PDs 18 to 21 and on a serial spatial discrimination reversal learning task on PDs 40 to 43.", 'Alcohol exposure induced overactivity and impaired performance in spatial learning. Memantine administration significantly attenuated the ethanol-associated behavioral alterations in a dose-dependent manner. Thus, memantine may be neuroprotective when administered during ethanol withdrawal.'] |
['To compare the efficacy of adding formoterol or salbutamol to regular ipratropium bromide treatment in COPD patients whose conditions were suboptimally controlled with ipratropium bromide alone.', 'A randomized, double-blind, double-dummy, two-period, crossover clinical trial.', 'Twenty-four clinics and university medical centers in nine countries.', 'One hundred seventy-two patients with baseline FEV(1) < or = 65% predicted, with FEV(1) reversibility to salbutamol not exceeding the normal variability of the measurement, and symptomatic despite regular treatment with ipratropium bromide.', 'Each patient received two treatments in random order: either inhaled formoterol dry powder, 12 microg bid, in addition to ipratropium bromide, 40 microg qid for 3 weeks, followed by salbutamol, 200 microg qid, in addition to ipratropium, 40 microg qid for 3 weeks, or vice versa.', 'Efficacy end points included morning premedication peak expiratory flow (PEF) during the last week of treatment (primary end point), the area under the curve (AUC) for FEV(1) measured for 6 h after morning dose on the last day of treatment, and symptom scores (from daily diary recordings). Morning PEF and the AUC for FEV(1) were significantly better for formoterol/ipratropium than for salbutamol/ipratropium (p = 0.0003 and p < 0.0001, respectively). The formoterol/ipratropium combination also induced a greater improvement in mean total symptom scores (p = 0.0042). The safety profile of the two treatments was comparable.'] |
['Temporomandibular joint malformation is a complex deformity in Treacher-Collins syndrome (TCS); however, it is not well characterized. This study aimed to better clarify this pathology by volumetrically assessing the mandibular condyle in patients with TCS compared with normal controls and the relative contribution of the condyle to hemimandibular volume.', 'A retrospective, cross-sectional analysis of pediatric patients with TCS and unaffected controls was performed. The study sample was comprised of Treacher Collins patients. The predictor variable in this study was disease status (TCS diagnosis vs control), and the outcome variable was condylar volume. Demographic information was collected, and 3-dimensional computed tomographic data were analyzed by computerized segmentation (Materialise). Volumes were obtained for TCS condyles and compared with age-matched controls using the Student t test.', 'Three-dimensional computed tomographic scans were identified in 10 patients with TCS (20 sides) and 14 control subjects (28 sides). The TCS group included 4 female and 6 male patients (age, 0.3 to 213 mo; average age, 66.5 mo). The control cohort included 7 female and 7 male subjects (average age, 68.8 mo). Evaluation of the mandibular condyle showed that patients with TCS had a significantly smaller condylar volume than control patients (TCS, 178.28 ± 182.74 mm(3); control, 863.55 ± 367.20 mm(3); P < .001). Additional intragroup analysis showed no significant differences between the left and right condylar volumes in the TCS group (P = .267). In addition, the condyle for patients with TCS represented a smaller proportion of hemimandibular volume compared with controls (1.37% vs 4.19%, respectively; P < .001).'] |
['Thyroid nodules are selected for biopsy on the basis of clinical and ultrasound (US) findings. Ultrasonography detects nodules at risk of malignancy, but its diagnostic accuracy does not rule out with certainty the possibility of cancer in lesions without suspicious findings.', 'The objective of the study was to evaluate the diagnostic accuracy of real-time elastography (RTE) in thyroid nodules and to assess the improvement provided by combination of RTE, B-mode US, and color flow Doppler (CFD).', 'This was a prospective multicenter study.', 'A consecutive series of 498 thyroid nodules was blindly evaluated by US, CFD, and RTE before biopsy or surgery. Nodules were classified at RTE by four-class color scale. Patients with benign cytology underwent follow-up over 12 months, whereas patients with indeterminate, suspicious, or malignant cytology were surgically treated.', 'At follow-up, 126 nodules were malignant and 372 benign. RTE classes III-IV showed 81% sensitivity and 62% specificity. The presence of at least one US risk factor (hypoechogenicity, microcalcifications, irregular margins, intranodular vascularization, and taller than wide shape) had 85% sensitivity and 91% negative predictive value. When RTE was combined with US, the presence of at least one of the six parameters had 97% sensitivity and 97% negative predictive value, with an odds ratio of 15.8 (95% confidence interval 5.7-43.8).'] |
