bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Dantrolene on Ischemia-Reperfusion Injury in Animal Models: A Review of Outcomes in Heart, Brain, Liver, and Kidney
Authors: Boys Joshua A. , Toledo Alexander H. , Anaya-Prado Roberto , Lopez-Neblina Fernando , Toledo-Pereyra Luis H.
Published: May 2016

Background/Objectives

Ischemia-reperfusion (IR) is the restoration of blood flow to a tissue that was formerly deficient of blood flow. Tissue damage after IR is considered an IR injury (IRI). During IR, there is an increased level of cytosolic calcium ([Ca2+]i) due to the release of calcium from mitochondrial, sarcoendoplasmic reticulum, and nuclear organelles. Dantrolene sodium (dantrolene) is a 1-[[[5-(4-nitrophenol)-2-furanyl]methylene]amino]-2, 4-imidazolidinedione sodium salt with a nonspecific mechanism, inhibiting organelle release of Ca2+ into the cytosol. This work reviews the outcomes of administering dantrolene in brain, heart, liver, and kidney animal models of IRI.

Methods

An extensive PubMed, MEDLINE, and MEDLAR literature review during the last 30 years on the effect of dantrolene in IRI in animal models was analyzed to determine the clinical implications of this important study. Particular attention was given to dantrolene in heart, brain, liver, and kidney IRI.

Results

Heart: Nine studies of heart IRI were reviewed and include an in vivo dog model (n = 1), in vivo rabbit model (n = 1), isolated dog myocardial fibers (n = 1), and isolated rat hearts (n = 6). Four studies showed decreased infarct size and increased cardiac function after IRI. One in vivo rabbit study found no difference in infarct size or cardiac function after IRI versus controls. Dantrolene may be protective or inductive of post-IRI arrhythmias depending on preestablished myocyte cycling times. Brain: Nine studies of brain IRI were reviewed and include an in vivo dog model (n = 1), in vivo gerbil model (n = 2), and in vivo rat models (n = 6). Dantrolene shows protective decreases in apoptotic markers in 6 studies, but it shows no effect on the necrotic core and mixed effects on reduction of infarct volume. One study found increased mortality in the dantrolene group. Liver: One study of in vivo rat liver IRI found that dantrolene decreased liver function tests, tissue necrosis factor α, tissue necrosis, and increased interleukin 10. Kidney: One study of in vivo rat kidney IRI showed that dantrolene had no effect.

Conclusions

Dantrolene shows protective effects in animal models of heart, brain, and potentially liver IRI, reinforcing the importance of calcium homeostasis during IRI. Variations of dose, timing of administration, route of administration, and outcomes between studies make definitive conclusions difficult. The nonspecific mechanism of action of dantrolene may also account for the variation among studies. Lack of studies in the liver and kidney makes any consensus in these organs premature, and thus, emphasis for this review was put on studies of the heart and brain.
Apolipoprotein C-III Gene Polymorphism and Several Environmental Factors with Serum Lipid Levels in the Guangxi Hei Yi Zhuang and Han Populations
Authors: Yiyang Li , Ruixing Yin , Meng Li , Kela Li , Xingjiang Long , Lin Zhang , Wanying Liu , Shangling Pan , Dezhai Yang , Weixiong Lin
Published: May 2016

Background

Apolipoprotein (apo) C-III gene polymorphisms have been associated with increased plasma triglycerides (TGs) and coronary artery disease, but the results have not always been concordant among diverse populations. The present study was undertaken to detect the association of the apoC-III 3238C>G polymorphism and several environmental factors with serum lipid profiles in the Guangxi Hei Yi Zhuang and Han populations.

Methods

A total of 490 subjects of Hei Yi Zhuang and 540 participants of Han Chinese aged 15 to 89 years were randomly selected from our previous stratified randomized cluster samples. Genotyping of the apoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis and then confirmed by direct sequencing.

Results

There was no difference in the genotype and allele frequencies between the 2 ethnic groups ( P > 0.05), but G allele and GG genotype frequencies were higher in females than in males, or in high TG than in normal TG individuals in Hei Yi Zhuang ( P < 0.01); and in high total cholesterol than in normal total cholesterol subgroups, in high low-density lipoprotein cholesterol (LDL-C) than in normal LDL-C subgroups, or in high apoB than in normal apoB subgroups in Han ( P < 0.05). There were also differences in the genotypic frequencies between normal apoA-I and low apoA-I subjects in Hei Yi Zhuang, and between males and females or between normal TG and high TG subgroups in Han ( P < 0.05). Serum TG and apoA-I levels were correlated with genotype or allele in Hei Yi Zhuang, and TG, LDL-C, and apoB levels were associated with genotype in Han ( P < 0.05). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index.

Conclusions

There were no significant differences in genotypic and allelic frequencies between the Hei Yi Zhuang and Han populations. But the 3238G carriers have unfavorable serum lipid profiles. The differences in the serum lipid profiles between the 2 ethnic groups might result from different gene-environmental interactions.
New-Onset Diabetes after Renal Transplantation
Authors: Mora Pablo F.
Published: May 2016

Transplantation medicine has grown to be an important element of medical practice, and with the development of modern immunosuppression agents and protocols, the occurrence of diabetes as renal transplantation is recognized as one of the metabolic consequences of therapy with these agents.

