bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central Role of Rho Kinase in Lipopolysaccharide-Induced Platelet Capture on Venous Endothelium
Authors: Slotta Jan E. , Braun Oscar Ö. , Menger Michael D. , Thorlacius Henrik 
Published: May 2016

Background Platelet-endothelial cell interactions play a key role in hemostasis and pathological coagulation and are dependent on different surface molecules that are expressed upon activation (eg, mediated by lipopolysaccharide [LPS]). Recently, we have shown that Rho kinase plays a central role in LPS-mediated leukocyte-endothelial cell interactions. We investigated the role of Rho-kinase in inflammatory interactions between platelets and the endothelium in femoral veins in vivo. Methods Mice were injected intravenously with LPS (0.5 mg/kg)/D-galactosamine (900 mg/kg), and Rho kinase was blocked with fasudil 15 minutes before LPS application. Four hours after LPS administration, intravital fluorescence microscopy of the femoral vein was performed, and primary and secondary platelet-endothelial cell interactions were visualized after in vivo platelet staining with rhodamine 6G. Results Intravital microscopy showed a significant increase in platelet tethering, rolling, and firm adhesion as well as platelet secondary capture in LPS-treated mice. Rho-kinase inhibition by fasudil significantly reduced platelet tethering, rolling, and firm adhesion. Interestingly, functional blockade of Rho kinase was also able to diminish secondary platelet capture by 79%. Conclusions From our data, we conclude that Rho-kinase signaling plays a central role in the regulation of LPS-induced platelet-endothelial cell interactions in large veins in vivo. Thus, Rho-kinase inhibition might be useful in prevention or treatment of pathological inflammation and endotoxin-mediated hypercoagulation.
Effects of Additive Therapy with Spironolactone on Proteinuria in Diabetic Patients Already on ACE Inhibitor or ARB Therapy: Results of a Randomized, Placebo-Controlled, Double-Blind, Crossover Trial
Authors: Saklayen Mohammad G. , Gyebi Leonard K. , Tasosa Joseph , Yap Jayson 
Published: May 2016

Introduction Aldosterone seems to have deleterious effects on the kidneys. Many animal studies and a few clinical trials have shown that suppression of aldosteroneby aldosterone receptor blockers ameliorates these effects. Method In a double-blind crossover study, patients with diabetic nephropathy who were already receiving either angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) were given spironolactone or matching placebo with 1 month of washout in between. Blood pressure (BP), serum creatinine, serum potassium, and spot urine protein/creatinine were measured at the beginning and end of each study period. Results Mean systolic BP on spironolactone went down from 153.64 (±25.95) at the beginning to 141.60 (±16.54) at the end of study ( P = 0.01). Diastolic BP during spironolactone therapy did not change significantly. The urine protein/creatinine increased from 1.24 (±1.13) to 1.57 (±2.13) on placebo ( P = 0.35) and decreased from 1.80 (±1.78) to 0.79 (±0.99) during spironolactone therapy ( P = 0.004). In other words proteinuria increased by 24% during the placebo treatment period but decreased by half (57%) during the active treatment. Serum potassium increased from 4.29 (±0.47) to 4.64 (±0.55) during spironolactone therapy ( P = 0.002), no significant change with placebo. Whereas serum creatinine did not change on placebo, it increased from 1.35 (±0.54) to 1.56 (±0.62) on spironolactone ( P = 0.006). Glomerular filtration rate decreased from 61.91 (±23.4) to 53.94 (±23.58) on spironolactone ( P = 0.0001) but not on placebo. Conclusions Addition of a modest dose of spironolactone to a regimen of ACEI or ARB in patients with diabetic proteinuria causes further reduction in proteinuria and also lowers the systolic BP. As with ACEI or ARB, spironolactone modestly reduces the glomerular filtration rate and raises serum potassium.
Do Surrogate Markers for Adiposity Relate to Cytokines in Adolescents?
Authors: Rubin Daniela A. , McMurray Robert G. , Harrell Joanne S. , Hackney Anthony C. , Haqq Andrea M. 
Published: May 2016