['The underlying biological mechanism in the formation of adverse local tissue reaction in taper corrosion of total hip arthroplasty (THA) remains unknown. This study evaluated whether there was a dose-dependent relationship between metal ion levels, intraoperative tissue damage and ALVAL (aseptic lymphocyte-dominated vasculitis-associated lesion) scores in dual taper THA patients who underwent revisions for taper corrosion.', 'We performed a retrospective review of 31 dual taper THA patients who underwent revision surgery from May 2013 to October 2013. Preoperative serum metal ion levels, intraoperative tissue damage grading, and ALVAL scores were reviewed. Multivariate analysis was performed to determine if an association existed between metal ion levels, intraoperative tissue damage, and ALVAL scores.', 'Findings consistent with adverse local tissue reaction were found in all cases. We noted 10 patients with low, 8 with moderate, and 13 with high ALVAL scores, respectively. For intraoperative tissue damage, we recorded 2 (grade 1), 22 (grade 2) and 7 (grade 3) cases. Preoperatively, there was preferential elevation of serum cobalt (3.8 ng/mL, 2.3-17.0) compared to serum chromium (1.0 ng/mL, 0.2-5.8). There was no correlation between preoperative metal ion levels and intraoperative tissue damage (R\xa0=\xa0-0.06, P\xa0= .74) or ALVAL scores (R\xa0=\xa0-0.04, P\xa0= .481). There was also no correlation between intraoperative tissue damage and ALVAL score (R\xa0=\xa0-0.06, P\xa0= .73).'] |
['In vivo application of the K(ATP)-channel blocker glibenclamide can reverse endotoxin-induced hypotension, vascular hyporeactivity and shock in experimental animals. The hypothesis of the present study is, that the drug effects might not only be based on direct inhibition of K(ATP)-channels of vascular smooth muscle cells, but might also reflect reduction of shock-induced excess proinflammatory cytokines and procoagulatory molecules produced in the blood monocytes.', 'Human whole blood (normoxaemic or hypoxaemic) supplemented ex vivo with 100 ng/ml LPS was used to assess glibenclamide (3-100 μM) effects on IL-1 beta, IL-6, TNF-alpha, tissue factor, and plasminogen-activator-inhibitor-2 (PAI-2). Co-incubations with monocytes and erythrocytes and cytosolic calcium measurements were performed to reveal their purinergic intercellular interaction.', 'In heparinized blood, glibenclamide reduced LPS-induced release of IL-1 beta and TNF-alpha, tissue factor and PAI-2 mRNA in a concentration-dependent manner. When samples were subjected to strong hypoxemia using 95% N(2)/5% CO(2), these parameters became even more sensitive to the drug. No drug effect was observable in citrated blood or in isolated monocytes. IL-1 beta mRNA inhibition by glibenclamide appeared to be dependent on P2X7-receptor activation of monocytes by ATP-releasing erythrocytes during hypoxia. Cytosolic calcium values as well as the duration of calcium transients elicited by P2X7-receptor stimulation in isolated monocytes were strongly increased during hypoxia, both of which could be abolished by glibenclamide.'] |
['The mouse double minute 2 (MDM2) gene represents one of the central nodes in the p53 pathway. A naturally occurring T/G single nucleotide polymorphism (SNP) in the intronic promoter of MDM2, SNP309 (rs2279744), was shown to influence MDM2 expression and p53 activity. SNP in the promoter region of MDM2 gene has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. In this study, we aim to evaluate the association of SNP309 with the risk of hepatocellular carcinoma (HCC) development among Turkish population.', 'MDM2 SNP309 polymorphism was investigated in 110 confirmed subjects with HCC and 110 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay.', 'The allele frequencies of case subjects (T, 0.48; G, 0.52) were significantly different from those of control subjects (T, 0.65; G, 0.35) (p=0.003). The proportion of GG genotype of the SNP309 in patients with HCC (26%) was significantly higher than that in patients without HCC (14%). We observed that compared with the TT genotype, the genotypes containing G allele [TG (OR, 2.19; 95% CI, 1.18-4.07; p=0.013) or GG (OR, 3.63; 95% CI, 1.65-8.00; p=0.001)] were associated with significant increased susceptibility to HCC.'] |
['Transient hypoxia and subsequent reoxygenation are common phenomena in solid tumors that greatly influence the outcome of radiation therapy. This study was designed to determine how varying cycles of hypoxia/reoxygenation affect the response of cervical carcinoma cells irradiated under oxic and hypoxic conditions and whether this could be modulated by proteasome inhibition.', 'Plateau-phase SiHa cervical carcinoma cells in culture were exposed to varying numbers of 30-minute cycles of hypoxia/reoxygenation directly before irradiation under oxic or hypoxic conditions. 26S Proteasome activity was blocked by addition of MG-132. Clonogenic survival was measured by a colony-forming assay.', 'Under oxic conditions, repeated cycles of hypoxia/reoxygenation decreased the clonogenic survival of SiHa cells. This effect was even more pronounced after the inhibition of 26S proteasome complex. In contrast, under hypoxic conditions, SiHa cells were radioresistant, as expected, but this was increased by proteasome inhibition.'] |
