bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Resistin Level and Renal Function in Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Gungor Hasan , Kirilmaz Bahadir , Zorlu Ali , Oguz Emrah , Ayik Mehmet Fatih , Kumak Ferhat , Zoghi Mehdi
Published: May 2016

Aim

The purpose of this study was to evaluate the association between resistin levels and renal function in patients undergoing coronary artery bypass graft (CABG) surgery.

Methods

Thirty-seven consecutive patients (mean ± SD, age 60 ± 10 years, 29 (78%) male) undergoing CABG surgery at our department were enrolled into our study. Blood samples were taken to examine quantities of resistin level and other blood parameters the day before surgery. The patients were categorized into 2 groups: lower resistin level (group 1) or higher resistin level (group 2) according to the median value of 9 ng/mL.

Results

Mean ± SD resistin level, glomerular filtration rate (GFR), and urea and creatinine levels were 9.5 ± 4.2 ng/mL, 78 ± 25 mL/min per 1.73 m2, 42 ± 14 mg/dL, and 1.08 ± 0.2 mg/dL, respectively. Resistin showed significant correlation with serum levels of urea ( r = 0.448l P = 0.005), creatinine ( r = 0.367; P = 0.026), inverse correlation with GFR ( r = −0.398; P = 0.015), statin usage ( r = −0.393; P = 0.016), and β-blocker usage ( r = −0.365; P = 0.026). In the multivariate logistic regression model, only GFR (odds ratio, 0.960; 95 confidence interval, 0.928-0.993; P = 0.018) remained independently associated with higher resistin levels after adjustment of other potential confounders in patients undergoing CABG surgery. According to the receiver operating characteristics curve analysis, the optimal cutoff value of GFR to predict higher resistin levels was found as 91 mL/min or less per 1.73 m2, with 100% sensitivity and 61.1% specificity.

Conclusion

The present study demonstrated that a lower glomerular filtration rate was associated with higher circulating resistin levels, independent of coronary heart disease risk factors in patients undergoing CABG surgery.
Diagnostic Performance of Hemoglobin A1c for Prediabetes and Association with Cardiometabolic Risk Factors in Chinese Adolescents without Diabetes
Authors: Li Ping , Jiang Ranhua , Li Ling , Li Liang , Wang Zinan , Li Xue , Liu Cong
Published: May 2016

Aims

To examine the performance of hemoglobin A1c (HbA1c) in diagnosing prediabetes and whether it was associated with cardiometabolic risk factors in Chinese adolescents without known diabetes.

Methods

This was a cross-sectional study including 933 adolescents (aged 11-16 years; 46.5% girls) with HbA1c of 6.4% or less and fasting plasma glucose (FPG) of 6.9 mmol/L or less. All participants underwent anthropometric and biochemical examinations. The individuals with an increased HbA1c (5.7%–6.4%) were given a 75-g oral glucose tolerance test (OGTT).

Results

Of 213 subjects with an increased HbA1c or increased FPG (5.6–6.9 mmol/L), only 4.7% (n = 10) met both criteria. Among the 68 students with increased HbA1c who agreed to undergo the OGTT, only 18 subjects (26.5%) were confirmed to be prediabetic, and the receiver operating characteristic curve for HbA1c to identify prediabetes diagnosed by OGTT had an AUC of 0.53, which was not statistically significant ( P = 0.69). The waist circumference, FPG, uric acid, and homeostasis assessment model of insulin resistance were correlated with HbA1c (all P < 0.05). Hemoglobin A1c showed significant association with abdominal obesity and dyslipidemia and the clustering of cardiometabolic risk factors (odds ratios, 1.58–1.90; all P < 0.05). The cutoff point of HbA1c was 5.6% with a maximum accuracy in determining multiple cardiometabolic risk factors (sensitivity, 35.1%; specificity, 72.2%).

Conclusions

There is poor agreement between HbA1c and FPG or OGTT in diagnosing prediabetes, but the former was associated with the presence of multiple cardiometabolic risk factors in Chinese adolescents.
Different Antidiabetic Regimens and the Development of Renal Dysfunction in US Veterans with Type 2 Diabetes Mellitus
Authors: Gosmanova Elvira O. , Canada Robert B. , Wan Jim , Mangold Therese A. , Wall Barry M.
Published: May 2016

Aim

The aim of this study was to evaluate the development of renal dysfunction in veterans with type 2 diabetes mellitus (T2DM) treated with different antidiabetic regimens.

Methods

A retrospective cohort study involving 1715 patients with T2DM and baseline serum creatinine (SCr) of 1.5 mg/dL or lesser. The development of renal dysfunction, defined as 0.5 mg/dL or greater increase from baseline SCr during 4.8 years of follow-up with monotherapy metformin (M), 2 combination therapy groups: metformin + insulin (MI) and metformin + sulfonylurea (MS) users were compared with changes observed in sulfonylurea monotherapy users (S).

Results

Both MI and MS groups had higher mean baseline hemoglobin A1C (HbA1C) (9.0 and 8.6%, respectively) and higher rates of baseline macroalbuminuria (17.3 and 12.1%, respectively) as compared with M and S groups (mean HbA1C7.7% in both groups, and proteinuria M-5.1% and S-7.4%). In unadjusted analysis, the development of renal dysfunction was more frequent in MI and MS but not in M group as compared with sulfonylurea monotherapy (unadjusted HRs and [95% confidence interval (CI), 2.1[1.4–3.0], 1.4[1.1–1.9], and 1.0[0.6–1.7], respectively). However, differences in the development of renal dysfunction were not significant between the 4 groups after adjusting for baseline variables. Baseline macroalbuminuria was a strong predictor of Scr elevation of 0.5 mg/dL or greater during follow-up (adjusted HR, 3.1[1.9–4.7]). Unexpectedly, baseline use of renin-angiotensin-aldosterone system blockers was also associated with the development of renal dysfunction (adjusted HR, 1.9[1.3–2.8]).