Purpose To determine the associations between field-collected surrogates of adiposity and concentrations of resistin, tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and adiponectin in youth. Methods Cross-sectional data from 60 normal weight and 60 overweight adolescents, ages 10-14 years, were retrospectively examined. Body mass index (BMI) percentile, sum of subscapular and triceps skinfolds (SSF), and waist circumference (WC) were used to classify weight status (BMI) or adiposity (SSF and WC). Percentiles for each surrogate were used for comparison groups. Fasting TNF-α, IL-6, resistin, and adiponectin concentrations were measured in plasma. Results Multiple regression models, controlling for sex and ethnicity, indicated that TNF-α was associated with BMI percentile ( R2 = 0.107, P < 0.05) and SSF ( R2 = 0.085, P < 0.05), whereas resistin was associated with SSF ( R2 = 0.118, P < 0.05). Adiponectin was associated with all 3 adiposity markers: BMI percentile ( R2 = 0.298, P < 0.05), SSF ( R2 = 0.297, P < 0.05), and waist ( R2 = 0.278, P < 0.05). Analyses of variance indicated higher TNF-α and lower adiponectin concentrations in youth with a BMI higher than the 95th percentile ( P = 0.014; P < 0.001) or SSF higher than the 95th percentile ( P = 0.025; P < 0.001). Youth with WC higher than the 90th percentile had higher resistin ( P = 0.029), higher IL-6 ( P = 0.028), and lower adiponectin ( P < 0.001) concentrations. Conclusions Of the 3 surrogates examined, differences in cytokine concentrations were mostly observed in youth who had WC percentiles higher than the 90th percentiles versus WC lower than the 75th percentiles. Alternatively, from the multiple-regression models SSF, an estimate of subcutaneous adiposity was the surrogate most consistently related to all cytokines, although the degrees of associations were low. The results suggest that although some surrogates were more strongly associated to certain cytokines, WC and SSF seemed more closely associated with cytokines than a BMI percentile indicating obesity.
Evaluation of Risk Factors and Seroprevalence of Hepatitis B and C in Diabetic Patients in Kutahya, Turkey
Authors: Gulcan Aynur , Gulcan Erim , Toker Aysun , Bulut &Idot;smet , Akcan Yusuf 
Published: May 2016

Aim To assess the prevalence of hepatitis B and C viruses among Turkish patients with type 1 and type 2 diabetes mellitus and to determine the risk factors affecting the prevalence in these patient groups. Methods This study included 630 diabetic and 314 nondiabetic patients. Serologic testing for anti-hepatitis C virus (anti-HCV) and HbsAg was done using a third-generation commercial enzyme-linked immunosorbent assay, and samples positive for anti-HCV and HbsAg were confirmed by a polymerase chain reaction assay. Diabetic patients were classified by HbsAg and anti-HCV status and were evaluated according to demographic features, diabetic characteristics and nondiabetic general risk factors, harmful habits, and aminotransferase (alanine aminotransferase and aspartate aminotransferase) levels. Results HbsAg and anti-HCV seropositivity rates were 5.1% and 3.2% in diabetic patients and were 3.8% and 1.3% in control group, respectively. There was no statistically significant difference between the 2 groups with respect to either marker. Shared risk factors for both hepatitis infections were increased aminotransferase levels and history of hospital admission. In addition, long duration of diabetes mellitus, poor diabetic regulation, and insulin treatment usage were found to relate to HbsAg, whereas a history of blood transfusions and surgical procedures were found to associate with anti-HCV seropositivity. Conclusions We determined that hepatitis B virus and hepatitis C virus infections were slightly but not significantly higher in diabetic patients compared with a normal population. If it is considered that different results might be obtained in various countries or even in various regions of same country, it may be concluded that multicenter and comprehensive studies are needed to elucidate true infection rates and to identify other risk factors affecting the prevalence of these infections.
Reporting of Multivariable Methods in the Medical Literature
Authors: Tetrault Jeanette M. , Sauler Maor , Wells Carolyn K. , Concato John 
Published: May 2016