["In normal patients the rim had a characteristic configuration with the rim width being broadest in the inferior disc region, followed by the superior, the nasal, and the temporal sector. The aim of this study was to assess whether the rim shape as measured by the Heidelberg Retina Tomograph 3 (HRT3) followed the ISN'T rule or any other specific distribution pattern.", "This is a prospectively planned cross-sectional study. Two hundred and twenty-six healthy eyes were recruited into this study. All the patients who were included had normal ocular examination, an intraocular pressure less than 21 mm Hg and a normal visual field by the Humphrey Field Analyzer (program 24-2, Swedish Interactive Threshold Analysis standard). For each patient, the optic nerve head was morphometrically evaluated by using the HRT3. All data were analyzed by the analysis of variance test and Tukey's Multiple Comparison Test.", 'When the rim area and rim volume were considered, a statistically significant difference (P<0.001) was found between the temporal rim area and superior, nasal, and inferior rim area. No significant difference was found among the superior, nasal, and inferior rim area. A similar result was found for the cup area. The temporal cup shape measure was significantly (P<0.001) different from the other disc sectors.'] |
['One of the cancer hallmarks is mitochondrial dysfunction associated with oxidative stress. Among the first line of defense against oxidative stress is the dismutation of superoxide radicals, which in the mitochondria is carried out by manganese superoxide dismutase (MnSOD). Accordingly, carcinogenesis would be associated with a dysregulation in MnSOD expression. However, the association studies available so far are conflicting, and no direct proof concerning the role of MnSOD as a tumor promoter or suppressor has been provided. Therefore, we investigated the role of MnSOD in carcinogenesis by studying the effect of MnSOD deficiency in cells and in the livers of mice.', 'We found that loss of MnSOD in hepatoma cells contributed to their conversion toward a more malignant phenotype, affecting all cellular properties generally associated with metabolic transformation and tumorigenesis. In vivo, hepatocyte-specific MnSOD-deficient mice showed changed organ architecture, increased expression of tumor markers, and a faster response to carcinogenesis. Moreover, deficiency of MnSOD in both the in vitro and in vivo model reduced β-catenin and hypoxia-inducible factor-1α levels.', 'The present study shows for the first time the important correlation between MnSOD presence and the regulation of two major pathways involved in carcinogenesis, the Wnt/β-catenin and hypoxia signaling pathway.'] |
['To examine the effectiveness of preemptive analgesia in gynecologic laparoscopy patients.', 'A double-blinded, randomized trial was performed from June 2000 to June 2001. Preoperatively, patients were randomly assigned to 0.25% bupivicaine or normal saline control. Following anesthetic induction, the study drug or a placebo was injected prior to the proposed incisions.', 'Of the 164 patients enrolled, 85 were randomized to the study group and 79 to the control. Age, surgery indication, and estimated blood loss did not vary significantly between groups. Overall mean pain score (+/-standard error of the mean) for study and control groups did not differ at 4 hours (3.2+/-0.3 vs 3.2+/-0.3) or at 24 hours (4.2+/-0.3 vs 4.2+/-0.3). Incisional pain scores also did not differ at 4 hours (3.0+/-0.3 vs 2.7+/-0.3) or at 24 hours (3.6+/-0.3 vs 3.6+/-0.3). Both groups were similar in activity limitation at 24 hours and oral narcotic consumption within 24 hours postoperatively. After stratifying surgery type for level of complexity, no difference was noted between groups. Multiple logistic regression analysis also noted no difference in outcomes.'] |
['To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human hepatic cancer cells.', "The hepatoma cell lines SK-Hep-1 and MHCC97L were used in this study. The cells were cultured in RPIM-1640 medium supplemented with 10% fetal bovine serum at 37\u2005°C in a humidified 5% CO2 incubator. DHM was dissolved in dimethyl sulfoxide and diluted to various concentrations in medium before applying to cells. MTT assays were performed to measure the viability of the cells after DHM treatment. Wound healing and Boyden transwell assays were used to assess cancer cell motility. The invasive capacity of cancer cells was measured using Matrigel-coated transwell chambers. Matrix metalloproteinase (MMP)-2/9 activity was examined by fluorescence analysis. Western blot was carried out to analyze the expression of MMP-2, MMP-9, p-38, JNK, ERK1/2 and PKC-δ proteins. All data were analyzed by Student's t tests in GraphPad prism 5.0 software and are presented as mean ± SD.", 'DHM was found to strongly inhibit the migration of the hepatoma cell lines SK-Hep-1 (without DHM, 24 h: 120 ± 8 μmol/L vs 100 μmol/L DHM, 24 h: 65 ± 10 μmol/L, P < 0.001) and MHCC97L (without DHM, 24 h: 126 ± 7 μmol/L vs 100 μmol/L DHM, 24 h: 74 ± 6 μmol/L, P < 0.001). The invasive capacity of the cells was reduced by DHM treatment (SK-Hep-1 cells without DHM, 24 h: 67 ± 4 μmol/L vs 100 μmol/L DHM, 24 h: 9 ± 3 μmol/L, P < 0.001; MHCC97L cells without DHM, 24 h: 117 ± 8 μmol/L vs 100 μmol/L DHM, 24 h: 45 ± 2 μmol/L, P < 0.001). MMP2/9 activity was also inhibited by DHM exposure (SK-Hep-1 cells without DHM, 24 h: 600 ± 26 μmol/L vs 100 μmol/L DHM, 24 h: 100 ± 6 μmol/L, P < 0.001; MHCC97L cells without DHM, 24 h: 504 ± 32 μmol/L vs 100 μmol/L DHM 24 h: 156 ± 10 μmol/L, P < 0.001). Western blot analysis showed that DHM decreased the expression level of MMP-9 but had little effect on MMP-2. Further investigation indicated that DHM markedly reduced the phosphorylation levels of p38, ERK1/2 and JNK in a concentration-dependent manner but had no impact on the total protein levels. In addition, PKC-δ protein, a key protein in the regulation of MMP family protein expression, was up-regulated with DHM treatment.'] |