Conclusions

In this retrospective cohort study involving US predominantly male veterans with T2DM, baseline macroalbuminuria and use of RAAS blockers were associated with increased risk of development of renal dysfunction, whereas different antidiabetic regimens were not.
Treatment of Malignant Gastric Outlet Obstruction with Metallic Stents
Authors: Cheng Hao-Tsai , Lee Ching-Song , Lin Cheng-Hui , Cheng Chi-Liang , Tang Jui-Hsiang , Tsou Yung-Kuan , Chang Jui-Min , Lee Mu-Hsien , Sung Kai-Feng , Liu Nai-Jen
Published: May 2016

Objectives

Gastric outlet obstruction (GOO) is a late complication of advanced gastric, pancreatic, and duodenal cancer. Palliative treatment of the obstruction is the main aim of therapy for these patients. Self-expandable metal stents are used for treating GOO. From our experience, the placement of the stent across the pylorus is easier and makes the curve of stent better than when the stent is placed within the duodenal area. The purposes of this study were to assess the efficacy of stents placed in either the duodenal area or across the pyloric valve in relieving GOO symptoms and to evaluate whether the location of the stent affects treatment outcomes.

Materials and Methods

This was a retrospective single-site study of 44 patients with malignant GOO. Expanding metal stents were placed either across the pyloric valve (n = 22; group A) or in the duodenum area (n = 22; group B). Improvement in oral intake was monitored using the Gastric Outlet Obstruction Scoring System (GOOSS). The end of the study was death of the last enrolled patient or 6 months after enrollment of the last patient, or whatever came first.

Results

Stent implantation similarly improved the patients’ tolerance for food intake from baseline for both groups A and B (median [interquartile range]; 2 [2–3] and 2 [2–3], respectively). Patients in group B who received adjunctive chemotherapy had greater improvement in GOOSS and survival than patients in group B who did not have chemotherapy or any group A patients ( P < 0.05). Stent patency was not affected by stent position or chemotherapy.

Conclusion

Palliative treatment of GOO with placement of an expandable metal stent improved the tolerability of food intake. The location of stent across the pyloric valve or within the duodenum did not affect the efficacy of the procedure or stent patency.
Insulin Resistance Predicts Steatosis and Fibrosis in Morbidly Obese Patients Undergoing Bariatric Surgery
Authors: Aller Rocio , de Luis Daniel , Pacheco David , Velasco Maria Concepcion , Izaola Olatz , Sagrado Manuel Gonzalez
Published: May 2016

Background

Influence of adipokines and insulin resistance on liver histology is an unclear area in morbidly obese patients.

Objective

The aim of our study was to study the influence of insulin resistance and adipokines in the grade of liver steatosis and fibrosis in morbidly obese patients undergoing bariatric surgery.

Setting

Tertiary hospital.

Materials and Methods

A sample of 36 morbidly obese patients undergoing bariatric surgery was analyzed in a cross-sectional study. A liver biopsy was performed. Weights, basal glucose, insulin, insulin resistance (homeostasis model assessment for insulin resistance [HOMA-IR]), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and adipokine blood levels were measured.

Results

Seventeen patients (47.2%) had low-grade steatosis, and 19 patients (52.8%) had high-grade steatosis. Sixteen patients (44.4%) did not have liver fibrosis, and 20 patients (56.6%) had liver fibrosis. Only insulin levels, HOMA-IR, and aspartate aminotransferase activity were higher in the patients with high-grade steatosis. Insulin levels and HOMA-IR were higher in patients with fibrosis. In the logistic regression analysis with a dependent dichotomous variable (grades of steatosis: low vs high), the HOMA-IR remained in the model, with an odds ratio to develop high-grade steatosis of 1.33 (95% confidence interval, 1.09–1.86). In the second logistic regression analysis with a dependent dichotomy variable (grades of fibrosis: present vs absent), the HOMA-IR remained in the model, with an odds ratio to develop fibrosis of 1.53 (95% confidence interval, 1.13–2.51).

Conclusion

Insulin resistance determined with HOMA-IR model is associated with high-grade steatosis and liver fibrosis in obese patients before bariatric surgery.
Long-Acting Beta 2 Agonists Suppress IP-10 Expression in Human Bronchial Epithelial Cells
Authors: Chien Jien-Wen , Chu Yu-Te , Yang San-Nan , Kuo Chang-Hung , Wang Wei-Li , Kuo Po-Lin , Jong Yuh-Jyh , Hung Chih-Hsing
Published: May 2016

Background

Interferon-γ-inducible protein (IP)-10 (CXCL10) is an important chemokine secreted by the airway epithelium that functions as a biomarker for virus-induced asthma. Long-acting beta 2 (β2) agonists (LABAs) are frequently used as inhaled medication for asthma and chronic obstructive pulmonary disease. However, previous research failed to investigate the effects of LABAs on IP-10 in bronchial epithelial cells.

Objective

To study the effects and signaling pathways of formoterol and salmeterol on polyriboinosinic polyribocytidylic acid (poly I:C)-induced IP-10 expression in BEAS-2B cells.

Methods

BEAS-2B cells were pretreated with formoterol and salmeterol for 2 hours before poly I:C stimulation. ICI 118551 (β2 adrenoreceptor antagonist) or mitogen-activated protein kinase (MAPK) inhibitors were added 30 minutes before LABAs were added. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were used to measure IP-10 protein and messenger RNA levels. Mitogen-activated protein kinase inhibitors and Western blotting were used to identify MAPK pathways, whereas bioassay revealed the MAPK functions.