Background Multivariable models are frequently used in the medical literature, but many clinicians have limited training in these analytic methods. Our objective was to assess the prevalence of multivariable methods in medical literature, quantify reporting of methodological criteria applicable to most methods, and determine if assumptions specific to logistic regression or proportional hazards analysis were evaluated. Methods We examined all original articles in Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine, from January through June 2006. Articles reporting multivariable methods underwent a comprehensive review; reporting of methodological criteria was based on each article's primary analysis. Results Among 452 articles, 272 (60%) used multivariable analysis; logistic regression (89 [33%] of 272) and proportional hazards (76 [28%] of 272) were most prominent. Reporting of methodological criteria, when applicable, ranged from 5% (12/265) for assessing influential observations to 84% (222/265) for description of variable coding. Discussion of interpreting odds ratios occurred in 13% (12/89) of articles reporting logistic regression as the primary method and discussion of the proportional hazards assumption occurred in 21% (16/76) of articles using Cox proportional hazards as the primary method. Conclusions More complete reporting of multivariable analysis in the medical literature can improve understanding, interpretation, and perhaps application of these methods.
Tumor Necrosis Factor α-308 and -238 Polymorphisms in Rheumatoid Arthritis. Association with Messenger RNA Expression and sTNF-α
Authors: Oregón-Romero Edith , Vázquez-Del Mercado Mónica , Ruiz-Quezada Sandra Luz , Navarro-Hernández Rosa Elena , Rangel-Villalobos Héctor , Martínez-Bonilla Gloria , Bernard-Medina Ana Guilaisne , Armendáriz-Borunda Juan , García-Bañuelos Jesús , Muñoz-Valle José Francisco 
Published: May 2016

Background Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor α (TNFα). We investigated the relationship of TNFα-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFα (sTNFα) in 50 RA and 100 healthy subjects (HS). Methods Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFα-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFα was quantified by real-time polymerase chain reaction. The sTNFα levels were measured by enzyme-linked immunosorbent assay. Results The TNFα-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS ( P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS ( P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFα-238 polymorphism. Rheumatoid arthritis patients showed high TNFα mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFα levels in both TNFα polymorphisms. The correlation of sTNFα levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed. Conclusion The TNFα-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFα expression.
ACE Insertion/Deletion, but Not −240A>T Polymorphism, Modulates the Severity in Heart Failure
Authors: Fatini Cinzia , Sticchi Elena , Marcucci Rossella , Said Abdihakim Abdullahi , Del Pace Stefano , Verdiani Valerio , Nozzoli Carlo , Gensini Gian Franco , Abbate Rosanna 
Published: May 2016

Objective ACE gene is reported to be a candidate gene in heart failure. The insertion/deletion (I/D) polymorphism has been observed to be a predictor of mortality in this disease, but no data are available concerning the role of ACE −240A>T polymorphism. In this study, we investigated the role of ACE I/D and −240A>T polymorphisms in influencing both severity and clinical outcomes in patients with heart failure, according to New York Heart Association (NYHA) class. Patients We studied 323 patients with heart failure (258 men/65 women; age, 70.8 ± 11.5 years) followed-up for 11.9 ± 6.6 months. Results The ACE D and −240T allele frequency significantly increased according to the NYHA functional class ( P = 0.0002 and P < 0.0001, respectively). No significant difference in ACE polymorphism genotype distribution and allele frequency according to N-terminal pro-brain natriuretic peptide tertiles was observed. At multinomial regression analysis, ACE D but not −240T allele has been evidenced to be a significant and independent predictor of severity for both NYHA III and IV classes ( P = 0.01 and P = 0.004, respectively). The ACE D allele prevalence was higher, even if not significantly in both death and rehospitalization groups in comparison with survivors and nonrehospitalized ( P = 0.6 and P = 0.9, respectively). No difference in −240T allele frequency has been observed for the ACE −240A>T polymorphism, in relation to both death and rehospitalization ( P = 0.1 and P = 0.6, respectively). Conclusions This study suggests that ACE I/D polymorphism might represent a predisposing factor to severe heart failure, independently of well-known prognostic markers.
Medical Student Research Exposure via a Series of Modular Research Programs
Authors: Langhammer Christopher G. , Garg Karan , Neubauer Judith A. , Rosenthal Susan , Kinzy Terri Goss 
Published: May 2016