New-onset diabetes after transplantation can be defined as diabetes mellitus developing in any patient without history of diabetes before transplantation, who has sustained hyperglycemia that meets the current diagnostic criteria by the American Diabetes Association or by the World Health Organization.

New-onset diabetes after transplantation has been associated with the following risk factors: age, non-white ethnicity, hepatitis C infection, glucocorticoid therapy for rejection, and chronic immunosuppression with cyclosporine and tacrolimus. The observation that current immunosuppression using tacrolimus is one of the most important single risk factor for the development of new-onset diabetes after transplantation has been made.

The pathophysiology of this condition resembles that of type 2 diabetes mellitus. There is conclusive evidence that pretransplantation end-stage renal disease is an insulin-resistant state, and after transplantation, glucocorticoids induce further peripheral insulin insensitivity. The “second hit” seems to be an acquired (yet reversible) insulin secretion defect caused by the calcineurin inhibitors cyclosporine but more pronounced with tacrolimus. Future directions include pretransplantation and posttransplantation testing using glucose measurements and other techniques to identify high-risk individuals and possibly develop treatment strategies aimed to modify insulin resistance as well as to preserve beta cell function.
Carotid Intima-Media Thickness and Stiffness are Independent Risk Factors for Atherosclerotic Diseases
Authors: Tu Shih-Te , Wang I-Wen , Lin Hsiu-Fen , Liao Yi-Chu , Lin Ruey-Tay , Liu Chin-San , Juo SHH
Published: May 2016

Objective

We assessed the correlation between intima-media thickness (IMT) and stiffness and test whether they are independent risk factors for atherosclerotic diseases.

Methods

We enrolled 2333 participants from the general population. Among the study subjects, 197 subjects had a history of stroke or myocardial infarction (MI) and were treated as patients, and the rest were the control subjects. Intima-media thickness was measured at the common carotid artery (CCA), bifurcation, and internal carotid artery. Three parameters (arterial stiffness [β], elastic modulus, and pulse wave velocity) were measured for carotid stiffness. Correlation between IMT and stiffness was first calculated. Multivariate regression model was used to evaluate whether inclusion of both IMT and stiffness can increase the prediction of cardiovascular events.

Results

Only CCA and bifurcation IMTs were significantly and positively correlated with stiffness. After adjusting for age and sex, the correlations were substantially attenuated. Common carotid artery IMT was most significantly associated with stroke and MI ( P = 2.6 × 10−8) followed by bifurcation IMT ( P = 5.5 × 10−6), and internal carotid artery IMT was least significant ( P = 0.02). For stiffness, β was most significant ( P = 3.6 × 10−8) for stroke and MI, followed by elastic modulus ( P = 1.1 × 10−6) and pulse wave velocity ( P = 6.8 × 10−6). The best model for the combined effect was from β ( P < 0.03) and CCA ( P = 0.056) or bifurcation IMT ( P = 0.057).

Conclusions

Carotid IMT and stiffness represent different properties of atherosclerotic vessel wall. Measuring both traits provides a better characterization of atherosclerosis.
The Highs and Lows of Maternal Depression: Cluster Analysis of Depression Symptoms in a Sample of African American Women
Authors: Ronzio Cynthia R. , Mitchell Stephanie J.
Published: May 2016

Background

Maternal depression affects between 10% and 15% of US mothers. Emerging evidence suggests that variability in symptoms is linked to different risk factors and different pathological subtypes. Building on this research, this study examines manifestations of depression symptoms and risk factors associated with different manifestations among a socioeconomically heterogeneous sample of African American mothers.

Methods

Data were collected via telephone interviews with a community sample of 208 self-identified African American women with children 2 to 18 months old. Mothers were screened for depression symptoms using the Center for Epidemiological Studies Depression scale and reported on several psychosocial factors including social support, history of depression, and demographic characteristics. Cluster analysis was used to determine whether there were distinct subtypes of depression symptoms in this sample.

Results

A k-means cluster analysis of the 57 women with a positive depression symptom screen revealed 2 distinct groups characterized by higher versus lower symptom severity. A logistic regression indicated that mothers were more likely to fall into the high severity cluster if they were employed and reported lower levels of social support.

Limitations

Because of its cross-sectional design, this study could not explore the timing and the course of depression symptoms, which may be more closely related to risk and functional impairment than the severity distinction found in this research.

Conclusions

Researchers, pediatricians, and obstetricians working with African American mothers should screen for social support, with the understanding that those with low levels may be at increased risk for severe depression symptoms. Finally, the heterogeneity in symptoms suggests that clinicians should be aware of all depression symptoms among their patients rather than looking for specific, potentially stereotypical symptoms as cues.
Infliximab Reduces the Frequency of Interleukin 17-Producing Cells and the Amounts of Interleukin 17 in Patients with Rheumatoid Arthritis
Authors: Shen Hui , Xia Liping , Lu Jing , Xiao Weiguo
Published: May 2016

Background

To detect frequency changes in interleukin 17 (IL-17)+ CD4+ T cells and the amounts of IL-17 in supernatants between baseline and 30 weeks after Infliximab combined with methotrexate (MTX) or MTX-alone therapy.

