bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin 1, Interleukin 6, Interleukin 10, and Tumor Necrosis Factor α in Active and Quiescent Systemic Lupus Erythematosus
Authors: Cigni Alessandro , Pileri Piera Veronica , Faedda Rossana , Gallo Paola , Sini Annalisa , Satta Andrea Ercole , Marras Riccardo , Carta Elisabetta , Argiolas Davide , Rum Iolanda , Masala Antonio 
Published: May 2016

Objectives Several studies have investigated the cytokine profile of patients with systemic lupus erythematosus (SLE); however, their role is still controversial, mostly because SLE has a heterogeneous disease manifestation. We measured 4 of the most important cytokines in patients with SLE after dividing them in uniform groups according to disease activity and organ involvement. Materials and Methods Eighty-two adult female patients with SLE were divided into 3 groups according to disease activity and organ involvement: Group A (SLE activity index [SLEDAI] score, 7 ± 0.4) included subjects with newly diagnosed, active SLE, investigated before starting therapy. Group B (SLEDAI score, < 6) included patients without renal involvement, treated with prednisone and azathioprine or hydroxychloroquine. Group C (SLEDAI score, < 6) included patients with lupus nephritis, treated with methylprednisolone and cyclophosphamide, reaching complete remission. Fourteen healthy females served as controls. Results Interleukin-1 levels were 1.0, 0.8, 0.7, and 0.25 pg/mL in groups A, B, C, and D, respectively. Interleukin-6 levels were 3.2, 3.6, 4.0, and 1.4 pg/mL in groups A, B, C, and D, respectively; Il-10 levels, 3.05, 1.1, 1.5, and 1.65; tumor necrosis factor-α levels, 8.75, 5.8, 5.4, and 3.6. Interleukin 1, IL-6, and tumor necrosis factor-α were significantly higher in the patients with SLE than in the healthy controls; IL-1 was significantly higher in group A than in group C. Interleukin 10 showed positive correlation with C-reactive protein, whereas it showed negative correlation with C3. Conclusions Data from our cohort, one of the largest so far reported, add to the evidence that proinflammatory cytokines such as Interleukin-1, Interleukin-6, Interleukin-10 and tumor necrosis factor-α are important in SLE pathogenesis.
Improvement in Insulin Sensitivity and Dyslipidemia in Protease Inhibitor-Treated Adult Male Patients after Switch to Atazanavir/Ritonavir
Authors: Busti Anthony J. , Bedimo Roger , Margolis David M. , Hardin Dana S. 
Published: May 2016

Background Treatment of human immunodeficiency virus (HIV) with protease inhibitors (PIs) is associated with insulin resistance, triglyceride-rich dyslipidemia, and fat redistribution. Atazanavir (ATV), a potent once-daily PI, has been recognized for its convenience to patients, and some studies describe improved lipid metabolism. However, its effects on insulin sensitivity have not been elucidated. We conducted this study to test the hypothesis that ATV improves insulin resistance and dyslipidemia. Methods We prospectively studied 9 HIV-infected men with dyslipidemia (median age, 53 years; baseline triglyceride level, >200 mg/dL) on stable PI-containing antiretroviral therapy who elected to change PI therapy to ritonavir-boosted ATV therapy, dose of 300/100 mg. We measured insulin resistance at baseline and after 12 weeks of therapy using a hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m2 minute). Fasting lipid profiles and body composition (whole-body dual energy x-ray absorptiometry) were also measured at baseline and after 12 weeks. Results All 9 patients completed the study and maintained undetectable viral loads (<50 copies/mL) and stable CD4 counts. After 12 weeks, insulin sensitivity significantly improved (+28%; P = 0.008) in all patients. Triglyceride levels also improved. Conclusions Using the gold-standard euglycemic clamp, ritonavir-boosted ATV therapy improved PI-induced insulin resistance among dyslipidemic HIV-infected men on PI-based antiretroviral therapy. These findings were not attributable to a change in body weight and provide further evidence for ATV's unique metabolic profile among the PIs.
Renal Injury, Abnormal Vitamin D Metabolism and Bone Homeostasis in Aged Rats with Insulin Resistance or Type 2 Diabetes Mellitus
Authors: Chang-Quan Huang , Bi-Rong Dong , Qian Xiao , Ping He , Qun-Fang Ding , Zhen-Chan Lu , Xiao-Dong Peng 
Published: May 2016