Background The falling percentage of doctors of medicine applying for National Institute of Health-funded research grants is 1 indicator that physician-scientists are a disappearing breed. This is occurring at a time when increased translational, disease-oriented, patient-oriented, and clinical research are national goals. One of the keys to providing sufficient numbers of physician-scientists to support this goal is the active targeting of medical students. We hypothesize that an improved research program infrastructure and responsiveness to changing student needs will increase student participation in research-oriented electives. Methods We have developed a student research program consisting of 2 Students Interested in Research noncredit electives (lecture and laboratory based), summer fellowships, support for year-out fellowships, and a Distinction in Research program that spans undergraduate medical education. Student participation and short-term research outcomes from fall 2004 through spring 2008 are analyzed to examine program efficacy. Results Students involved in the early parts of the program initially experienced higher application and success rates for summer funding opportunities, but as the program has matured, these rates have fallen in line with the class average. Independently, students participating in later portions of the program increasingly submit or publish a first author paper and have taken a year off for research during medical school. Overlap of participation in the programs is generally smaller than expected. Conclusion Although structured programs can provide step-wise research experiences of increasing intensity, students may not experience a training pipeline in which each stage relies on those before and after, and instead may sample an a la carte selection of research-based enrichment opportunities.
Effect of Statins on Fasting Plasma Glucose in Diabetic and Nondiabetic Patients
Authors: Sukhija Rishi , Prayaga Sastry , Marashdeh Mohammad , Bursac Zoran , Kakar Priyanka , Bansal Darpan , Sachdeva Rajesh , Kesan Sree Hari , Mehta Jawahar L. 
Published: May 2016

Background The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) reduce serum cholesterol level and cardiovascular morbidity and mortality. However, the effect of statins on glucose metabolism is unclear. Some studies have suggested that statins may cause hyperglycemia by increasing calcium concentration in the islet cells leading to decrease in insulin release or by decreasing GLUT 4-mediated peripheral glucose uptake. Methods We analyzed the data in 345,417 patients (mean age 61 ± 15 years, 94% males, 6% diabetic, 20% statin users) from the Veterans Affairs VISN 16 database. We studied change in fasting plasma glucose (FPG) in this population over a mean time of 2 years between the first available measurement and the last measurement form the most recent recorded visit. Data were limited to patients who had 2 FPG measurements. Diagnosis of diabetes had to be present before the first FPG measurement. Results Among patients without diabetes, FPG increased with statin use from 98 mg/dL to 105 mg/dL, and among nonstatin users, FPG increased from 97 mg/dL to 101 mg/dL (increase in FPG with statin use P < 0.0001). Among patients with diabetes, FPG increased with statin use from 102 mg/dL to 141 mg/dL, and among nonstatin users, FPG increased from 100 mg/dL to 129 mg/dL (increase in FPG with statin use; P < 0.0001). After adjustment for age and use of aspirin, β-blockers, and angiotensin-converting enzyme inhibitors, the change in FPG in nondiabetic statin users was 7 mg/dL (vs 5 mg/dL in nonstatin users, P < 0.0001) and for diabetic statin users it was 39 mg/dL (vs 32 in nonstatin users, P < 0.0001). Conclusions Statin use is associated with a rise of FPG in patients with and without diabetes. This relationship between statin use and rise in FPG is independent of age and use of aspirin, β-blockers, and angiotensin-converting enzyme inhibitors.
Inhibition of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme a Reductase Reduces Leukocyte Recruitment and Hepatocyte Apoptosis in Endotoxin-Induced Liver Injury
Authors: Slotta Jan E. , Laschke Matthias W. , Wang Yusheng , Schilling Martin K. , Menger Michael D. , Thorlacius Henrik 
Published: May 2016