Results

Long-acting β2 agonists significantly down-regulated the poly I:C-induced IP-10 protein and messenger RNA expression in BEAS-2B cells. ICI 118551 reversed this effect. Forskolin, a cyclic adenosine monophosphate activator, produced a similar inhibitory effect. Western blotting showed that formoterol suppressed poly I:C-induced IP-10 expression via the c-Jun N-terminal kinase–c-Jun pathway.

Conclusion

Long-acting β2 agonists down-regulate poly I:C-induced IP-10 expression in BEAS-2B cells via the β2 adrenoreceptor–cyclic adenosine monophosphate and c-Jun N-terminal kinase/c-Jun pathways. Long-acting β2 agonists also inhibit IP-10 production in bronchial epithelial cells and may prolong viral elimination.
Polymorphism G80A in the Reduced Folate Carrier Gene and its Relationship to Survival and Risk of Relapse in Acute Lymphoblastic Leukemia
Authors: Leyva-Vázquez Marco Antonio , Organista-Nava Jorge , Gómez-Gómez Yazmín , Contreras-Quiroz Adriana , Flores-Alfaro Eugenia , Illades-Aguiar Berenice
Published: May 2016

Background

The reduced folate carrier ( RFC1) is a major methotrexate transporter whose impaired function was recognized as a frequent mechanism of antifolate resistance. Recently, a G80A polymorphism has been described in the RFC1. This study evaluated the effect of the G80A polymorphism in the RFC1 gene on survival and risk of relapse of acute lymphoblastic leukemia.

Methods and Results

Seventy patients with acute lymphoblastic leukemia were genotyped by polymerase chain reaction restriction fragment length polymorphism method. An association between the polymorphism and risk of relapse was found ( P < 0.05). Patients with the G/A genotype have 3.97 (95% confidence interval, 1.12–14.06) and carriers of the A/A genotype have 7.84 (95% confidence interval, 1.66–37.10) higher chance of a relapse. Other variables such as age and leukocyte count were associated ( P < 0.05) with the risk of relapse of disease. Individuals with G/A or A/A genotypes had poorer survival (log-rank test, P = < 0.05).

Conclusions

These data suggest a role of the polymorphism G80A in the risk of relapse and the mortality risk in patients with acute lymphoblastic leukemia from the State of Guerrero, Mexico.
Early Elevation of Serum Tumor Necrosis Factor-α is Associated with Poor Outcome in Subarachnoid Hemorrhage
Authors: Chou Sherry H.-Y. , Feske Steven K. , Atherton Juli , Konigsberg Rachael G. , De Jager Philip L. , Du Rose , Ogilvy Christopher S. , Lo Eng H. , Ning MingMing
Published: May 2016

Objective

Subarachnoid hemorrhage (SAH) is associated with inflammation that may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) are associated with vasospasm and poor outcome in SAH.

Methods

In 52 consecutive SAH subjects, we compared TNF-α and IL-6 levels on post-SAH days 0 to 1, 2 to 3, 4 to 5, 6 to 8, and 10 to 14 with respect to vasospasm and to poor outcome at 3 and 6 months. Vasospasm was defined as more than 50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score greater than 2.

Results

Elevated TNF-α on post-SAH days 2 to 3 was associated with poor 3-month outcome ( P = 0.0004). Global elevation of TNF-α over time (post-SAH days 0–14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age ( P = 0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNF-α nor IL-6 levels were associated with vasospasm.

Conclusions

Elevation in serum TNF-α on post-SAH days 2 to 3 and global elevation of TNF-α over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNF-α in SAH-related brain injury and its potential as a SAH outcome biomarker.
Translational Research and the Evolving Landscape for Biomedical Innovation
Authors: Kaitin Kenneth I.
Published: May 2016

This article addresses current challenges facing pharmaceutical and biopharmaceutical developers, including the expiration of patents on many high-revenue–generating products, increasing competition in the marketplace, low public support, high regulatory hurdles, and the increasing time, cost, and risk of new product development. To meet these challenges, drug developers are looking to new models of innovation to improve efficiency, lower risk, and increase output. These new models include codevelopment agreements with small companies, multicompany consortia, and strategic partnerships with academic research centers. In the United States and the European Union, the government is supporting these efforts by creating incentives for academic centers to foster translational research and become more “commercially minded”. The goal for all stakeholders is to reduce the barriers to product development and bring new medicines to market in a timely and cost-efficient manner.
Combined Effects of Peroxisome Proliferator–Activated Receptor Alpha and Apolipoprotein E Polymorphisms on Risk of Breast Cancer in a Taiwanese Population
Authors: Wu Chen Teng , Cheng Ya-Hsin , Chen Fei-Na , Chen Dar-Ren , Wei Ming Feng , Chang Nai-Wen
Published: May 2016

Background

The peroxisome proliferator–activated receptor alpha (PPARA) and apolipoprotein E (APOE) proteins are reported to be correlated with lipid metabolism, cardiovascular disease, and breast cancer.

Methods

We screened APOE and PPARA ( S24F and V227A) polymorphisms in 306 breast cancer patients and 300 noncancer controls and determined the relationship between their genetic polymorphisms and breast cancer risk. Interactions with clinical characteristics were also examined.

Results

We found that the risk of breast cancer was associated with APOE genotypes ( P = 0.014) but not with PPARA S24F or V227A genotypes. The combined effects of F24/ APOE genotypes ( P = 0.003) on breast cancer risk were more significant than the individual effect of APOE genotypes ( P = 0.014). F24/ [Latin Small Letter Open E]4 carriers had a higher tendency to develop breast cancer than F24/ [Latin Small Letter Open E]3 carriers ( P = 0.013), and this effect is stronger than with individual [Latin Small Letter Open E]4 carriers ( P = 0.029). In addition, both F24/ [Latin Small Letter Open E]4 and V227/ [Latin Small Letter Open E]4 carriers were significantly enriched in the human epidermal growth factor receptor 2/neu negative status.

