Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty

Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty.     

Ethnobotanical Study of Medicinal Plants Used by Kurd Tribe in Dehloran and Abdanan Districts,Ilam Province,Iran

This paper provides significant ethnobotanical information on pharmaceutical plant uses, where some degree of acculturation exists, so that there is urgency in recording such data. The aim of this work is to catalogue, document, and make known the uses of plants for folk medicine in Dehloran and Abdanan districts, Ilam Province, Iran. An analysis was made of the species used, parts of the plant employed, preparation methods, administration means, and the ailments treated in relation to pathological groups. A folk botanical survey was carried out from February 2007 to October 2009. The information was collected from 81 persons (60% men and 40% women) in 20 villages. The informants reported data on 122 species, belonging to 49 botanical families, were claimed as medicinal. This work is focused on human medicinal plant uses, which represent 95% of the pharmaceutical uses. The most commonly represented families were Asteraceae (37.5%), Lamiaceae (20.8%), Rosaceae (18.7%), Fabaceae (16.7%) and Apiaceae (14.6%). Some of the uses were found to be new when compared with published literature on ethnomedicine of Iran. The folk knowledge about medicinal plant use is still alive in the studied region, and a number of scarcely reported plant uses has been detected, some of them with promising phytotherapeutical applications. The results of the study reveal that some of species play an important role in primary healthcare system of these tribal communities.     

The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure

OBJECTIVES: The role of atrial myocytes and extracellular matrix (ECM) changes in atrial chamber remodeling was studied in a canine model of heart failure (HF). BACKGROUND: Cardiac remodeling is a key process mediating the progression of HF. Studies of the structural mechanisms of cardiac remodeling have been limited to the left ventricle. The structural alterations associated with atrial chamber remodeling in evolving HF have not been studied. METHODS: Age- and weight-matched dogs were subjected to right ventricular pacing (240 beats/min) for one and three weeks to produce early and severe HF, respectively. Atrial tissues were assessed for myocyte and ECM changes. RESULTS: Right atrial and left atrial (LA) pressures were significantly increased in early and severe HF. The LA wall tension index was significantly increased at both HF stages by 116% and 443%, respectively. Atrial collagen synthesis and degradation were significantly increased in severe HF. Gelatinase activity was significantly increased at both early and severe stages of HF. Gelatin zymography showed increased matrix metalloproteinases (MMP)-9 with early HF and increased MMP-2 with severe HF. The LA wall tension index was significantly correlated with gelatinase activity and collagen synthesis. Although total atrial collagen content was not changed, disarray of collagen fibers was observed. Atrial myocyte hypertrophy without evidence of apoptosis was also present in severe HF. CONCLUSIONS: There is marked atrial chamber remodeling in canine pacing-induced HF, which is characterized by myocyte hypertrophy and dynamic collagen turnover. Atrial remodeling may contribute to the development of atrial arrhythmias and pulmonary hypertension and could offer a novel therapeutic target.     

Effect of thymol and carvacrol on nutrient digestibility in rams fed high or low concentrate diets

Published data on the effects of essential oils (EO) on in vivo nutrient digestibility in sheep are contradictory. In 2 experiments, the effect of thymol and carvacrol on nutrient digestibility was studied in sheep fed with high (70%) or low (52%) concentrate diets, using incomplete Latin Square designs. The essential oils were mixed with the concentrate portion of the diet at the rate of 0.0, 0.3, or 0.6 g per kg dry matter (DM) diet. Supplementation of thymol had no significant effect on digestibility of dry matter (DM), organic matter (OM), crude protein (CP) and acid detergent fiber (ADF). The main effect of thymol on neutral detergent fiber (NDF) and ether extract (EE) digestibility and on nitrogen balance (NB) was significant (P<0.05), but within each level of dietary concentrate no significant differences were observed for these measurements. Overall, ruminal ammonia concentration was higher (P<0.05) in both HCD and LCD lambs receiving 0.3 mg thymol per kg diet. Supplementation of carvacrol had no significant effect on nutrient digestibility. The main effect of carvacrol on ruminal ammonia levels and NB was significant, but within each level of dietary concentrate no significant differences were observed in ammonia levels and NB. Inclusion of 0.3 g/kg diet DM of carvacrol or thyme was more effective than 0.6 g/kg diet DM in terms of NB but neither dose affected nutrient digestibility. Future research should determine the long-term effects of essential oils on digestibility and performance in sheep, before recommendation can be made for their use under practical husbandry conditions.Key Words: Carvacrol, Digestibility, Essential oils, Sheep, Thymol     

Efficacy and safety of rituximab therapy in patients with systemic sclerosis disease (SSc): systematic review and meta-analysis

Clinical Rheumatology - The clinical benefits of rituximab in systemic sclerosis (SSc) are still contentious. The present meta-analysis aimed to systematically assess rituximab’s safety and...     