["The 2-deoxystreptamine-containing aminoglycoside antibiotics (AGAs) constitute the largest subgroup of the aminoglycosides. Neomycin (NEO) and lividomycin (LIV) are both representatives of the pseudo-tetrasaccharide group among the NEO-type AGAs. While NEO contains a 6'-NH(2) group, the 6'-position remains unmodified in LIV. The aim of the study was to characterize the substrate specificities of the enzymes involved in the C-6'- and C-6‴-modification in order to explain the different amination patterns.", "We overproduced and purified the enzymes NeoQ (bifunctional 6'- and 6‴-oxidoreductase) and NeoB (bifunctional 6'- and-6‴-aminotransferase), which had been analysed before (Huang et al. 2007), and compared the enzymatic properties with the corresponding enzymes LivQ (postulated 6‴-oxidoreductase, 72% identity to NeoQ) and LivB (postulated 6‴-aminotransferase, 71% identity to NeoB) from the LIV pathway. By applying a newly established photometric assay, we proved that LivQ oxidized only pseudotetrasaccharidic substrates at the 6‴-position. In contrast, NeoQ accepted also the pseudodisaccharidic paromamine as a substrate and oxidized the 6'- and 6‴-positions on two different precursors of NEO. The aminotransferases LivB and NeoB both transfer NH(2) groups to the 6'-position in the precursor 6'-oxo-paromamine and to the 6‴-position of 6‴-oxo-neomycin C."] |
['Intra-ventricular hemorrhage (IVH) is a frequent cause of shunt-dependent hydrocephalus. The management of IVH in preterm babies remains a challenge both for neonatologists and pediatric neurosurgeons, compounded by the lack of low-risk, validated therapy techniques.', 'The aim of this study was to evaluate the feasibility and safety of a novel technique involving the ultrasound-guided placement of a central catheter connected with a Rickham-Capsule in a cohort of preterm, low-birth-weight babies with post-hemorrhagic hydrocephalus (PHH).', 'Eight preterm infants with PHH in which a Rickham-Capsule was placed from 2008-2012 were included. Conventional surgical techniques were used in four preterm infants; whereas in the other four preterm babies ultrasound guided catheter placement was performed with an 8 MegaHertz (MHz) micro convex transducer from LOGIQ 9, GE Healthcare; whereby the anterior fontanel was used as an acoustic window.', 'Overall gestational age was 24-31 weeks, mean age at operation was 20.1 (7-36) days, mean birth weight 972.5±370 g, mean weight at first surgical intervention 1023.75±400.4 g. Six patients had bilateral IVH II-III°, two patients had parenchymal involvement. Using the conventional approach, incorrect catheter placement occurred in one of four patients below 1000 g, whereas none of the ultrasound guided cases needed correction.'] |
['Neurally Adjusted Ventilatory Assist (NAVA) offers synchronized proportional pressure in accordance with the electrical activity of the diaphragm (EAdi). NAVA relies on the EAdi to trigger the respiratory cycle and then adjusts the ventilatory assist to the neural drive. The technique necessitates a catheter with bipolar microelectrodes positioned near the crural diaphragm where this signal can be captured. Capturing a reliable EAdi signal is a condition sine qua non for using NAVA as a mode of ventilation. The displayed signal represents the sum of the electrical activity of the muscle action potential of the diaphragm and is expressed in microvolts.', 'A technical note illustrated by a case series in the intensive care unit (ICU) of a tertiary referral hospital with experience using NAVA.', 'Here, we report on three separate cases in which the use of an intra-aortic balloon catheter, a pacemaker and a heating device all resulted in a distortion of the EAdi signal, despite good positioning of the catheter. In a fourth case, we observed internal interference from leaking cardiac electrical activity due to the malpositioning of the EAdi catheter in a patient with atrial fibrillation.'] |
['Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast cancer cells are not fully understood. The aim of this study was to investigate short-term and long-term effects of relaxin on cancer cell motility and S100A4 expression and to determine the long-term effects of relaxin on in vivo tumour growth in an oestrogen-independent context.', 'We have established stable transfectants of highly invasive oestrogen-receptor alpha-negative MDA-MB-231 human breast cancer cells with constitutive expression of bioactive H2-relaxin (MDA/RLN2). RLN2 secretion was determined by ELISA. Relaxin receptor RXFP1 (Relaxin-family-peptide) was detected by reverse transcription (RT) PCR and its activation was assessed by induction of cyclic adenosine monophosphate (cAMP). Stable MDA/RLN2 clones and RLN2 treated MDA-MB-231 cells were subjected to motility and in vitro-invasion assays. Proliferation was assessed in bromodeoxyuridine (BrdU) and MTT assays. S100A4 expression was determined by RT-PCR and Western blot. Specific small interfering RNA was employed to down-regulate relaxin receptor and S100A4. MDA/EGFP vector control and two MDA/RLN2 clones were injected subcutaneously in nude mice to determine tumour growth and cancer cell invasiveness in vivo. Xenograft tumour tissues were assessed by histology and immunohistochemistry and frozen tissues were used for the detection of S100A4 and RLN2.', 'Short-term exposure to relaxin for 24 hours increased cell motility in a relaxin receptor-dependent manner. This increase in cell motility was mediated by S100A4. Long-term exposure to relaxin secreted from stable transfectants reduced cell motility and in vitro invasiveness. Relaxin decreased cell proliferation and down-regulated cellular S100A4 levels in MDA-MB-231 and T47D breast cancer cells. Stable MDA/RLN2 transfectants produced smaller xenograft tumours containing reduced S100A4 protein levels in vivo.'] |
['Prospective randomised controlled study.', 'Operation unit in a tertiary academic university hospital in a central European city. Period of the study was springtime and summer 2010.', 'Twenty-four anaesthesiologists with various levels of professional experience were allocated to intubate an airway manikin either with the SensaScope (group S) or with the conventional Macintosh 3 laryngoscope (group L).', "Each participant performed three consecutive intubations with normal anatomy followed by three intubations with difficult anatomy. The airway difficulty was simulated by inflation of the manikin's tongue base with 40 ml of air. The times taken to view the larynx and to insert the tracheal tube were noted. The resulting tube position and the occurrence of dental damage were recorded.", 'Those planned in the protocol.', 'In normal anatomy, the laryngeal view (group L 5.9 ± 4.2 s vs. group S 9.2 ± 3.5 s) and intubation (group L 13.4 ± 7.6 s vs. group S 23.3 ± 8.6 s) was more rapidly obtained with conventional laryngoscopy (values presented as mean ± SD). In difficult anatomy, only the SensaScope permitted successful laryngeal view (group L impossible vs. group S 9.9 ± 4.8 s) and tracheal intubation (group L impossible vs. group S 23.4 ± 8.8 s). The latter always enabled correct tracheal tube position, whereas with laryngoscopy alone either oesophageal intubation or aborted attempts resulted. In the difficult airway setting, the frequency of simulated tooth damage was also significantly higher with conventional laryngoscopy (group L 26 of 36 vs. group S 6 of 36).'] |
['The human endometrium periodically breaks down and regenerates. As platelets have been reported to contribute to the tissue remodeling process, we examined the possible involvement of platelets in endometrial regeneration.', 'The distribution of extravasating platelets throughout the menstrual cycle was immunohistochemically examined using human endometrial tissues. EM-E6/E7/hTERT cells, a human endometrial epithelial cell-derived immortalized cell line, were co-cultured with platelets, and the effects of platelets on the epithelialization response of EM-E6/E7/hTERT cells were investigated by attachment and permeability assays, immunohistochemical staining, and Western blot analysis.', 'Immunohistochemical study showed numerous extravasated platelets in the subluminar stroma during the menstrual phase. The platelets promoted the cell-to-matrigel attachment of EM-E6/E7/hTERT cells concomitantly with the phosphorylation of focal adhesion kinase. They also promoted cell-to-cell contact among EM-E6/E7/hTERT cells in parallel with E-cadherin expression.'] |
['Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population.', "MI cases (n=1650) were matched to population-based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295).", 'Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations.'] |
['In patients with heart failure (HF), serum erythropoietin (EPO) levels are elevated and associated with disease severity and outcome. Whether endogenous EPO levels are prospectively associated with the development of HF or cardiovascular events in the general population is unknown.', 'Serum EPO levels were measured at baseline in 6686 subjects enrolled in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) study. Mean age (±SD) was 53 ± 12 years, 49.8% were male, and the median (interquartile range) EPO level was 7.7 (5.9-10.2) IU/L. During a median follow-up of 8.3 (7.7-8.8) years, 209 (3.1%) subjects were newly diagnosed with HF, 97 (1.5%) died of a cardiovascular cause, and 386 (6.0%) subjects had a non-fatal cardiovascular event (277 cardiac events and 93 strokes). Each doubling of EPO level was multivariably associated with new-onset HF [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.03-1.69, P = 0.031]. EPO levels showed interaction with urinary albumin excretion (P = 0.006) and were only associated with HF in subjects with albuminuria (HR 1.51, 95% CI 1.13-2.03, P = 0.005). There was an independent association of EPO levels with stroke in women (HR 1.82, 95% CI 1.24-2.65, P = 0.002), but not in men. No association was observed for EPO levels with other cardiovascular events or cardiovascular mortality.'] |