Conclusions

These findings suggest that the APOE [Latin Small Letter Open E]4 genotype plays a major role in the prediction of breast cancer, but the PPARA F24 mutation enhances this outcome. The combined effects of F24/ [Latin Small Letter Open E]4 genotypes are positively associated with risk of breast cancer.
Effect of Serum Gamma-Glutamyl Transferase Levels on Myocardial Perfusion and Long-Term Prognosis after Primary Angioplasty in Patients with Acute ST-Elevation Myocardial Infarction
Authors: Ozcan Firat , Karakas Mehmet Fatih , Ozlu Mehmet Fatih , Akcay Adnan Burak , Buyukkaya Eyup , Kurt Mustafa , Erden Gonul , Yuzgecer Huseyin , Yildirimkaya Metin , Hajro Edjon , Balbay Yucel , Koc Mevlut , Yazici Huseyin Ugur , Sen Nihat
Published: May 2016

Background

Gamma-glutamyl transferase (GGT) level was found to be elevated in plasma of patients with cardiovascular risk factors. The aim of our study was to assess the relationship between serum GGT levels and the occurrence of no-reflow as well as to evaluate the prognostic value of GGT in ST-segment elevation myocardial infarction (STEMI) population.

Methods and Results

One hundred sixty-eight consecutive patients with STEMI who underwent percutaneous coronary intervention (PCI) were enrolled in the study. Patients with STEMI were grouped into tertiles according to their admission serum GGT levels. No-reflow after PCI was assessed both angiographically (thrombolysis in myocardial infarction [TIMI] flow and myocardial blush grade) and electrocardiographically (ST resolution). Gamma-glutamyl transferase levels were higher in patients with STEMI compared to the elective PCI group subjects. Patients with angiographically (TIMI flow ≤2 or TIMI flow 3 with final myocardial bush grade ≤2 after PCI) and electrocardiographically (ST resolution <30%) detected no-reflow were increased in number across the GGT tertiles. In addition, 1-year mortality rates showed a significant increase across the tertile groups (4% vs 11% vs 23%, P < 0.01). Multivariable logistic regression analysis revealed that GGT levels on admission were a significant predictor of long-term mortality of myocardial blush grade–detected no-reflow phenomenon. High GGT level on admission was a significant predictor for long-term mortality and major adverse cardiac events.

Conclusions

In patients with STEMI undergoing primary PCI, high GGT levels at admission were found to be associated with no-reflow phenomenon and increased long-term mortality.
Effect of Fatty Acid–Binding Protein 2 Ala54Thr Genotype on Weight Loss and Cardiovascular Risk Factors after a High–Polyunsaturated Fat Diet in Obese Patients
Authors: de Luis Daniel , Aller Rocio , Izaola Olatz , Sagrado Manuel Gonzalez , de la Fuente Beatriz , Conde Rosa , Primo David
Published: May 2016

Background

It has been found that the expression of fatty acid-binding protein 2 messenger RNA is under dietary control. The aim of our study was to investigate the influence of Thr54 polymorphism in the FABP2 gene on weight loss and secondarily in cardiovascular risk factors and serum adipokine after an enriched polyunsaturated fat hypocaloric diet in obese patients.

Design

A sample of 111 obese patients was analyzed. The enriched polyunsaturated fat hypocaloric diet during 3 months’ intervention consisted of 1459 kcal, 45.7% carbohydrates, 34.4% lipids, and 19.9% proteins. The distribution of fats was as follows: 21.8% saturated fats, 55.5% monounsaturated fats, and 22.7% polyunsaturated fats. Level of significance was P < 0.05.

Results

In Ala54Ala genotype, body mass index (−1.6 ± 1.5 kg/m2), weight (−3.2 ± 3.3 kg), fat mass (−3.1 ± 3.5 kg), and waist circumference (−3.3 ± 2.1 cm) decreased. In carriers of the Thr54 allele, body mass index (−1.9 ± 1.6 kg/m2), weight (− 4.7 ± 1.4 kg), and waist circumference (−3.9 ± 3.7 cm) decreased. These changes were significantly higher in the carriers of the Thr54 allele than noncarriers. Only in the carriers of Thr54 allele, total cholesterol levels (−11.4 ± 20.6 mg/dl), low-density lipoprotein cholesterol levels (−5.4 ± 10.6 mg/dL), insulin (−2.6 ± 3.4 MUI/L), and the level of homeostasis model assessment for insulin sensitivity (−0.9 ± 1.7 U) decreased.

Conclusion

Carriers of Thr54 allele have a better metabolic response than obese carriers with Ala54Ala genotype, with a decrease of total cholesterol, low-density lipoprotein cholesterol, insulin levels, leptin levels, and homeostasis model assessment for insulin sensitivity.
How Does High-Fat Diet Induce Adipose Tissue Fibrosis?
Authors: Pessin Jeffrey E. , Kwon Hyokjoon
Published: May 2016

Obesity is one of the most serious pandemic health problems in modern society and the predisposing factor for the type 2 diabetes mellitus. Chronic low-grade inflammation mediates the pathogenesis of insulin resistance in obese humans and rodents, and white adipose tissue is one of major tissues to modulate inflammation. Obese humans and rodents show dynamic changes of immunocellular compositions in white adipose tissue to induce inflammatory responses. Innate and adaptive immune responses mainly mediated by macrophages and T cells contribute insulin resistance. Recently, it has been shown that adipose tissue fibrosis is also enhanced in obese humans and rodents along with inflammatory responses, and suppression of adipose tissue fibrosis shows improved insulin sensitivity in rodent models, suggesting that adipose tissue fibrosis is involved in insulin resistance.
Echocardiographic Evaluation of Asymptomatic Patients Affected by Rheumatoid Arthritis
Authors: Vizzardi Enrico , Cavazzana Ilaria , Bazzani Chiara , Pezzali Natalia , Ceribelli Angela , Bonadei Ivano , Franceschini Franco , D'Aloia Antonio , Metra Marco , Tincani Angela , Cas Livio Dei
Published: May 2016

Background

Rheumatoid arthritis (RA) is associated with increased mortality and morbidity because of accelerated atherosclerosis. The study assessed the prevalence of left and right ventricle diastolic and systolic dysfunction in outpatients with RA.