Methods

Flow cytometry was used to analyze the frequency of IL-17+ CD4+ T cells in rheumatoid arthritis (RA) patients and control subjects at baseline and 30 weeks after therapy. Secretion of IL-17 by peripheral blood mononuclear cells was measured by enzyme-linked immunosorbent assay.

Results

The percentages of IL-17+ CD4+T cells were increased in the peripheral blood mononuclear cells of patients with RA compared with healthy subjects. The percentages of IL-17+ CD4+T cells were correlated with the number of swelling joints and C-reactive protein of RA patients. Likewise, concentrations of IL-17 in supernatants from patients with RA were significantly higher compared with those from control subjects. After infliximab combined with MTX or MTX-alone therapy, the number of swelling joints, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and Disease Activity Score 28 decreased significantly compared with baseline. Only in the infliximab + MTX group that the frequency of TH17 cells and concentration of IL-17 decreased.

Conclusions

These data support the hypothesis that infliximab therapy can have an effect on TH17 cells and decrease disease activity.
Design of a Bioartificial Pancreas
Authors: Opara Emmanuel C. , Mirmalek-Sani Sayed-Hadi , Khanna Omaditya , Moya Monica L. , Brey Eric M.
Published: May 2016

Introduction

In type 1 diabetes, the β-cells that secrete insulin have been destroyed such that daily exogenous insulin administration is required for the control of blood glucose in individuals with the disease. After the development of reliable techniques for the isolation of islets from the human pancreas, islet transplantation has emerged as a therapeutic option, albeit for only a few selected patients largely because there are not enough islets for the millions of patients requiring the treatment, and there is also the need to use immunosuppressive drugs to prevent transplant rejection. In 1980, the concept of islet immunoisolation by microencapsulation was introduced as a technique to overcome these 2 major barriers to islet transplantation. Microencapsulation of islets and transplantation in the peritoneal cavity was then described as a bioartificial pancreas. However, it is difficult to retrieve encapsulated islets transplanted in the peritoneal cavity, thus making it difficult to meet all the criteria for a bioartificial pancreas. A new design of a bioartificial pancreas comprising islets co-encapsulated with angiogenic protein in permselective multilayer alginate-poly-L-ornithine-alginate microcapsules and transplanted in an omentum pouch is described in this paper.

Materials and Methods

The multilayer alginate-poly-L-ornithine-alginate microcapsules are made with ultrapure alginate using poly-L-ornithine as a semipermeable membrane separating the 2 alginate layers. The inner alginate layer is used to encapsulate the islets, and the outer layer is used to encapsulate angiogenic protein, which would induce neovascularization around the graft within the omentum pouch.

Results

In in vitro studies, we found that both the wild-type and the heparin-binding growth-associated molecule (HBGAM)-fibroblast growth factor-1 chimera can be encapsulated and released in a controlled and sustained manner from the outer alginate layer with a mean diameter in the range of 113 to 164 µm when 1.25% high guluronic acid alginate is used to formulate this outer layer.

Discussion

We are currently performing in vivo experiments to determine the ability of angiogenic proteins released from this outer layer to induce neovascularization around the grafts in the omentum pouch. We will subsequently examine the effect of co-encapsulation of islets with angiogenic protein on blood glucose control in diabetic animals. It is hoped that addition of tissue engineering to encapsulated islet transplantation will result in long-term survival of the islets and their ability to control blood glucose in type 1 diabetes without the necessity to use risky immunosuppressive drugs to prevent transplant rejection.
Using a Type 1 Collagen-Based System to Understand Cell-Scaffold Interactions and to Deliver Chimeric Collagen-Binding Growth Factors for Vascular Tissue Engineering
Authors: Pang Yonggang , Greisler Howard P.
Published: May 2016

Vascular tissue engineering should provide more biocompatible and functional conduits than synthetic vascular grafts. Understanding cell-scaffold interactions and developing an efficient delivery system for growth factors and other biomolecules to control the signaling between the cells and the scaffold are fundamental issues in a wide range of tissue engineering research fields. Type 1 collagen is a natural scaffold extensively used in vascular tissue engineering and is a widely used vehicle in biomolecule delivery. In this article, we will discuss type 1 collagen as a vascular tissue engineering scaffold, describe strategies for elucidating the interaction between cells and type 1 collagen scaffolds using various imaging techniques, and summarize our work on the development of a chimeric collagen-binding growth factor-based local delivery system.
Airway Platelet Activation is Associated with Airway Eosinophilic Inflammation in Asthma
Authors: Benton Angela S. , Kumar Nikila , Lerner Jennifer , Wiles Andrew A. , Foerster Matthew , Teach Stephen J. , Freishtat Robert J.
Published: May 2016

Background

Allergic asthma is characterized by airway inflammation associated with recruitment and activation of eosinophils. In mice, allergen exposure induces platelet migration to the airways that is necessary for eosinophil recruitment and activation. We therefore hypothesized that in the airways of human subjects with asthma, platelet activation would be positively associated with eosinophil activation and platelet and eosinophil activation would both be associated with clinical asthma characteristics.

Methods

Nasal wash levels of P-selectin (a measure of platelet activation) and eosinophil cationic protein (ECP) (a measure of eosinophil activation) were compared with each other and with clinical asthma characteristics in a cross-sectional study of urban children and adolescents (age range, 6-20 years) with asthma.