['In anesthetized patients, electro-acupuncture (EA) has been found to reduce sevoflurane-induced suppression of cranial and spinal motor responses to surgery without influencing the level of anesthesia. The underlying mechanisms are unclear. In the present study, blood samples were analyzed to evaluate if the increased clinical motor responses to surgery in patients subjected to EA under sevoflurane anesthesia are also reflected in higher plasma levels of catecholamines, adrenocorticotrophic hormone (ACTH), or cortisol.', 'Blood samples were obtained before anesthetic induction, soon after the study or control procedures had been completed under general anesthesia, and after 30 minutes of surgery under steady-state anesthesia with 1.8% of sevoflurane, in 45 healthy female patients, scheduled for sterilization by laparoscopy, randomized for bilateral 2 Hz-burst EA (study group; n = 22) or control (control group; n = 23) procedures.', 'Plasma levels of adrenaline were found to approach the higher preanesthetic level after 30 minutes of surgery in patients given EA stimulation but to remain low in control patients (P < 0.05)-in agreement with the stronger clinical motor responses to skin incision in the EA group. Plasma levels of noradrenaline, ACTH, and cortisol did not change in or differ between the two groups.'] |
['Prolonged tadalafil administration in men with erectile dysfunction is associated with increased testosterone (T): estradiol (E(2)) ratio mainly related to reduction of E(2) levels.', 'To investigate the presence of phosphodiesterase type 5 (PDE5) isoenzyme in primary human visceral adipocytes and whether different PDE5 inhibitors (PDE5i) could directly modulate aromatase (ARO) expression in differentiated human visceral adipocytes in culture.', 'PDE5 mRNA and protein expression in primary human visceral adipocytes as well as mRNA and protein expression of ARO, with functional activity after selective PDE5 blockade by tadalafil and sildenafil.', 'Purified primary human visceral pre-adipocytes were differentiated ex vivo and were exposed to tadalafil or sildenafil (1 µM) for different intervals of time (6-12-24-96 hours). ARO mRNA content and expression were measured by Western Blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR), respectively. T and E(2) in supernatants were measured by ELISA also in the presence of letrozole.', 'Differentiated adipocytes were found to express detectable levels of PDE5 transcripts. Acute exposure (6 hours) to both PDE5i tadalafil and sildenafil increased ARO mRNA expression by 4.7- and 2.8-fold, respectively (P < 0.001). ARO mRNA and protein levels were increased by the treatment with PDE5i in a time- and dose-dependent manner. Such effect was mimicked by 8-bromo-cGMP but was lost after 24 and 96 hours; differently, the PDE3B specific inhibitor milrinone (1 µM), displayed no effect. Accordingly, long-term exposure (24 and 96 hours) to PDE5i caused a significant increase in E(2) concentrations in the supernatant (1.7 and 2 fold, respectively; P < 0.001), with a parallel reduction of T (15% and 30%, respectively; P < 0.001). Such effect was reversed by the co-incubation with the specific ARO-inhibitor letrozole.'] |
['To study the prevalence of hypercholesterolemia, hypertriglyceridemia and the relationship between metabolic control, pubertal status and plasma lipoprotein levels in children with diabetes mellitus.', 'A cross-sectional study was conducted on 126 subjects with type I diabetes followed at our institution. There were 57 boys and 69 girls (mean age: 13.4+/-3.4 yr; mean duration of diabetes: 7.3+/-2.1 yr), on whom fasting lipoprotein levels and pubertal status were determined. Mean glycated hemoglobin (HbA1c) of the preceding year was used in the analysis. Cholesterol (CT) and triglyceride (TG) levels were transformed into standard deviations (SD) using age dependent normal values.', '1) CT levels of DM children (mean level: +0.9+/-1.2 SD) are higher for both sexes and at each age. Sixteen percent of the cases had CT level > or =2 SD. Within the range of the HbA1c observed (9.1+/-1.2%), CT levels are not correlated with the degree of metabolic control. In contrast to non-diabetic children, CT levels of the diabetic children did not vary throughout pubertal stages. CT levels correlated highly with apolipoprotein B (r=0.79; p<0.00001 and r(2)=82%, in univariate and multivariate analysis, respectively. 2) Plasma TG levels are comparable in the diabetic children (mean level: -0.11+/-0.9 SD) and non-diabetic children. Only 5% of the diabetic children have a TG level > or =2 SD. The TG levels are significantly, but weakly, positively correlated with duration of diabetes and the degree of metabolic control (r(2)=12% and 16%, respectively, p<0.0001 for both).'] |