Background Endotoxemia is well known to be associated with an excessive host response to bacteria or microbial compounds, resulting in systemic inflammation and organ injury. The aim of the present study was to examine the effects of simvastatin on endotoxemic liver injury. Methods Male C57BL/6J mice were challenged intraperitoneally with 0.5 mg/kg Escherichia coli-lipopolysaccharide (LPS) and 0.9 g/kg d-galactosamine (Gal). Mice were pretreated with 0.2 mg/kg simvastatin. Lipopolysaccharide/d-Gal-injected mice without simvastatin served as endotoxemic controls, and sham mice served as negative controls. Additional mice were challenged with LPS/d-Gal and co-treated with simvastatin and 10 mg/kg mevalonate to determine the role of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. After 6 hours of endotoxemia serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as caspase-3 and myeloperoxidase activity were determined. Results Endotoxemia caused a substantial hepatocellular injury as indicated by significantly elevated serum ALT and AST levels and hepatocellular apoptosis. Leukocyte infiltration in the liver was significantly elevated in endotoxemic mice. Simvastatin significantly reduced endotoxin-induced hepatocellular damage and apoptosis. Moreover, hepatic accumulation of leukocytes was attenuated by simvastatin in endotoxemic animals. Co-administration of mevalonate abolished protective effects of simvastatin on endotoxin-provoked increases in ALT, AST, and hepatocellular apoptosis as well as leukocyte recruitment. Conclusions Simvastatin has the capacity to prevent endotoxemic liver injury by inhibiting leukocyte infiltration and hepatocellular apoptosis. These protective effects exerted by simvastatin are dependent on the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase pathway. Thus, simvastatin may represent a potential approach to prevent endotoxemia-associated liver dysfunction.
Changes of Red Blood Cell Surface Markers in a Blood Doping Model of Neocytolysis
Authors: Chang Chung-Che , Chen Yayan , Modi Kapil , Awar Omar G. , Alfrey Clarence P. , Rice Lawrence 
Published: May 2016

Background Neocytolysis, the selective hemolysis of young circulating red blood cells (RBCs), contributes to the physiologic control of red cell mass and to pathophysiologic phenomena such as anemia of renal disease, anemia after spaceflight, and blood doping by athletes. Progress in understanding the process is hampered by the lack of established markers to distinguish young from older RBC. Methods Twelve potentially informative RBC surface markers were assayed by flow cytometry in normal blood samples, and 4 were preferentially expressed in young RBC. To create a model of neocytolysis, 3 normal volunteers had recombinant human erythropoietin (rhEpo) administered until mild erythrocytosis occurred, then were studied upon rhEpo withdrawal. Results Neocytolysis ensued that most evident from a rapid rise in serum ferritin as the iron from young RBC was transferred back to stores. Five additional volunteers had surface markers monitored during and after rhEpo administration. Three subjects with marginal baseline iron stores had blunted response to rhEpo, no significant neocytolysis, and no change in RBC surface marker expression. Two subjects with adequate baseline iron stores developed erythrocytosis followed by neocytolysis. Decreased expression of CD44 (homing-associated cell adhesion molecule) and CD71 (transferrin receptor) seemed to correlate best with neocytolysis; CD35 (complement receptor) less so. Of note, further studies are needed to determine if these changes are causative of red cell destruction. Conclusion This study begins to establish a human model of neocytolysis, to establish markers differentiating young and old RBC, and to establish a basis for better definition of the process. Although our study is preliminary, the results support the possibility that flow could be useful to detect blood doping because neocytolysis should predictably occur in athletes who surreptitiously blood dope.