Results

Regression analysis revealed a significantly positive association between log10 P-selectin levels and log10 ECP levels (β = 0.50 ng/mL [95% confidence interval, 0.05-0.94 ng/mL]; P = 0.029). Additionally, ECP was significantly and negatively associated with 2 asthma-related quality of life measurements, and P-selectin was associated with one of these.

Conclusions

Our study shows the first significant association between platelet and eosinophil activation in airways of human subjects with asthma. These data provide a first step toward delineating what seems to be an important role for platelets in airway eosinophilia.
MicroRNA-155 Silencing Enhances Inflammatory Response and Lipid Uptake in Oxidized Low-Density Lipoprotein-Stimulated Human THP-1 Macrophages
Authors: Huang Ri-sheng , Hu Guan-qiong , Lin Bin , Lin Zhi-yi , Sun Cheng-chao
Published: May 2016

It has been proposed that the inflammatory response of monocytes/macrophages induced by oxidized low-density lipoprotein (oxLDL) is a key event in the pathogenesis of atherosclerosis. MicroRNA-155 (miR-155) is an important regulator of the immune system and has been shown to be involved in acute inflammatory response. However, the function of miR-155 in oxLDL-stimulated inflammation and atherosclerosis remains unclear. Here, we show that the exposure of human THP-1 macrophages to oxLDL led to a marked up-regulation of miR-155 in a dose-dependent manner. Silencing of endogenous miR-155 in THP-1 cells using locked nucleic acid-modified antisense oligonucleotides significantly enhanced oxLDL-induced lipid uptake, up-regulated the expression of scavenger receptors (lectinlike oxidized LDL receptor-1, cluster of differentiation 36 [CD36], and CD68), and promoted the release of several cytokines including interleukin (IL)-6, -8, and tumor necrosis factor α (TNF-α). Luciferase reporter assay showed that targeting miR-155 promoted nuclear factor-kappa B (NF-κB) nuclear translocation and potentiated the NF-κB-driven transcription activity. Moreover, miR-155 knockdown resulted in a marked increase in the protein amount of myeloid differentiation primary response gene 88 (MyD88), an important adapter protein used by Toll-like receptors to activate the NF-κB pathway. Our data demonstrate that miR-155 serves as a negative feedback regulator in oxLDL-stimulated THP-1 inflammatory responses and lipid uptake and thus might have potential therapeutic implications in atherosclerosis.
Age, Sex, and Ethnicity May Modify the Influence of Obesity on Inflammation
Authors: Laurson Kelly R. , McCann Dustin A. , Senchina David S.
Published: May 2016

Objectives

Many medical concerns associated with obesity are due to chronic inflammation, but factors underlying the development or maintenance of obesity-associated inflammation remain unclear. This study investigated how age, sex, and ethnicity may modify the interplay of subclinical inflammation and obesity in nationally representative contexts.

Methods

Using National Health and Nutrition Examination Survey data from 1999 to 2008, we assessed the role of these demographic factors on immunological markers of subclinical inflammation (such as total white blood cell counts, white blood cell subpopulation counts, and C-reactive protein [CRP] levels) in both obese and nonobese individuals. Approximately 9756 individuals were included in the analysis after removing individuals with confounding conditions.

Results

The CRP levels, total white blood cell count, and white blood cell subpopulation counts increased with increasing body mass index (BMI). After controlling for BMI, female subjects had greater levels of most inflammatory markers compared with male subjects. After controlling for age, sex, and ethnicity, the following inflammatory markers significantly increased with increasing BMI: CRP and white blood cell, lymphocyte, monocyte, and neutrophil counts. Basophil and eosinophil counts also increased with increasing BMI but not significantly.

Conclusions

Factors, such as age, sex, and ethnicity, may modify the influence of obesity on subclinical inflammation at the population level.
Assessment of Atrial Conduction Time in Patients with Sarcoidosis
Authors: Buyukoglan Hakan , Kaya Mehmet Gungor , Ardic Idris , Yarlioglues Mikail , Dogdu Orhan , Bol Canan , Sahin Omer , Kanbay Asiye , Koç Fatih , Ozdogru Ibrahim
Published: May 2016

Objectives

Sarcoidosis is an inflammatory granulomatous disease of unknown cause that involves multiple organ systems. Myocardial involvement is usually associated with poor prognosis, but diagnosis of cardiac sarcoidosis is frequently difficult. The aim of this study was to investigate the atrial conduction time in patients with sarcoidosis by using high-usefulness tissue Doppler echocardiography.

Methods

The study population included 49 patients with sarcoidosis (19 men; mean age, 40.5 ± 9.8 years; mean disease duration, 35.7 ± 15.3 months) and 45 healthy control subjects (17 men; mean age, 40.7 ± 7.2 years). From the 12-lead electrocardiogram, P wave dispersion (PWD) was calculated. The timing of atrial contractions (PA) was measured as the intervals between the onset of P wave on electrocardiogram and the beginning of A-wave on TDI, and atrial electromechanical delay (EMD) was calculated from the lateral (PA lateral) and septal (PA septal) mitral annulus and lateral tricuspid annulus (PA tricuspid).

