Ensemble Analysis of Angiogenic Growth in Three-Dimensional Microfluidic Cell Cultures

We demonstrate ensemble three-dimensional cell cultures and quantitative analysis of angiogenic growth from uniform endothelial monolayers. Our approach combines two key elements: a micro-fluidic assay that enables parallelized angiogenic growth instances subject to common extracellular conditions, and an automated image acquisition and processing scheme enabling high-throughput, unbiased quantification of angiogenic growth. Because of the increased throughput of the assay in comparison to existing three-dimensional morphogenic assays, statistical properties of angiogenic growth can be reliably estimated. We used the assay to evaluate the combined effects of vascular endothelial growth factor (VEGF) and the signaling lipid sphingoshine-1-phosphate (S1P). Our results show the importance of S1P in amplifying the angiogenic response in the presence of VEGF gradients. Furthermore, the application of S1P with VEGF gradients resulted in angiogenic sprouts with higher aspect ratio than S1P with background levels of VEGF, despite reduced total migratory activity. This implies a synergistic effect between the growth factors in promoting angiogenic activity. Finally, the variance in the computed angiogenic metrics (as measured by ensemble standard deviation) was found to increase linearly with the ensemble mean. This finding is consistent with stochastic agent-based mathematical models of angiogenesis that represent angiogenic growth as a series of independent stochastic cell-level decisions

Topography of Extracellular Matrix Mediates Vascular Morphogenesis and Migration Speeds in Angiogenesis

The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing, muscle repair, morphogenesis, new blood vessel growth, and cancer invasion. In this study, we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in the context of angiogenesis. To do this, we validate our spatio-temporal mathematical model of angiogenesis against empirical data, and within this framework, we vary the density of the matrix fibers to simulate different tissue environments and to explore the possibility of manipulating the extracellular matrix to achieve pro- and anti-angiogenic effects. The model predicts specific ranges of matrix fiber densities that maximize sprout extension speed, induce branching, or interrupt normal angiogenesis, which are independently confirmed by experiment. We then explore matrix fiber alignment as a key factor contributing to peak sprout velocities and in mediating cell shape and orientation. We also quantify the effects of proteolytic matrix degradation by the tip cell on sprout velocity and demonstrate that degradation promotes sprout growth at high matrix densities, but has an inhibitory effect at lower densities. Our results are discussed in the context of ECM targeted pro- and anti-angiogenic therapies that can be tested empirically

Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection

Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

EFFECT OF SOME TOXIC FACTORS IN RAW BEANS ON ORGANS OF RATS

Autoclave d dry gr ound beans and ethanol ext r acted g round beans which con t a i n t wo-thi r d of t he haemagglutinin , and one-quarter o f the t rypsin i nhibitors with 80% o f its origi nal t annin we re f ed t o rat s for determinati on the Nitr ogen digestibi l i ty . The toxic f act or s of bea n s k i l led all the a nimals be fore t he complet ion o f t he 10- day per iod ass ay . Fecal DNA of ani mals were twice gre at e r compare d with c a se i n and none-protein fed ani ma l s . Some c ahnges were observed on organs we ight(panc reas,spl e en , l iver , kidneys and adrenals ) compared with cont ro- Is . &nbsp

Evaluation of pentoxifylline in the prevention of contrast-induced nephropathy in patients undergoing primary percutaneous coronary intervention

Background: As percutaneous coronary intervention (PCI) technologies confer increasing patient advantage, the use of iodinated contrast media for diagnostic and interventional procedures is increased. Although contrast media obstacles are transient and mild, contrast-induced nephropathy (CIN) negatively affects long-term patient mortality. PCI creates a high-risk condition for the incidence of CIN even in patients with a normal renal function. Pentoxifylline (PTX) with a variety of mechanisms may prevent CIN. We sought to assess the positive effect of PTX administration at the beginning prior to contrast media use to 24 hours after PCI to prevent CIN in patients with STEMI. Methods: In this double-blind, single-center, clinical trial, we randomly assigned 296 consecutive patients to the control group (n=148) without PTX and the case group (n=148) with PTX 400 mg/tid at the time of hospitalization to 24 hours after the procedure. Serum creatinine was measured before and 48 hours after the procedure. The occurrence of CIN within 48 hours was our end point. CIN was defined as a 0.5 mg/dL increase or more in serum creatinine or a 25 increase or more above baseline serum creatinine. Results: A total of 296 patients were enrolled in this trial and were randomly assigned to receive either primary PCI plus PTX or only primary PCI. Out of 148 patients who received PTX, only 12.2 were seen to have CIN incidence (>0.5 mg/dL or a 25 increase in the Cr level); however, the difference between the 2 groups regarding CIN was not significant (P=0.4). Out of the 296 patients, only 20 were found to have chronic kidney disease (CKD) (CKD was defined as baseline Cr>1.5); and of those patients, 3 (15) showed CIN incidence. Nevertheless, the difference between the 2 groups regarding CIN incidence was not significant (P=0.7). The regression test showed that between all confounding factors in the 2 groups of PTX positive and negative, sex and ejection fraction had positive effects on the rise in the Cr level and, consequently, the incidence of CIN (95 CI: 1.60 to 30.85; P=0.01 and 95 CI: 0.92 to 1; P=0.05). Conclusions: Administration of oral PTX to patients with increased risk for CIN scheduled for primary PCI may not reduce the Cr level and thus the occurrence of CIN. Given the higher prevalence of hypotension in the patients without PTX, higher prevalence of CKD in the patients without PTX, and absence of significant difference between the 2 groups regarding the incidence of CIN, PTX had no preventive effect on CIN occurrence in STEMI. Among all factors influencing CIN occurrence, sex and ejection fraction had positive effects on the rise in the Cr level. © 2015, Iranian Heart Association. All rights reserved