Objective The study aimed to explore the relationship among renal injury, abnormal vitamin D metabolism, and bone homeostasis in insulin resistance (IR) or type 2 diabetes mellitus (T2DM). Design and Methods The animal models of IR, T2DM, and T2DM treated with 1-alpha hydroxyvitamin D (1-α(OH)D) were established on 18-month-old male Wistar rats. Glucose infusion rates (GIR) and levels of urinary albumin (UA), serum 25-hydroxyvitamin D (25-(OH)D), serum 1,25-dihydroxyvitamin D (1,25-(OH)2D), and bone mineral density (BMD) in lumbar vertebrae and femoral bone were measured. Results Urinary albumin level in the rats with T2DM significantly increased, and there existed a significant and negative correlation between GIR and UA level in the rats with T2DM or IR. The levels of serum 25-(OH)D in all models were similar. The levels of serum 1,25-(OH)2D and BMD in the rats with IR were significantly higher than those in the rats with T2DM and were lower than those in normal control rats. In the aged rats with T2DM, administration of 1-α(OH)D had no effect on serum 25-(OH)D level although significantly increased the levels of serum 1,25-(OH)2D and BMD. There existed a negative correlation between the levels of serum 1,25-(OH)2D and UA in the rats with T2DM or IR. Conclusions In IR or T2DM, abnormal vitamin D metabolism is characterized by 1,25-(OH)2D deficiency and is related to renal injury, and there also existed bone loss. In T2DM, both 1,25-(OH)2D deficiency and bone loss can be reversed by 1-α(OH)D.
Acute Suppression of Circulating sCD40L during Hyperglycemia and Euglycemic-Hyperinsulinemia in Healthy Young Males
Authors: Oliver Stacy R. , Flores Rebecca L. , Pontello Andria M. , Rosa Jaime S. , Zaldivar Frank P. , Galassetti Pietro R. 
Published: May 2016

sCD40L is a proatherogenic cytokine, part of the tumor necrosis factor (TNF) superfamily and consistently associated with obesity, diabetes, and increased cardiovascular risk. Although the role of sCD40L in the onset/progression of cardiovascular complications of dysmetabolic diseases may be modulated by acute and/or chronic fluctuations of plasma insulin and glucose, very little has been done to clarify this interaction. The kinetic profile of sCD40L (and, in an exploratory manner, of several immunomodulatory factors), were measured during hyperglycemia and euglycemic-hyperinsulinemia in a group of 10 healthy young males (26.8 ± 1.4 years). After an overnight fast, intravenous (iv) catheters were placed in antecubital veins of both arms for blood drawing and dextrose/insulin iv infusions. Procedures lasted 240 minutes including baseline ( t = 0-60), hyperglycemia ( t = 60-150; plasma glucose ∼220 mg/dL via iv dextrose infusion), and euglycemic-hyperinsulinemia ( t = 150-240; glucose infusion continued to clamp glycemic levels between 80 and 110 mg/dL; constant insulin infusion at 1.5 mU/kg/minute). Plasma for cytokine assays was sampled at 12 separate time-points. Plasma levels of sCD40L were significantly reduced ( P < 0.01) during hyperglycemia and euglycemic-hyperinsulinemia, paralleling the kinetic profiles of free fatty acids and ketone bodies. This pattern was also observed in other immunomodulatory factors (notably cortisol and epidermal growth factor), while (interleukin [IL]-1α, IL-4, IL-6, IL-9, IL-10, TNF-α, Eotaxin) did not change significantly. Significant reductions of the proatherogenic cytokine sCD40L were observed during endogenous and exogenous hyperinsulinemia, independent of prevailing glucose concentration, in young healthy males. Our data suggest a mechanism by which correct insulin action may exert a beneficial protective role against inflammation, independent of its immediate glucose-lowering effect.
Fibrogenic Polymorphisms (TGF-β, PAI-1, AT) in Mexican Patients with Established Liver Fibrosis. Potential Correlation with Pirfenidone Treatment
Authors: Armendáriz-Borunda Juan , Rincón Ana Rosa , Muñoz-Valle José Francisco , Bueno-Topete Miriam , Oregón-Romero Edith , Islas-Carbajal María Cristina , Medina-Preciado David , González-García Ignacio , Bautista C. Alfredo , García-Rocha Sergio , Godoy Jesús , Vázquez-Del Mercado Mónica , Troyo-SanRoman Rogelio , Arellano-Olivera Inmaculada , Lucano Silvia , Álvarez-Rodríguez Adriana , Salazar Adriana 
Published: May 2016