['This study explores whether the relationship between lower socioeconomic status and insulin resistance in adolescents is mediated by both physiological and psychological factors associated with increased cardiometabolic risk.', 'School-based longitudinal cohort study of 1222 healthy, non-Hispanic black and white teens. Parent education (PE), youth-specific Cook-Medley hostility scale, waist circumference, height, weight, pubertal status, and fasting plasma insulin (FPI) were measured and FPI reassessed 1 year later. Regression analyses utilizing bootstrapping (n=2000) were used to estimate the direct and indirect effects of PE on FPI and assess the role of hostility and adiposity while adjusting for covariates.', 'Lower PE predicted higher FPI (B=-1.52, P=.003), as did hostility (B=.19, P=.002) and adiposity (waist circumference B=.44, P<.001, BMI B=.98, P<.001). The effect of PE on FPI was mediated by both hostility and adiposity. When adiposity and hostility were accounted for, the effect of PE on FPI decreased by 32% (B=-1.04, P=.04); the total indirect estimate was -.485 (95% CI, -.652, -.041). Hostility accounted for 36% of the meditational effect.'] |
['To achieve a better understanding of the repertoire of receptor tyrosine kinases (RTKs) in adult retinal ganglion cells (RGCs) we performed polymerase chain reaction (PCR), using degenerate primers directed towards conserved sequences in the tyrosine kinase domain, on cDNA from isolated single RGCs univocally identified by retrograde tracing from the superior colliculi.', 'All the PCR-amplified fragments of the expected sizes were sequenced, and 25% of them contained a tyrosine kinase domain. These were: Axl, Csf-1R, Eph A4, Pdgfrbeta, Ptk7, Ret, Ros, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3. Non-RTK sequences were Jak1 and 2. Retinal expression of Axl, Csf-1R, Pdgfrbeta, Ret, Sky, TrkB, TrkC, Vegfr-2, and Vegfr-3, as well as Jak1 and 2, was confirmed by PCR on total retina cDNA. Immunodetection of Csf-1R, Pdgfralpha/beta, Ret, Sky, TrkB, and Vegfr-2 on retrogradely traced retinas demonstrated that they were expressed by RGCs. Co-localization of Vegfr-2 and Csf-1R, of Vegfr-2 and TrkB, and of Csf-1R and Ret in retrogradely labelled RGCs was shown. The effect of optic nerve transection on the mRNA level of Pdgfrbeta, Csf-1R, Vegfr-2, Sky, and Axl, and of the Axl ligands Gas6 and ProteinS, was analysed. These analyses show transection-induced changes in Axl and ProteinS mRNA levels.'] |
['Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD.', 'In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score.', 'L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference.'] |
['Microarrays are a popular tool used in experiments to measure gene expression levels. Improving the reproducibility of microarray results produced by different chips from various manufacturers is important to create comparable and combinable experimental results. Alternative splicing has been cited as a possible cause of differences in expression measurements across platforms, though no study to this point has been conducted to show its influence in cross-platform differences.', "Using probe sequence data, a new microarray probe/transcript annotation was created based on the AceView Aug05 release that allowed for the categorization of genes based on their expression measurements' susceptibility to alternative splicing differences across microarray platforms. Examining gene expression data from multiple platforms in light of the new categorization, genes unsusceptible to alternative splicing differences showed higher signal agreement than those genes most susceptible to alternative splicing differences. The analysis gave rise to a different probe-level visualization method that can highlight probe differences according to transcript specificity."] |
['Prostanoids have been shown to improve exercise tolerance, hemodynamics and quality of life in patients with pulmonary arterial hypertension (PAH). We investigated whether treprostinil exerts direct contractile effects on cardiomyocytes that may explain partly the beneficial effects of these drugs.', 'Ventricular cardiomyocytes from adult rats were paced at a constant frequency of 0.5 to 2.0 Hz and cell shortening was monitored via a cell edge detection system. Twitch amplitudes, expressed as percent cell shortening of the diastolic cell length, and maximal contraction velocity, relaxation velocity, time to peak of contraction and time to reach 50% of relaxation were analyzed.', 'Treprostinil (0.15 - 15 ng ml(-1)) slightly increased contractile dynamics of cardiomyocytes at clinically relevant concentrations. However, the drug significantly improved cell shortening of cardiomyocytes in the presence of isoprenaline, a beta-adrenoceptor agonist. Treprostinil exerted this effect at all beating frequencies under investigation. Treprostinil mimicked this potentiating effect in a Langendorff preparation as well. The potentiating effect of treprostinil on isoprenaline-dependent cell shortening was no longer seen after phosphodiesterase inhibition. Long-term cultivation of cardiomyocytes with treprostinil did not modify load free cell shortening of these cells, but reduces the duration of contraction.'] |