Methods

The study included 93 outpatients with RA. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted.

Results

In the group of RA patients, we found high prevalence of left ventricular systolic and diastolic dysfunction and right diastolic dysfunction compared with controls (13.5% vs 5.5 %, 76.3% vs 48.8% and 41.9% vs 6.6%, respectively; P < 0.001). Rheumatoid arthritis patients and controls showed significant differences about mitral, tricuspid, and pulmonary flow velocity curves; tissue Doppler curves of the lateral and the septal myocardial walls of the left ventricle; and basal myocardial free wall of the right ventricle. There were not any correlations between inflammatory and functional disease parameters and variables of systolic and diastolic function.

Conclusions

Our study shows a high prevalence of left ventricular systolic and diastolic dysfunction in a population of outpatients affected by rheumatoid arthritis.
Effect of Vitamin D Replacement on Insulin Sensitivity in Subjects with Vitamin D Deficiency
Authors: Simha Vinaya , Mahmood Muhammad , Ansari Mohammmed , Spellman Craig W. , Shah Pankaj
Published: May 2016

Background and Objective

Low vitamin D levels correlate with measures of insulin resistance and prevalence of diabetes mellitus, but there are limited and conflicting data on changes in insulin resistance after vitamin D replacement. The objective of the current study was to examine whether vitamin D replacement improves insulin sensitivity.

Methods

In this randomized double-blind placebo-controlled study, 12 healthy subjects with plasma 25-hydroxy vitamin D (25[OH]D) levels of less than 20 ng/mL were treated with ergocalciferol, 50,000 units, orally once a week for 8 weeks or matching placebo. The main outcome measure was insulin-stimulated glucose infusion rate during the last 20 minutes of a hyperinsulinemic-euglycemic glucose clamp study.

Results

At baseline, plasma 25(OH)D levels were similar between the ergocalciferol and placebo groups (13.3 ± 3.8 and 15.7 ± 2.4 ng/mL, respectively; P = 0.3) but were higher in the ergocalciferol group at 8 weeks (18.8 ± 5 vs 12.5 ± 2.2 ng/mL; P = 0.02). Glucose infusion rate was similar between the 2 groups both at baseline and after 8 weeks of treatment. Changes in plasma 25(OH)D levels did not correlate with change in glucose infusion rate.

Conclusion

Administration of ergocalciferol, 50,000 units, weekly for 8 weeks in subjects with low vitamin D levels improves 25(OH)D levels but does not improve insulin sensitivity.
Heart-Brain Signaling in Patent Foramen Ovale–Related Stroke
Authors: Lopez Mary F. , Sarracino David A. , Vogelsang Maryann , Sutton Jennifer N. , Athanas Michael , Krastins Bryan , Garces Alejandra , Prakash Amol , Peterman Scott , Demirjian Zareh , Inglessis-Azuaje Ignacio , Feeney Kathleen , Elia Mikaela , McMullin David , William Dec G. , Palacios Igor , Lo Eng H. , Buonanno Ferdinand , Ning MingMing
Published: May 2016

Patent foramen ovale (PFO) is highly prevalent and associated with more than 150,000 strokes per year. Traditionally, it is thought that PFOs facilitate strokes by allowing venous clots to travel directly to the brain. However, only a small portion of PFO stroke patients have a known tendency to form blood clots, and the optimal treatment for this multiorgan disease is unclear. Therefore, mapping the changes in systemic circulation of PFO-related stroke is crucial in understanding the pathophysiology to individualize the best clinical treatment for each patient. We initiated a study using a novel quantitative, 2-pass discovery workflow using high-resolution liquid chromatography–mass spectrometry/mass spectrometry coupled with label-free analysis to track protein expression in PFO patients before and after endovascular closure of the PFO. Using this approach, we were able to demonstrate quantitative differences in protein expression between both PFO-related and non–PFO-related ischemic stroke groups as well as before and after PFO closure. As an initial step in understanding the molecular landscape of PFO-related physiology, our methods have yielded biologically relevant information on the synergistic and functional redundancy of various cell-signaling molecules with respect to PFO circulatory physiology. The resulting protein expression patterns were related to canonical pathways including prothrombin activation, atherosclerosis signaling, acute-phase response, LXR/RXR activation, and coagulation system.

In particular, after PFO closure, numerous proteins demonstrated reduced expression in stroke-related canonical pathways such as acute inflammatory response and coagulation signaling. These findings demonstrate the feasibility and robustness of using a proteomic approach for biomarker discovery to help gauge therapeutic efficacy in stroke.
Coronary Disease Risk Curve of Serum Creatinine is Linear in Turkish Men, U-Shaped in Women
Authors: Onat Altan , Can Günay , Ademoğlu Evin , Çelik Etem , Karagöz Ahmet , Örnek Ender
Published: May 2016

Objectives

The highest levels of glomerular filtration rate are associated with increased coronary heart disease (CHD) risk, an issue we investigated in separate sexes in a population prone to metabolic syndrome.

Research Methods and Procedures

In total, 1948 participants of the Turkish Adult Risk Factor study with available creatinine determinations were studied at a mean 3.4 years’ follow-up. Using quartiles of creatinine, risk in Cox models of incident CHD or the likelihood of combined prevalent and incident CHD was assessed.