Background/Aim The aim of this work was to establish a potential correlation between specific polymorphisms and presence of hepatic fibrosis in Mexican patients with established liver fibrosis (ELF). Second, necroinflammatory index improvement was correlated with Pirfenidone (PFD) treatment response and the same polymorphisms. Methods We analyzed TGF-β polymorphisms in codon 25, a single basepair guanine insertion-deletion polymorphism (4G/5G) for PAI-1 and angiotensin AT-6 single nucleotide polymorphism located in -6 promoter region. Twenty patients infected with either hepatitis C virus (HCV) (n = 13) or affected by alcohol consumption (n= 7) were included. Thirty subjects with no hepatic damage were included in control group. Blood samples for genomic DNA were obtained and plasminogen activator inhibitor-1 polymorphisms were done by polymerase chain reaction-artificial introduction of a restriction site, TGF-β by polymerase chain reaction-amplification refractory mutation system and AT by polymerase chain reaction-restriction fragment length polymorphisms. Liver biopsies were obtained at baseline and after 12 months of PFD treatment. Results Established liver fibrosis patients had the homozygote G/G TGF-β genotype, which has been associated with increased development of fibrosis. None of our patients had the G/C genotype. All pure HCV and pure alcohol abuse subjects carried G/G TGF-β genotype (100% vs 37% control) ( P = 0.0006). The odds of having TGF-β G/G genotype was 19.5 for HCV patients and 10.83 for alcohol consumption patients as compared with healthy subjects ( P < 0.001). Established liver fibrosis patients had an improvement in necroinflammatory index after PFD treatment when correlated with plasminogen activator inhibitor-1 and angiotensinogen-6 genotypes. Conclusion Our data suggested that a combination of inherited polymorphisms increased the risk of advanced fibrosis in ELF patients. Pure HCV and pure alcohol consumption patients which were homozygous G/G carriers had 19.5- and 10.8-fold higher risk to develop advanced fibrosis respectively. Abbreviations: TGF-β, transforming growth factor β; RAS, renin angiotensin system
Advanced Glycation End Products Increase Transglutaminase Activity in Primary Porcine Tenocytes
Authors: Rosenthal Ann K. , Gohr Claudia M. , Mitton Elizabeth , Monnier Vincent , Burner Todd 
Published: May 2016