Androgen receptor gene and sex-specific Alzheimer's disease

Women are at a 2-fold risk of developing late-onset Alzheimer's disease (AD) (onset at 65 years of age or older) compared with men. During perimenopausal years, women undergo hormonal changes that are accompanied by metabolic, cardiovascular, and inflammatory changes. These all together have been suggested as risk factors for late-onset AD. However, not all perimenopausal women develop AD; we hypothesize that certain genetic factors might underlie the increased susceptibility for developing AD in postmenopausal women. We investigated the Androgen Receptor gene (AR) in a clinical cohort of male and female AD patients and normal control subjects by sequencing all coding exons and evaluating the length and distribution of the CAG repeat in exon 1. We could not establish a correlation between the repeat length, sex, and the disease status, nor did we identify possible pathogenic variants. AR is located on the X chromosome; to assess its role in AD, X-inactivation patterns will need to be studied to directly correlate the actual expressed repeat length to a possible sex-specific phenotypic effect.     

Hip and knee muscle torque and its relationship with dynamic balance in chronic ankle instability,copers and controls

ObjectivesWe compared hip and knee isometric muscle torque between individuals with chronic ankle instability (CAI), those who have sustained one ankle sprain with no ongoing problems (copers) and healthy controls. Our secondary objective was to compare balance between groups and investigate the relationship between muscle torque and balance.DesignCross-sectional study.Methods22 CAI, 20 copers and 22 uninjured participants were tested. Isometric torque (normalised to body mass (Nm/kg)) was measured using a rigidly-fixated hand-held dynamometer. Balance was assessed with the Y-balance test.ResultsKnee and hip flexor and extensor, and hip adductor and abductor muscle torque was less in individuals with CAI compared to controls (standardised mean difference (SMD) >1.2). Hip and knee flexor and extensor muscle torque was less in CAI participants than copers (SMD: 0.69–1.1). Hip external and internal rotator torque did not differ between groups. There was no difference in hip or knee muscle torque between controls and copers (SMD: 0.01–0. 54). Balance was impaired in CAI participants compared to copers and controls in all directions. There was a strong positive correlation between posterolateral Y-balance test performance and torque of the hip adductors (r = 0.53), flexors (r = 0.52) and extensors (r = 0.50).ConclusionsIndividuals with CAI have weak knee and hip muscles compared to copers and controls. Hip strength was shown to be related to posterolateral balance performance. Future studies may investigate the effect of hip and knee strengthening exercise on ongoing ankle problems, such as episodic giving way in individuals with CAI.     

Is the IL-10 −819 Polymorphism Associated with Visceral Leishmaniasis?

Previous investigations demonstrated that immune responses play critical roles in the defense against visceral leishmaniasis (VL). A key regulator of immune responses is the cytokine, IL-10 and polymorphisms within its promoter which could alter its expression. Thus, the aim of this study was to examine the correlation between polymorphism at the ?819 position of the IL-10 gene and VL in a selected Iranian population. This cross-sectional study was performed on 100 patients with clinical presentation of VL and seropositive for the leishmania (group 1), 62 patients without clinical presentation but seropositive (group 2), and 128 healthy controls (group 3). The IL-10 ?819 polymorphism was evaluated using the PCR-RFLP technique. The anti-leishmania antibody titration was assessed using an immunofluorescence assay. Our results showed that the polymorphism at IL-10 ?819 (C/T) position was significantly associated with VL, and C/T genotype was significantly higher in VL patients when compared to groups 2 and 3 (p?<?0.001). However, the results demonstrated that the C and T alleles were not associated with VL (p?=?0.855). The data presented here confirm the results of previous reports that polymorphisms at the ?819 position of the IL-10 gene can influence susceptibility to VL suggesting that the C/T genotype may be considered as a risk factor for the disease.