Results

Both PA lateral and PA septal were significantly longer in patients with sarcoidosis than control subjects (67.9 ± 16.1 vs 56.3 ± 13.1, P < 0.001; and 54.8 ± 15.2 vs 45.1 ± 14.2 ms, P = 0.002, respectively). Intra-atrial (PA septal-PA tricuspid) and interatrial (PA lateral-PA tricuspid) EMD were significantly higher in sarcoidosis groups (12.6 ± 7.5 vs 8.0 ± 7.1, P = 0.003; and 25.7 ± 9.8 vs 19.3 ± 7.7 ms, P = 0.001, respectively). Similarly, maximum P-wave duration and PWD were significantly longer in patients with sarcoidosis than control subjects (105.2 ± 11.8 vs 96.7 ± 15.4, P = 0.004 and 24.7 ± 5.6 vs 19.7 ± 7.1 ms, P = 0.001, respectively). There were significant positive correlations between the disease duration and interatrial EMD ( r = 0.56, P < 0.001) and intra-atrial EMD ( r = 0.66, P < 0.001). Positive correlation also was present between the disease duration and PWD ( r = .62, P < 0.001).

Conclusions

Atrial EMD was found prolonged in patients with sarcoidosis. We also have demonstrated that PWD, interatrial and intra-atrial EMD were significantly correlated with disease duration. This study calls attention to measurement of atrial conduction time that may be clinically helpful in the recognition of cardiac involvement.
Comparison of Characteristics and Outcomes of Patients Undergoing Saphenous Vein Graft Stenting who were or were not Enrolled in the Stenting of Saphenous Vein Grafts Randomized Controlled Trial
Authors: Michael Tesfaldet T. , Badhey Neeraj , Banerjee Subhash , Brilakis Emmanouil S.
Published: May 2016

Objective

We sought to compare the characteristics and outcomes of patients who were enrolled versus those who were not enrolled in the Stenting of Saphenous Vein Grafts (SOS) randomized controlled trial.

Methods and Results

We identified all patients who underwent saphenous vein graft stenting during the SOS Trial enrollment period (May 2005 and October 2007) at our institution. Baseline characteristics and clinical outcomes were compared between patients who were versus those who were not enrolled in SOS. Of the 97 patients who underwent saphenous vein graft stenting during the study period, 62 patients (64%) were enrolled in SOS. In the enrolled group, 62 patients with 91 lesions were randomized to a bare metal stent (BMS) (n = 39) or paclitaxel-eluting stent (n = 41). In the nonenrolled group, 35 patients with 44 lesions received a drug-eluting stent (DES) (n = 27) or BMS (n = 8). During a median follow-up period of 2.66 years, nonenrolled patients had higher mortality (31.4% vs 14.5%, P = 0.039), but lower rates of myocardial infarction (5.7% vs 32.3%, P = 0.005) and target vessel failure (37% vs 61.3%, P = 0.023). Overall, patients who received DES had lower incidence of myocardial infarction, target lesion revascularization, target vessel failure and major adverse cardiac events, and similar mortality compared with the BMS group.

Conclusions

Compared with nonenrolled patients, those who were enrolled in SOS had lower mortality. Patients receiving DES had better outcomes than those receiving BMS in both groups.
Telmisartan Improves Insulin Resistance in Patients with Low Cytokine Levels
Authors: Sanchez Muñoz-Torrero Juan Francisco , Rivas Maria D. , Costo Alberto , Crespo Leandro , Fraile Juana , Doncel Carlos , Fernandez Toro Jose Maria , Zamorano Jose
Published: May 2016

Metabolic syndrome (MS) is a disease with an inflammatory component. Telmisartan improves insulin resistance in MS, but its relationship with the inflammatory state is unknown. We investigated the effect of 3-month telmisartan therapy on homeostatic model assessment-insulin resistance (HOMA-IR) in hypertensive subjects with MS with regard to the levels of circulating plasma cytokines.

Methods

A total of 42 patients were included in this study; 30 were men (71%), aged 50 ± 8.2 years (mean ± SD). Cytokines and metabolic parameters were analyzed before and after treatment with telmisartan.

Results

Twenty-eight patients showed low plasma levels of cytokines (group 1) similar to control subjects, and 14 showed high levels (group 2). Treatment with telmisartan diminished by 35% HOMA-IR in group 1 (4.5 ± 3.1 vs 2.9 ± 2.1), without improvement in group 2. In the multivariate analysis, the predictors of improvement of HOMA-IR in response to telmisartan treatment were low levels of cytokines, whereas systolic and diastolic blood pressure and the elevation of high-sensitivity C-reactive protein had a negative effect.

Conclusions

Our study provides evidence of a more favorable effect of telmisartan on glucose homeostasis in patients with MS and low levels of serum cytokines.
Increased Platelet and Erythrocyte Arginase Activity in Chronic Obstructive Pulmonary Disease Associated with Tobacco or Wood Smoke Exposure
Authors: Guzmán-Grenfell Alberto , Nieto-Velázquez Nayeli , Torres-Ramos Yessica , Montoya-Estrada Araceli , Ramírez-Venegas Alejandra , Ochoa-Cautiño Leticia , Flores-Trujillo Fernando , Hicks Juan José
Published: May 2016

Background

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that is characterized by a progressive and irreversible decline in lung function and is caused primarily by chronic exposure to tobacco and to wood smoke. It is linked to oxidative stress and to an up-regulation of airway arginases and is also associated with alterations in platelets and erythrocytes. In the present study, arginase activity was studied in platelets and erythrocytes of 2 groups of COPD patients: 31 tobacco ex-smokers and 27 patients who had been exposed to wood smoke. A total of 15 healthy controls were also included.