Objectives Tendon abnormalities, such as increased stiffness, thickness, and excess calcification, occur commonly in patients with diabetes mellitus and cause considerable disability. These changes are frequently attributed to increased cross-linking of extracellular matrix components by advanced glycation end-products (AGEs). However, cellular effects of AGEs, such as increased activity of the cross-linking transglutaminase (Tgase) enzymes, could also contribute to altered tissue biomechanics and calcification in diabetic tendons. We determined the effect of AGE-modified protein on tenocyte Tgase activity. Research Design and Methods Primary porcine tenocytes were exposed to Nε- carboxymethyl-lysine (CML)-modified type I collagen in high or normal glucose media. Protein and mRNA levels of the Tgase enzymes and Tgase activity levels were measured, as were markers of apoptosis. We also determined the effect of antioxidants on CML-collagen mediated Tgase activity. Results Carboxymethyl-lysine-collagen increased Tgase activity in tenocytes 2.3- to 5.6-fold over unmodified collagen controls in both normal and high glucose media, without altering enzyme protein levels. Anti-oxidant treatment reduced the effect of CML-collagen on Tgase activity. Deoxyribonucleic acid laddering and annexin V protein levels were not altered by CML-collagen exposure. Conclusions Carboxymethyl-lysine-collagen increased Tgase activity in tenocytes, likely posttranslationally. Increased levels of Tgase-mediated cross-links may contribute to the excess calcification and biomechanical pathology seen in diabetic tendons.
Effects of Diet and Gemfibrozil on Posttransplant Hyperlipidemia in Renal Transplant Recipients
Authors: Sapan Muzaffer , Ozben Beste , Yakupoglu Gulsen , Suleymanlar Gultekin , Ozben Tomris 
Published: May 2016

Background Posttransplant hyperlipidemia increases cardiovascular morbidity and mortality rate in renal transplant recipients. It also leads to graft loss due to atherosclerosis and glomerular damage. It is essential to control hyperlipidemia in renal transplant recipients to prevent these events. Methods In our study, we determined lipid profiles in 59 renal transplant recipients. Twenty of the recipients had hyperlipidemia; 9 had type IV, and 11 had type II hyperlipoproteinemia. Randomly selected 14 of 20 hyperlipidemic patients consisted of the diet group and were treated with American phase 3 diet for 1 month. Randomly selected 6 of the 20 hyperlipidemic patients received their regular diet as the control group. Five diet-resistant patients in the American phase 3 diet group were given diet plus placebo for another 1 month and then they were given diet plus Gemfibrozil (600 mg twice a day) for 2 months. Results Lipid profile was normalized in 9 of the 14 patients on American phase 3 diet. The lipid profile of 5 patients in the American phase 3 diet group did not change significantly after 1-month diet. These 5 diet-resistant patients were given diet plus placebo for another 1 month, and their lipid levels again did not change significantly. Afterward, they were treated with Gemfibrozil (600 mg twice a day) plus American phase 3 diet for 2 months. At the end of this therapy period, their cholesterol level and triglyceride level decreased significantly. No change was observed in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels. Conclusions We conclude that American phase 3 diet and/or Gemfibrozil are effective in controlling posttransplant hyperlipidemia in renal transplant recipients.
Association of Transforming Growth Factor β1 Gene Polymorphisms and Asbestos-Induced Fibrosis and Tumors
Authors: Helmig Simone , Belwe Alexandra , Schneider Joachim 
Published: May 2016