Results

Women in the lowest creatinine quartile demonstrated the lowest risk profile across diverse variables, except showing low high-density lipoprotein cholesterol and average apolipoprotein A-I and lipoprotein (a) concentrations implicating impaired atheroprotective properties. Whereas serum creatinine in men was not significantly associated with 6 proinflammatory variables comprised in linear regression analysis, apolipoprotein A-I and lipoprotein (a) were significant positive covariates in women, the latter tending to negative association in women without metabolic syndrome. In men, the highest (>1.10 mg/dL), compared with the lowest, creatinine quartile significantly predicted CHD risk, at 1.85-fold relative risks, after adjustment for established risk factors. The risk curve in women was U-shaped, the top and bottom quartiles tending to display higher risk (odds ratio, 1.28 [95% confidence interval, 0.91-1.80]) compared with the 2 intermediate quartiles.

Conclusions

Increasing serum creatinine values are associated strongly and independently with CHD risk in men but not in women in whom the risk curve is U-shaped. The phenomenon of low creatinine levels underlies some hitherto unexplained relevant observations, and low measurements may be attributed to inassayability secondary to involvement in autoimmune activation.
Type 1 Diabetes Treatment beyond Insulin: Role of GLP-1 Analogs
Authors: Harrison Lindsay B. , Mora Pablo F. , Clark Gregory O. , Lingvay Ildiko
Published: May 2016

Objective

To observe the efficacy and safety of glucagonlike peptide-1 (GLP-1) analogs in type 1 diabetes in a real-life medical practice setting.

Methods

We performed a retrospective chart review of patients with type 1 diabetes initiated on a GLP-1 analog and with at least one follow-up visit at more than 4 weeks.

Results

We identified 11 patients who were initiated on a GLP-1 analog and had a follow-up visit between 4 and 13 weeks (mean (SD) follow-up 10 ± 3 weeks; age 36.5 ± 16.4 years; duration of diabetes 17.3 ± 9.3 years; all on insulin pump therapy; all started on liraglutide). Seven of these patients had a second follow-up visit at approximately 20 weeks. By 10 weeks, there was a significant decrease in weight (4.2% of total body weight), total daily insulin dose (19.2%, of which 14.0% basal and 24.1% bolus), and mean (SD) insulin units/kg (0.57 [0.17] to 0.48 [0.17] units/kg). Hemoglobin A1c was significantly decreased (7.4 [0.7%] to 7.0 [0.7%], P = 0.02) without an increase in hypoglycemia. These effects were sustained at 20 weeks. Nausea was a common adverse effect and lead to drug discontinuation in 4 of 11 patients.

Conclusions

Patients with long-standing type 1 diabetes can achieve weight loss and improved glycemic control on less insulin without an increase in hypoglycemia when liraglutide is added to insulin therapy.
Acute Effects of Intracoronary Nitroglycerin and Diltiazem in Coronary Slow Flow Phenomenon
Authors: Ozdogru Ibrahim , Zencir Cemil , Dogan Ali , Orscelik Ozcan , Inanc Mehmet Tugrul , Celik Ahmet , Gur Mustafa , Elbasan Zafer , Kalay Nihat , Oguzhan Abdurrahman
Published: May 2016

Background

The coronary slow flow phenomenon (CSFP) is a coronary microvascular disorder angiographically defined by delayed opacification of the distal vasculature in the absence of obstructive coronary artery disease. We aimed to investigate and compare the effects of intracoronary nitrate and diltiazem on thrombolysis in myocardial infarction frame count (TFC) in patients with CSFP during coronary angiography.

Methods

Sixty patients with CSFP were randomly divided into 2 groups. The first group is nitroglycerin group with 30 patients (22 men; mean [SD] age, 50 [12] years), and the second is diltiazem group with 30 patients (27 men; mean age, 54 ± 11 years); intracoronary 5-mg diltiazem or 250-μg nitroglycerin was administered. Heart rate, systolic and diastolic blood pressures, and TFCs in all 3 coronaries were recorded before and after administering these medications.

Results

After nitroglycerin administration, systolic and diastolic blood pressures decreased, heart rates significantly increased, and TFCs decreased in all coronaries ( P < 0.001 for 3 coronaries). After the application of intracoronary 5-mg diltiazem, heart rate, systolic and diastolic blood pressures, and TFCs were found significantly lower than predrug values ( P < 0.001 for all values). When the percent TFC reductions, after the application of intracoronary diltiazem or nitroglycerin, in left anterior descending coronary artery, circumflex coronary artery, and right coronary artery were evaluated, diltiazem significantly reduced the TFCs of the left anterior descending coronary artery and circumflex coronary artery compared with nitroglycerin ( P < 0.01 for both coronaries).

Conclusion

Both intracoronary diltiazem and nitroglycerin improve the TFCs in CSFP, and intracoronary diltiazem is superior to nitroglycerin in reducing TFCs in CSFP.
Association Analysis between -308G/A and -238G/A TNF-Alpha Gene Promoter Polymorphisms and Insulin Resistance in Mexican Women with Gestational Diabetes Mellitus
Authors: Guzmán-Flores Juan Manuel , Escalante Miguel , Sánchez-Corona José , García-Zapién Alejandra Guadalupe , Cruz-Quevedo Edhit Guadalupe , Muñoz-Valle José Francisco , Moran-Moguel María Cristina , Saldaña-Cruz Ana Miriam , Flores-Martínez Silvia Esperanza
Published: May 2016

Background

Gestational diabetes mellitus (GDM) is characterized by insulin resistance. It has been described that tumor necrosis factor α (TNF-α) plays a key role in the pathogenesis of insulin resistance; moreover, increased levels of this proinflammatory cytokine have been reported in women with GDM. Therefore, this study was aimed to assess the presence of associations between the -308G/A and -238G/A polymorphisms and specific haplotypes of the TNF-α gene promoter region and insulin resistance in Mexican women with GDM.