Methods

Plasma, platelets, and erythrocytes were obtained from the blood samples. Levels of the oxidative stress biomarkers, carbonyls and malondialdehyde, were measured in the plasma, and arginase activity was quantified in platelets and erythrocytes.

Results

In both groups of COPD patients, an increase in the oxidative stress biomarkers was found. Platelet arginase activity in both COPD groups was 2-fold higher than that in the control group. In the erythrocytes, the arginase activity increased 1.7-fold over the control only in the wood smoke-induced COPD group.

Discussion and Conclusions

These results suggest that the increase in arginase activity in platelets and erythrocytes participates in the alteration in nitric oxide metabolism in COPD patients and that there may be some differences between the tobacco smoke- and wood smoke-induced COPD.
Relationship of the Protein Z Intron F G79A and IL6 C634G Gene Polymorphisms with the Risk of Recurrent Pregnancy Loss in Egyptian Women
Authors: El-Hamid Samah Abd , El-Khayat Waleed
Published: May 2016

Purpose

To investigate the relationship between recurrent pregnancy loss and single nucleotide polymorphisms in the protein Z (PZ) intron F G79A and the promoter region of the IL6 C634G genes in Egyptian women.

Procedures

Single nucleotide polymorphisms in the PZ intron F G79A gene and the promoter region of the IL6 C634G gene were studied in 70 Egyptian women; 40 patients and 30 healthy and parous volunteers using the polymerase chain reaction-restriction fragment length polymorphism technique.

Results

Regarding the PZ intron F G79A polymorphism; a higher prevalence of the A allele in the controls (53.3%) compared with the cases (22.5%) was found, and the difference proved to be statistically significant ( P = 0.008). As for the IL6 C634G polymorphism, the frequency of the G allele was higher in the controls (100%) than in the cases (95%), but the difference did not prove to be statistically significant ( P = 0.503). A statistically significant difference between the prevalence of the IL6 C634G (95%) and the PZ intron F G79A (22.5%) was detected ( P ≤ 0.001).

Conclusion

A statistically significant difference of the frequency of the A allele of the PZ intron F G79A polymorphism was found with a higher prevalence of the A allele among the controls compared with the patients, suggesting a lower risk of recurrent pregnancy loss among the studied patients, but the IL6 C634G polymorphism did not prove to have an equivalent effect.
Your Idea and Your University: Issues in Academic Technology Transfer
Authors: Smith Charles D.
Published: May 2016

Research discoveries may lead to products for commercial development. A central consideration for the researcher is how involved she or he will be in the commercialization process. In some cases, a university out-licenses the intellectual property, whereas in other cases, the investigator may want to be involved in the development process and choose to start his or her own company to develop and possibly to manufacture and sell the product. Before undertaking such a challenge, however, the investigator-turned-entrepreneur must consider a variety of issues, including career goals, financial and time commitments, potential conflicts of interest and/or commitment, start-up funding, and his or her ability to run a company or step aside to allow business experts to make necessary decisions. This paper discusses some personal considerations in deciding to start a spinout company and provides information on some of the available government grants to assist you should you decide to undertake your product's commercial development. In particular, the Small Business Innovative Research and Small Business Technology Transfer programs of federal funding agencies often are the source of early funding for new biomedical companies.
Effect of Hyperglycemia on Human Monocyte Activation
Authors: Nandy Debashis , Janardhanan Rajiv , Mukhopadhyay Debabrata , Basu Ananda
Published: May 2016

Our recent study defined the chemokine-induced human monocyte signaling under normoglycemic condition. To explore the hyperglycemia-induced monocyte signaling, we performed adhesion, migration, and transmigration assays on human monocytes obtained from THP-1 cell line in the presence of normal (5 mM) and high (10 and 20 mM) glucose concentrations without chemokines. We observed augmented ( P < 0.01) monocyte adhesion to human umbilical vein endothelial cell monolayer at 10 than 5 mM glucose with no further increase at 20-mM glucose concentration ( P < 0.07 vs 10 mM; P < 0.01 vs 5 mM). But incremental increases in monocyte migration ( P < 0.01), transmigration ( P < 0.01), and stress fiber response ( P < 0.01) were observed at 10- and 20-mM glucose concentrations in comparison to 5-mM glucose concentrations. We found gradational increase ( P < 0.01) in phosphorylation of Akt S473 and glycogen synthase kinase (GSK3βS9) in hyperglycemia (10 and 20 mM) when compared with 5 mM glucose. Furthermore, hyperglycemia (both 10 and 20 mM)-treated monocyte showed up-regulated phosphorylation of p101 and p110γ subunits of PI-3 kinase in comparison to 5 mM glucose. Hyperglycemia-induced monocyte migration was restored to basal levels in the presence of PI-3 kinase inhibitor, LY. These observations imply that modest hyperglycemia per se, as is commonly observed in diabetic individuals, is a potent stimulator of monocyte activity even without chemokines.
The Erythropoietin Receptor: Molecular Structure and Hematopoietic Signaling Pathways
Authors: Watowich Stephanie S.
Published: May 2016