Aim Inhaled asbestos fibers are known to cause progressive lung or pleural fibrosis and malignancies such as lung cancer or diffuse malignant mesothelioma. Transforming growth factor β1 (TGF-β1), a multifunctional cytokine, regulates the proliferation and differentiation of cells. Transforming growth factor β1 is known to promote the pathogenesis of lung fibrosis and acts as a tumor suppressor in normal cells. Two genetic polymorphisms in codons 10 (Leu10Pro) and 25 (Arg25Pro) of the TGF-β1 gene are suggested to be associated with a different TGF-β1 protein production. Therefore, we examined an association between the 2 TGF-β1 gene polymorphisms and asbestos-induced lung fibrosis and lung cancer. Methods Detection of the 2 polymorphisms was performed by rapid capillary polymerase chain reaction, with melting curve analysis, using fluorescence-labeled hybridization probes. To investigate the association between TGF-β1 gene polymorphisms in codons 10 and 25 and the susceptibility to asbestos-induced diseases, association studies were performed with healthy control subjects (n = 83), patients with pulmonary fibrosis (n = 591), and patients with bronchial carcinoma (n = 147). Results Compared with a healthy control group, odds ratio (OR) analysis revealed an inverse relationship for the proline allele at codon 10 or 25 with pulmonary fibrosis (higher risk) and lung cancer (lower risk). The proline allele at codon 10 or 25 is significantly associated with a higher risk for fibrotic lung diseases (ORcrude, 1.46; 95% confidence interval [CI], 1.01-2.11; P = 0.045 and ORadjusted, 1.76; 95% CI, 1.14-2.72; P = 0.011, respectively, for codon 10; OR, 2.13; 95% CI, 1.33-3.99; P = 0.019 and ORadjusted, 2.27; 95% CI, 1.14-4.52; P = 0.02, respectively, for codon 25) when compared with patients with lung cancer. A significant association for the proline allele is also revealed when comparing patients with asbestosis (ORcrude, 3.01; 95% CI, 1.44-6.29; P = 0.003 and ORadjusted, 3.72; 95% CI, 1.56-8.85; P = 0.011) with patients with asbestos-induced lung cancer. Conclusions In summary, the results confirm the hypothesis that TGF-β1 polymorphisms are associated with asbestos-induced fibrotic or malignant lung diseases in whites.
Hepatitis B Virus and Hepatitis C Virus Seroprevalence in the Elderly Living in Nursing Homes
Authors: Maral Isil , Dogruman-Al Funda , Bakar Coskun , Ilhan Mustafa Necmi , Yalinay-Cirak Meltem , Bumin Mehmet Ali 
Published: May 2016

Background Communal living situations such as nursing homes create a risk for the spread of hepatitis B virus and hepatitis C virus (HCV). The aim of this study was to determine the seroprevalence of hepatitis B virus and HCV in the elderly living in 2 nursing homes in Ankara, Turkey. Methods A total of 227 persons (mean age, 76.11 ± 8.55 years) participated in this cross-sectional study. All individuals were investigated seroprevalence for hepatitis B surface antigen (HBsAg), anti-HBs immunoglobulin G (IgG), anti-hepatitis B core IgG, and anti-HCV IgG. Results Positive seroprevalence was 11.9% for HBsAg, 48.0% for anti-HBs IgG, 25.1% for anti-hepatitis B core IgG, and 2.5% for anti-HCV IgG. Hepatitis B surface antigen positivity was 12.4% in males and 11.5% in females ( P > 0.05); and the seroprevalence was 10.4% for those living in nursing homes for 1 year or less and 13.0% for those living in nursing homes for more than 1 year ( P > 0.05). Conclusions The fact that nearly half of those living in nursing homes had not encountered hepatitis B infection or had not received hepatitis B vaccination indicates the need for administering hepatitis B vaccines in this group.
P-Selectin and P-Selectin Glycoprotein Ligand 1 Mediate Rolling of Activated CD8+ T Cells in Inflamed Colonic Venules
Authors: Asaduzzaman Muhammad , Mihaescu Andrada , Wang Yusheng , Sato Tohru , Thorlacius Henrik 
Published: May 2016

Background Activated T cells regulate inflammatory diseases in the intestinal tract; however, the adhesive mechanisms governing CD8+ T-cell recruitment in the colon are not known. Methods Herein, we used a graft-versus-host disease (GvHD) model to study CD8+ T-cell rolling and adhesion in the large intestine by use of intravital fluorescence microscopy. Graft-versus-host disease was induced by transferring 50 × 106 allogeneic donor splenocytes from BDF1, B6, H-2b mice to recipient BDF1, H-2bxd mice. After 8 days, rhodamine-labeled CD8+ T cells (4 × 106) from healthy and GvHD mice were injected into both healthy and GvHD recipient mice, and CD8+ T-cell-endothelium interactions were studied in the colon. Results Activated CD8+ T cells from GvHD mice expressed higher levels of P-selectin ligand and decreased levels of L-selectin. Immunoneutralization of P-selectin and P-selectin glycoprotein ligand 1 reduced CD8+ T-cell rolling and adhesion in inflamed colonic venules by more than 71%. Inhibition of E-selectin had no effect on GvHD-induced CD8+ T-cell-endothelium interactions. Conclusions We conclude that P-selectin and P-selectin glycoprotein ligand 1 are dominating molecules in supporting adhesive interactions of CD8+ T cells in inflamed colonic venules and may be useful targets to protect against pathological inflammation in the large bowel.
It Takes Two to Tango: Combined Amylin/Leptin Agonism as a Potential Approach to Obesity Drug Development
Authors: Chan Jean L. , Roth Jonathan D. , Weyer Christian 
Published: May 2016