Methods

This study included 51 women with GDM and 44 pregnant women with normal glucose tolerance. Measurements of anthropometric parameters and biochemical estimations were performed. We genotyped the TNF-α -308G/A and -238G/A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism analysis.

Results

The genotype and allele frequencies of both polymorphisms did not differ significantly between the women with GDM and the controls. However, we found that the frequency of the AG haplotype was significantly increased in the patients with GDM compared with controls ( P = 0.019; odds ratio, 4.11; 95% confidence interval, 1.31-12.85). In patients with GDM, we observed that insulin levels and homeostasis model assessment of insulin resistance were significantly higher in women bearing the G/G genotype than in carriers of the G/A and A/A genotypes of the -308G/A polymorphism ( P = 0.022 and P = 0.043, respectively).

Conclusions

Our results suggest that the G/G genotype of the TNF-α -308G/A polymorphism increases insulin levels and insulin resistance in women with GDM and that the AG haplotype is a genetic risk factor for GDM in our study population.
Activation of Carbohydrate Response Element-Binding Protein by Ethanol
Authors: Liangpunsakul Suthat , Ross Ruth A. , Crabb David W.
Published: May 2016

Objective

Carbohydrate response element-binding protein (ChREBP) is a transcription factor involved in hepatic lipogenesis. Its function is in part under the control of AMP-activated protein kinase (AMPK) and protein phosphatase 2A (PP2A). Given known effects of ethanol on AMPK and PP2A, it is plausible that ethanol might enhance fatty acid synthesis by increasing the activity of ChREBP. We hypothesized that another potential pathway of ethanol-induced hepatic steatosis is mediated by activation of ChREBP.

Methods

The effects of ethanol on ChREBP were assessed in hepatoma cells and in C57BL/6J mice fed with the Lieber-DeCarli diet.

Results

When the cells were exposed to ethanol (50 mM) for 24 hours, the activity of a liver pyruvate kinase (LPK) promoter-luciferase reporter was increased by ∼4-fold. Ethanol feeding of mice resulted in the translocation of ChREBP from cytosol to the nucleus. Protein phosphatase 2A activity was increased in the liver of ethanol-fed mice by 22%. We found no difference in the levels of hepatic Xu-5-P between ethanol-fed mice and controls. Transfection of a constitutively active AMPK expression plasmid suppressed the basal activity of the LPK luciferase reporter and abolished the effect of ethanol on the reporter activity. However, transfection of rat hepatoma cells with a dominant-negative AMPK expression plasmid induced basal LPK luciferase activity by only ∼20%. The effect of ethanol on ChREBP was attenuated in the presence of okadaic acid, an inhibitor of PP2A.

Conclusions

The effects of ethanol on AMPK and PP2A may result in activation of ChREBP, providing another potential mechanism for ethanol-induced hepatic steatosis. However, additional okadaic acid-insensitive effects appear to be important as well.
Lys656Asn Polymorphism of Leptin Receptor Gene is Related with Leptin Changes after a High Monounsaturated Fat Diet in Obese Patients
Authors: de Luis Daniel A. , Aller Rocio , Izaola Olatz , Conde Rosa , Eiros Bouza Jose
Published: May 2016

Background

Human obesity is characterized by high levels of leptin, and it has been suggested that obese patients may be leptin resistant. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on metabolic response, weight loss, and serum leptin levels to a high monounsaturated fat hypocaloric diet in obese patients.

Design

A sample of 126 obese patients was analyzed in a prospective way. The hypocaloric diet had 1342 kcal, 46.6% of carbohydrates, 34.1% of lipids, and 19.2% of proteins, with a 67.5% of monounsaturated fats, during 3 months.

Results

In Lys656Lys genotype, body mass index (−1.8 ± 1.4 kg/m2), weight (−4.3 ± 3.7 kg), fat mass (−3.5 ± 3.5 kg), waist circumference (−5.0 ± 2.9 cm), systolic blood pressure (−3.8 ± 10.5 mm Hg), insulin (−1.5 ± 4.6 mUI/L), and homeostasis model assessment of insulin resistance (−0.4 ± 1.9 Units) decreased. In Asn allele carriers, body mass index (1.5 ± 2.1 kg/m2), weight (−3.7 ± 3.1 kg), waist circumference (−4.4 ± 3.1 cm) decreased. Only leptin levels have a significant decrease in the Lys656Lys group (−6.9 ± 10.1 ng/mL) (24.2%).

Conclusions

Patients with Asn656 allele have a different response than Lys656Lys genotype subjects, with a lack of decrease in insulin levels, leptin levels, and homeostasis model assessment of insulin resistance after weight loss.
Association of MEFV Gene Mutations with Rheumatoid Factor Levels in Patients with Rheumatoid Arthritis
Authors: Inanir Ahmet , Yigit Serbulent , Karakus Nevin , Tekin Saban , Rustemoglu Aydin
Published: May 2016

Purpose

Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting the joints. Arthritis disorders are associated with mutations of the Mediterranean fever ( MEFV) gene. This gene has already been identified as being responsible for familial Mediterranean fever. The aim of this study was to explore the frequency and clinical significance of MEFV gene mutations in a cohort of Turkish patients with RA.

Methods

The study included 101 patients with RA and 110 healthy controls. Genomic DNA was isolated and genotyped using polymerase chain reaction and restriction fragment length polymorphism for the 5 MEFV gene mutations (M694V, M680I, V726A, E148Q, and P369S).