The process of erythropoiesis in the fetal liver and adult bone marrow is regulated by the hormone erythropoietin (Epo), which is produced in the kidney at low levels under homeostatic conditions. Defects in Epo production result in severe anemia; use of recombinant hormone has improved the lives of patients with renal failure or anemia because of bone marrow suppression. Deletion of the Epo gene in mice leads to embryonic lethality at days 13 to 15, coincident with the establishment of definitive (adult-type) erythropoiesis and underscoring the absolute necessity of Epo function in vivo. Epo has proven to be a successful pharmaceutical agent, one of the early triumphs of recombinant protein technology. Because of its clinical importance, a great deal of attention has focused on the molecular mechanisms of Epo-regulated erythropoiesis. This review highlights the basic concepts of Epo signal transduction within the hematopoietic system, the major site of Epo action in vivo.
Intent to Update Systematic Reviews: Results of an Internet Survey
Authors: Phung Olivia J. , Baker William L. , Baker Erica L. , Coleman Craig I.
Published: May 2016

Background

Updating a systematic review may be necessary when newer evidence is available. Several barriers to conducting updated systematic reviews have been hypothesized.

Aims

To conduct an Internet survey to identify the relationship between author and study characteristics and the intent to update a systematic review, to quantify this relationship, and to query authors about perceived barriers to updating.

Methods

Manual search of ACP Journal Club (January 2007-December 2008) for featured systematic reviews and/or meta-analyses identified participants. We collected participant demographics and questioned participants on intentions of updating and potential barriers. All variables showing univariate association ( P < 0.1) were entered into a backward-stepwise multivariate model.

Results

Upon multivariate logistic regression, those who spend greater than 25% of time dedicated to systematic review were significantly more likely to update their review (adjusted odds ratio, 7.25; 95% confidence interval, 1.45-35.71). Conversely, those whose primary funding was from a government source were significantly less likely to conduct an update (adjusted odds ratio, 0.08; 95% confidence interval, 0.01-0.50).

Conclusions

Authors who spend more time on systematic reviews were more likely to update, whereas those with government funding were less likely to update their systematic reviews. Surveyed authors also identified several perceived barriers to updating. Future efforts may aim to reduce barriers and provide incentives to authors to improve updating practices.
Clinical and Biological Significance of Hepsin Overexpression in Breast Cancer
Authors: Xing Peng , Li Ji-guang , Jin Feng , Zhao Ting-ting , Liu Qun , Dong Hui-ting , Wei Xiao-lin
Published: May 2016

Objective

Although many studies have documented the tumor-promoting role of hepsin in several types of malignancies, little is known about its clinical and biological significance in breast cancer.

Materials and Methods

Hepsin expression was examined in 4 pairs of fresh breast tumor samples and corresponding nontumor breast tissues by Western blotting. Immunohistochemistry for hepsin was performed on an additional cohort of 215 archival breast cancer samples. The clinical significance of hepsin expression was analyzed. Knockdown of hepsin expression was performed in 2 breast cancer cell lines, MDA-MB-231 and HER18, with a high abundance of endogenous hepsin, and the effects of hepsin silencing on cell invasion and proliferation were evaluated.

Results

Hepsin was aberrantly overexpressed in breast cancer tissues relative to adjacent nontumor tissues. Its overexpression was significantly associated with tumor stage ( P = 0.037), lymph node metastasis ( P = 0.010), estrogen receptor positivity ( P = 0.019), and progesterone receptor positivity ( P < 0.0001) in patients with breast cancer. Down-regulation of hepsin expression by small interfering RNA (siRNA) significantly reduced cell proliferation and invasion in both the MDA-MB-231 and HER18 cells compared to nonspecific control small interference RNA.

Conclusion

Our data demonstrate that hepsin expression is frequently up-regulated in breast cancer tissues, which is associated with tumor growth and progression. Thus, inhibition of hepsin expression might be of therapeutic significance.
Vitamin D: A D-Lightful Solution for Health
Authors: Holick Michael F.
Published: May 2016

Throughout evolution, sunlight-produced vitamin D in the skin has been critically important for health. Vitamin D, known as the sunshine vitamin, is actually a hormone. Once it is produced in the skin or ingested from the diet, it is converted sequentially in the liver and kidneys to its biologically active form 1,25-dihydroxyvitamin D. This hormone interacts with its receptor in the small intestine to increase the efficiency of intestinal calcium and phosphate absorption for the maintenance of the skeleton throughout life. Vitamin D deficiency during the first few years of life results in a flattened pelvis, making it difficult for childbirth. Vitamin D deficiency causes osteopenia and osteoporosis, increasing risk of fracture. Essentially, every tissue and cell in the body has a vitamin D receptor. Therefore, vitamin D deficiency has been linked to increased risk for preeclampsia, requiring a cesarean section for birthing, multiple sclerosis, rheumatoid arthritis, types I and II diabetes, heart disease, dementia, deadly cancers, and infectious diseases. Therefore, sensible sun exposure along with vitamin D supplementation of at least 2000 IU/d for adults and 1000 IU/d for children is essential to maximize their health.
Elevated Serum Uric Acid Predicts Angiographic Impaired Reperfusion and 1-Year Mortality in ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention
Authors: Basar Nurcan , Sen Nihat , Ozcan Firat , Erden Gonul , Kanat Selcuk , Sokmen Erdogan , Isleyen Ahmet , Yuzgecer Huseyin , Ozlu Mehmet Fatih , Yildirimkaya Metin , Maden Orhan , Covic Adrian , Johnson Richard J. , Kanbay Mehmet
Published: May 2016

Background

Serum uric acid (SUA) is associated with microvascular disease that could alter coronary blood flow and prognosis. We evaluated the effects of admission SUA levels on coronary blood flow and prognosis in 185 consecutive patients with ST-segment elevation myocardial infarction (STEMI) who underwent acute primary percutaneous coronary intervention (PCI).