The discovery of leptin in 1994 was a seminal event in obesity research. It helped to establish that body weight is tightly regulated by a complex neurohormonal feedback system and that obesity should be viewed as a disorder with a strong biological basis rather than simply the result of poor lifestyle choices and lack of willpower. Leptin, secreted from adipocytes, acts as a prototypic long-term (tonic) adiposity signal. Although nonclinical and clinical studies have provided unequivocal evidence that leptin plays a unique, pivotal role in body weight regulation, efforts to develop recombinant leptin (metreleptin) as a monotherapy for obesity have proven unsuccessful. Amylin, secreted from pancreatic β-cells, fulfills the criteria for a short-term (episodic) satiety signal. The amylin analog pramlintide elicits sustained reductions in food intake and body weight in obese rodents and humans. A translational research program aimed at elucidating the interaction between different islet-, gut-, and adipocyte-derived hormones led to the discovery that combined amylin/leptin agonism induces marked, synergistic, fat-specific weight loss in leptin-resistant diet-induced obese rodents. In obese humans, combination treatment with pramlintide/metreleptin led to an approximately 13% weight loss after 24 weeks, significantly more than after treatment with pramlintide or metreleptin alone. Collectively, these findings suggest that combined amylin/leptin agonism may have therapeutic utility as part of an integrated, neurohormonal approach to obesity pharmacotherapy.
Association between T102C Polymorphism of Serotonin 2A Receptor Gene and Urinary Incontinence in Older Women
Authors: Noronha Jorge Antônio Pastro , Schwanke Carla Helena Augustin , Machado Denise Cantarelli , Braga Rafael , Lubianca Jeremia Mistrello , Sesti Fabiane Lorenzoni , de Toledo Aloysio Floriano , da Cruz Ivana Beatrice Mânica 
Published: May 2016

Background The bladder's regulatory function is influenced by central serotonergic modulation. T102C polymorphism of the serotonin 2A (5-HT2A) receptor gene is associated with urinary incontinence (UI) that has been reported by older community dwellers. We analyzed the association between 5-HT2A receptor gene polymorphism and urodynamic tests for UI in older women. Methods A case-control study was performed with 68 older women submitted to urodynamic evaluation and 162 older women without urinary problems (self-reported), all community dwellers enrolled in the Gravataí-GENESIS Project, Brazil. Clinical interviews, complete urodynamic evaluation following the International Continence Society Report on Good Urodynamic Practice (case group), and molecular analyses were performed (case and control groups). Serotonin 2A receptor gene genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme HpaII. We excluded patients with diabetes mellitus, neurologic damage, and diuretic intake. Results The subjects' mean (SD) age was 68.1 (6.5) years (range, 60-92 years). We found an association between the TT genotype versus CC + CT genotypes and UI ( P = 0.013; odds ratio, 2.69; 95% confidence interval, 1.37-5.29) and, in addition, an association with urgency UI, maximal cystometric capacity (TT, 349 mL; CC + CT, 429.5 mL [ P = 0.047]), detrusor pressure at maximum cystometric capacity (TT, 11 cm H2O; CC + CT, 6.75 cm H2O [ P = 0.032]), and detrusor compliance (TT, 34 mL/cm H2O; CC + CT, 61.25 mL/cm H2O [ P = 0.006]). Conclusions We confirmed our previous findings of a genetic influence of the TT genotype on UI involving the serotonergic pathway among older women. Further investigations including 5-HT2A expression in the bladder, pelvic floor, and striated sphincter muscle must be performed.