Prevalence and risk factors of hepatitis B infection in pregnant women of Iran: A systematic review and meta-analysis

Introduction: Perinatal transmission is one of the most common routes of hepatitis B virus (HBV) transmission in the worldwide. In Iran, more than 50 of HBV carriers have received the infection in this route. Therefore, this review study was performed with aim to determine the prevalence and risk factors of HBV infection in pregnant women of Iran. Methods: Current study was conducted based on PRISMA checklist for systematic review and meta-analysis studies. To access to the English and Persian documents, two independent authors searched Scopus, PubMed, ScienceDirect, Cochrane, Web of Science (ISI), Springer, Online Library Wiley, Magiran, Iranmedex, SID, Medlib, IranDoc and Google Scholar search engine up to January 2016 by using Mesh keywords including: Prevalence, Hepatitis B, Pregnant women, Pregnancy, Risk Factors, HBsAg and Iran. Data was analyzed using the random-effects model for HBV prevalence and fixed-effects model for risk factors of HBV via Stata software (Version 11.2). Results: A total of 36 eligible studies with sample size of 64,195 pregnant women in Iran, HBV prevalence was estimated 0.5. Minimum and maximum of this range were related to the North (0.4) and East (1.6) of the Iran. HBV prevalence in urban and rural pregnant women was estimated 1.1 and 1.2, respectively. HBV prevalence among housewife pregnant women was 1.7 and employee pregnant women was 0.1. The frequency of HBsAb>10 mIU/ml in Iranian pregnant women were calculated 40. Among the risk factors, illiteracy, occupation, blood transfusion, abortion and husband addiction were significant related with prevalence of HBV (P0.05). Conclusion: The lowest prevalence of HBV in Iran was related to pregnant women and less than the general population. History of blood transfusions, husband addiction, illiteracy, occupation and abortion are associated with HBV in Iranian pregnant women. © 2016, Mashhad University of Medical Sciences. All rights reserved

The Frequency of Vitamin D Deficiency among Referred to Clinical Laboratories in Eyvan City during 2015 and 2016- Ilam province, Iran

Introduction: Vitamin D deficiency (VDD) causes same diseases such as osteoporosis, osteomalacia, and fractures, and also it is shown that Vitamin D deficiency could lead to some cardiovascular disease, diabetes and many types of cancer. Therefore, this study aimed to determine the frequency of vitamin D deficiency among referring to laboratories in Eyvan city during 2015 and 2016. Methods: A cross-sectional study was conducted in 2014 and 2015 on patients who were referred to the laboratories at Eyvan city. Serum levels of 25OHD were determined using a ELISA assay. The data were analyzed SPSS 17 software using descriptive and analytical tests. Results: Out of 2 919 participants, 2053 patients were women. The average age was 36.25±17.1 (range 1-92) yrs. The overall prevalence of vitamin D deficiency in the patients admitted to the medical laboratories was estimated that approximately 62%. The prevalence severe and moderate vitamin D deficiency was calculated 10.4 and 51.5, respectively. The prevalence of vitamin D deficiency among the ages 1-6, 7-18, 19-60 and over 60 years was estimated 45%, 59%, 64% and 58%, respectively. The mean vitamin D concentration was 36.25±18.79 ng/ml. The relationship between deficiency of vitamin D with age and gender was statistically significant (P=000). Conclusion: Vitamin D deficiency prevalence is high, so the intervention plan seems essential to avoid complications of vitamin D deficiency such as medication treatment and establishing nationally-mandated food fortification programs to enhance the intake of vitamin D