Methods

Patients undergoing PCI for an acute STEMI were stratified into elevated SUA (>6.5 mg/dL) and normal SUA group (≤6.5 mg/dL). Primary end points were post-PCI myocardial blood flow and in-hospital and 1-year mortality.

Results

Serum uric acid level was high in 45 patients (24%) on admission. Subjects with elevated SUA had a higher prevalence of hypertension, previous myocardial infarction, multivessel disease, and Killip functional class III or higher. Corrected thrombolysis in myocardial infarction (TIMI) frame count was longer, and mean TIMI myocardial perfusion grade was higher in patients with elevated uric acid compared with controls. Patients with elevated SUA levels had higher in-hospital (6.6% vs 2.8%, P < 0.01) and 1-year mortality (11.1% vs 5.7%, P < 0.01). Major adverse cardiac events were higher in patients with elevated SUA levels both in-hospital (11.1% vs 5.7%, P < 0.01) and at 1 year (17.7% vs 10%, P < 0.05). An elevated admission SUA level also independently predicted both 1-year mortality (odds ratio, 1.41; 95% confidence interval, 1.24-2.69) and abnormal myocardial perfusion detected by TIMI myocardial perfusion grade in STEMI patients undergoing primary PCI (odds ratio, 2.14; 95% confidence interval, 1.17-4.19, respectively).

Conclusions

Elevated SUA level on admission independently predicts impaired myocardial flow and poor prognosis in STEMI patients undergoing primary PCI.
Age- and Sex-Specific Cancer Prevention and Screening Practices among Asian Indian Immigrants in the United States
Authors: Misra Ranjita , Menon Usha , Vadaparampil Susan T. , BeLue Rhonda
Published: May 2016

Objective

The objective was to examine age- and sex-specific cancer prevention and screening practices among 1820 Asian Indian (AI) adults in the United States using items from the 2000 National Health Interview Survey Cancer Control Topical Module.

Methods

A cross-sectional study of 1820 randomly selected AIs living in 7 US cities. Data were collected via telephone interviews by trained multilingual AI staff; the response rate was 62%. The primary outcome variables were age- and sex-specific cancer screening behaviors.

Results

Most of the AIs are men, married, educated, and with some form of health insurance. One fifth reported a family history of cancer. Adherence to mammography, Papanicolaou test, and clinical breast examination was higher in contrast to low rates of breast self-examination in women. Similarly, men reported low clinical testicular examination and fecal occult blood test, although prostate-specific antigen screening was higher than the reported rates among Asian Americans. Men were more likely to get a colonoscopy than women. The length of time in the United States had a relatively weak effect, and a family history of cancer had a moderate effect on screening behavior. Education and access to health care increased the odds (2-6 times) of cancer screening in AI men and women.

Conclusions

Cancer screening varies by educational level, years lived in the United States, and access to health care, among AIs living in the United States. Differences in sociodemographic factors should be considered to predict adherence to cancer screening guidelines and also be factored into patient education in this ethnic subgroup.
The Path from Bench to Bedside: Considerations before Starting the Journey
Authors: Freeman Mason Wright , Dervan Andrew P.
Published: May 2016

Our understanding of human biology has increased tremendously for the last several decades, yet the pace at which these discoveries have translated into new therapies for patients has been frustratingly stagnant. Universities and academic health centers, as the major recipients of public investment in biomedical science, have an obligation to translate new knowledge into applications that confer human benefit. However, translating fundamental discoveries into practical applications is expensive and involves highly regulated steps with which few academic scientists have experience. Challenges in engaging universities and academic health centers in translational research include building the appropriate infrastructures for human investigation, training and stabilizing the careers of young scientists and physicians interested in the requisite work, educating academic investigators about the regulatory requirements inherent in successful therapeutic discovery and development, and finding more efficient ways to match good ideas with adequate funding resources. The purpose of this article is to examine the early-stage drug development process and evaluate the role that academia could play in it. Because interest in early-stage drug development grows among academic investigators, the need for more integrated partnerships among academia, government, and industry has become increasingly apparent.
Vitamin D and the Immune System
Authors: Aranow Cynthia
Published: May 2016

It is now clear that vitamin D has important roles in addition to its classic effects on calcium and bone homeostasis. As the vitamin D receptor is expressed on immune cells (B cells, T cells, and antigen-presenting cells), and these immunologic cells are all capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in an autocrine manner in a local immunologic milieu. Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity and an increased susceptibility to infection. As immune cells in autoimmune diseases are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with autoimmune disease may extend beyond the effects on bone and calcium homeostasis.