['Inositol hexaphosphate (IP(6)) is a well-known inhibitor of iron absorption, whereas the effects of the less-phosphorylated derivatives of IP(6) are less known.', 'The objective was to investigate the effects of inositol tri-, tetra-, and pentaphosphates (IP(3), IP(4), and IP(5), respectively) on iron absorption in humans.', 'Iron absorption was measured in 5 experiments from single meals by extrinsic labeling with (55)Fe and (59)Fe and determination of whole-body retention and the erythrocyte uptake of isotopes. In experiments 1-3 the meals contained white-wheat rolls to which 10 mg P as IP(5), IP(4), or IP(3), respectively, was added. Inositol 1,2,6-triphosphate [Ins(1,2, 6)P(3)] and a mixture of isomers of IP(4) and IP(5) were studied. White-wheat rolls contained 10 mg P as IP(3) + IP(4) and 2 mg P as IP(5) + IP(6) in experiment 4 and 20 mg P as IP(3) + IP(4) and 3 mg P as IP(5) + IP(6) in experiment 5; inositol phosphates were obtained via fermentation of sodium phytate. Each experiment had 8-11 subjects.', 'In experiment 1, iron absorption was reduced by 39%, whereas there was no significant effect on iron absorption in experiments 2 and 3. In experiments 4 and 5, iron absorption was reduced by 54% and 64%, respectively, suggesting that IP(3) and IP(4) contributed to the inhibitory effect.'] |
['Endoscopic biliary stenting is often used for large or difficult common bile duct (CBD) stones that cannot be extracted at one session. We compared the sizes of the CBD stones after a period of stenting.', 'Over a 6-year period, a total of 444 patients with large CBD stones (> 2 cm diameter) or difficult CBD stones were managed in our endoscopy unit, of which 46 were treated by endoscopic stenting. Twenty-eight had second ERCP for stone removal after a median period of 63 days (range 17-1002 days). The largest diameter of the stones and the CBD (after correction of magnification) before and after stenting were compared using the Wilcoxon signed test.', 'Before stenting the largest diameters of CBD stones were 11-46 mm (mean 24.9 mm) and decreased to 5-46 mm (mean 20.1 mm) after stenting. The difference in stone sizes was statistically significant although the CBD diameter pre- and post-stenting was not significantly different. The reduction in stone sizes was not significantly correlated with the duration of stenting.'] |
['Septicemia activates coagulation and decreases activated protein C (APC). Low APC in adults is associated with multiorgan dysfunction and mortality, but such data in neonates are lacking. Being deficient in APC, neonates may be especially vulnerable to the effects of low APC.', 'This cohort study was conducted on 40 neonates with severe bacterial septicemia to determine the relationship between plasma APC values and mortality, time to mortality, and hazard of dying. Low birth weight neonates with sepsis, organ dysfunction, and systemic inflammatory response syndrome were enrolled after parental consent. Plasma APC was assayed at enrollment and subjects were followed for 14 days from enrollment. Low birth weight neonates, who had major malformations, severe birth asphyxia, or received blood products before APC assay, were excluded.', 'comparison of APC level between survivors and nonsurvivors.', 'survival with low versus normal APC; and hazard ratio of APC, adjusted for birth weight, Score for Neonatal Acute Physiology and number of affected organs.', 'Forty of 74 eligible neonates were included. Twenty-five of the enrolled neonates died within 14 days. APC levels in nonsurvivors were lower than in survivors [median (interquartile range) %, 15 (4.5-21) versus 33 (18-55); P < 0.001]. Ten nonsurvivors versus 1 survivor had low APC (P = 0.03). Positive predictive value (PPV) of low APC values for mortality was 90.9%. Survival in the low APC group (n = 11) was shorter than in normal APC group [median (95% confidence interval) days, 3 (2.3-3.7) versus 10, P value <0.001]. APC value was independently associated with hazard of dying [adjusted risk 0.95 (95% confidence interval 0.92-0.99), P = 0.02]. Each 1% rise in APC decreased the hazard of dying by 5%.'] |
['Boehmeria nivea (Linn.) Gaudich (Urticaceae), a natural herb, has a long history of treating several diseases including wound healing. However, the anti-inflammatory effect of B. nivea has not been investigated.', 'We investigated whether the 70% ethanol extract of B. nivea (Ebn) can exert anti-inflammatory activity. Several phenolic compounds of extracts were determined to provide further information on the correlation between anti-inflammatory effects and phenolic compounds.', 'We prepared a 70% ethanol extract of B. nivea leaves and evaluated its anti-inflammatory activity (200, 400, 800, 1200\u2009µg/mL) by measuring the secretions of nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), which were stimulated by lipopolysaccharide (LPS) in RAW264.7 macrophages. The total phenolic compounds were determined by the Folin-Ciocalteu method and major compounds were determined by HPLC.', 'Ebn was able to abolish the LPS-induced secretions of NO, TNF-α and IL-6. It also decreased the protein levels (IC₅₀\u2009=\u2009186\u2009µg/mL) of LPS-induced inducible nitric oxide synthase (iNOS). The LPS stimulated p38, JNK and ERK phosphorylations significantly more than the controls. Surprisingly, although Ebn reduced p38 and JNK phosphorylations, it did not influence ERK phosphorylation. We found that Ebn revealed several major compounds such as chlorogenic acid (1.96\u2009mg/100\u2009g), rutin (46.48\u2009mg/100\u2009g), luteolin-7-glucoside (11.29\u2009mg/100\u2009g), naringin (1.13\u2009mg/100\u2009g), hesperidin (23.69\u2009mg/100\u2009g) and tangeretin (1.59\u2009mg/100\u2009g).'] |
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