Results

Carrier rates of MEFV gene mutations were 31 (30.7%) of 101 and 26 (23.6%) of 110 in the RA and healthy control groups, respectively ( P > 0.05; odds ratio, 1.4; 95% CI, 0.77–2.65). Whereas deformed joint count was relatively higher in the mutation carrier group than those of the noncarrier group, the rheumatoid factor levels were significantly higher in the carrier group of patients with RA ( P = 0.001).

Conclusions

The results of this study suggest that MEFV gene mutations are not positively associated with a predisposition to develop RA but might increase the severity of RA. Further research is needed to determine the actual pathogenic role of MEFV mutations in this disease.
Resistin and Leptin Levels in Acromegaly: Lack of Correlation with Echocardiographic Findings
Authors: Gurbulak Sabriye , Yaylali Güzin Fidan , Yerlikaya Emrah , Akin Fulya , Topsakal Senay , Tanriverdi Halil , Akdag Beyza , Aslan Ali Riza
Published: May 2016

Purpose

To find out how resistin and leptin levels were affected in patients with acromegaly and whether there is a relation between resistin levels and cardiac parameters. We also aimed to investigate whether resistin and leptin may be a link between insulin resistance and cardiac functions as well as these affected cardiac functions in the patients with acromegaly.

Methods

We included 30 subjects (15 men and 15 women) who had a diagnosis of acromegaly and 30 healthy (10 men and 20 women) subjects. Serum glucose, insulin, growth hormone, insulinlike growth factor 1 (IGF-1), resistin, and leptin levels were obtained, and insulin resistance of subjects were calculated. Echocardiographic studies of the subjects were performed.

Results

Resistin levels of the patients with acromegaly were found lower than controls. This difference was statistically significant ( P = 0.001). Leptin levels were lower in the patients with acromegaly than in the controls, but this difference was not statistically significant. Resistin and leptin levels were not correlated with growth hormone, IGF-1, and with insulin-like growth factor binding protein 3 levels. Homeostasis model assessment of insulin resistance was positively correlated with resistin levels. ( P = 0.03; r = 0.531) but not correlated with leptin levels. There was a positive correlation between body mass index and leptin levels in the patients with acromegaly ( P = 0.007; r = 0.482). Interventricular septum thickness, posterior wall thickness, left ventricle mass index, peak early mitral inflow velocity–peak late mitral inflow velocity ratio, deceleration time, ejection time, isovolumetric relaxation time, velocity propagation, and left ventricular end-systolic volume values were significantly greater in the patients with acromegaly. Leptin levels in the acromegalic patients were not correlated with any of them.

Conclusions

We found biventricular hypertrophy and impairment of diastolic and systolic function in the patients with acromegaly. We conclude that changes in resistin and leptin levels are unlikely to account for the insulin resistance of acromegaly. They do not also seem to be contributing factors of cardiovascular changes in patients with acromegaly.
Urinary Tubular Protein-Based Biomarkers in the Rodent Model of Cisplatin Nephrotoxicity: A Comparative Analysis of Serum Creatinine, Renal Histology, and Urinary KIM-1, NGAL, and NAG in the Initiation, Maintenance, and Recovery Phases of Acute Kidney Injury
Authors: Sinha Vikash , Vence Luis M. , Salahudeen Abdulla K.
Published: May 2016

Background

Several biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared.

Objective

To compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI.

Methods

Sprague-Dawley rats (300–350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed.

Results

A significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P < 0.05]. The renal histology scores for brush border loss and tubular necrosis were significantly higher at 12 and 24 hours, respectively, in the CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P < 0.05] and remained elevated through day 10. Both urine NAG and NGAL levels were significantly higher by day 2 in the CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P < 0.05]. Urinary NAG remained elevated for 6 days and NGAL for 3 days.

Conclusions

Our study suggests a temporal hierarchy in the ability of certain urinary protein-based biomarkers to detect AKI after a well-defined tubular injury. Comparative analyses of urinary biomarkers are warranted in clinical settings such as patients receiving CP to discern the time course and pattern of expression.
Heat Shock Protein 70 Gene Polymorphisms in Japanese Patients with Aspirin-Exacerbated Respiratory Disease
Authors: Kikuchi Kiyokazu , Abe Shyuzo , Kodaira Kazumi , Yukawa Tatsuo , Hozawa Soichiro , Mochizuki Hiroyuki , Kurosawa Motohiro
Published: May 2016

Background

Aspirin-exacerbated respiratory disease (AERD) is nonatopic asthma, and the role of heat shock protein (HSP) 70 in AERD remains unknown. We analyzed HSP70 gene polymorphisms in Japanese patients with AERD.

Methods

The single-nucleotide polymorphisms in HSPA1B-179C>T and 1267A>G gene were examined in patients with AERD and those with aspirin-tolerant asthma (ATA). All patients were in a stable condition.

Results

There were significant differences in total serum IgE levels, peripheral blood eosinophil count, and prevalence of atopy between AERD and ATA. The patients with AERD showed higher frequencies of the CT/TT genotype of the HSPA1B-179C>T than that of the CC genotype compared to ATA ( P < 0.001). They showed higher frequencies of the GG genotype of the HSPA1B1267A>G than that of the GA/AA genotype compared to ATA ( P < 0.001). These differences were irrespective of the sex for the genotypes analyzed. The frequency of HSPA1B-179C/1267A haplotype was significantly higher in AERD compared to ATA ( P < 0.001; odds ratio, 3.154; 95% confidence interval, 1.916-5.193). Among the clinical and hematological characteristics investigated, AERD showed a significant variance in peripheral blood eosinophil count according to the association of the 2 HSP70 gene polymorphisms ( P = 0.033), but not in ATA.

Conclusions

Our findings first suggest that the association between HSPA1B-179C>T and 1267A>G gene sequence variations might be implicated in the development of AERD.