Altered cyclooxygenase-1 and enhanced thromboxane receptor activities underlie attenuated endothelial dilatory capacity of omental arteries in obesity

AIMS: Obesity is a risk factor for endothelial dysfunction, the severity of which is likely to vary depending on extent and impact of adiposity on the vasculature. This study investigates the roles of cyclooxygenase isoforms and thromboxane receptor activities in the differential endothelial dilatory capacities of arteries derived from omental and subcutaneous adipose tissues in obesity. MAIN METHODS: Small arteries were isolated from omental and subcutaneous adipose tissues obtained from consented morbidly obese patients (n = 65, BMI 45 ± 6 kg m-2 [Mean ± SD]) undergoing bariatric surgery. Relaxation to acetylcholine was studied by wire myography in the absence or presence of indomethacin (10 μM, cyclooxygenase inhibitor), FR122047 (1 μM, cyclooxygenase-1 inhibitor), Celecoxib (4 μM, cyclooxygenase-2 inhibitor), Nω-Nitro-L-arginine methyl ester (L-NAME, 100 μM, nitric oxide synthase inhibitor) or combination of apamin (0.5 μM) and charybdotoxin (0.1 μM) that together inhibit endothelium-derived hyperpolarizing factor (EDHF). Contractions to U46619 (thromboxane A2 mimetic) were also studied. KEY FINDINGS: Acetylcholine relaxation was significantly attenuated in omental compared with subcutaneous arteries from same patients (p < 0.01). Indomethacin (p < 0.01) and FR122047 (p < 0.001) but not Celecoxib significantly improved the omental arteriolar relaxation. Cyclooxygenase-1 mRNA and U46619 contractions were both increased in omental compared with subcutaneous arteries (p < 0.05). L-NAME comparably inhibited acetylcholine relaxation in both arteries, while apamin+charybdotoxin were less effective in omental compared with subcutaneous arteries. SIGNIFICANCE: The results show that the depot-specific reduction in endothelial dilatory capacity of omental compared with subcutaneous arteries in obesity is in large part due to altered cyclooxygenase-1 and enhanced thromboxane receptor activities, which cause EDHF deficiency

Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report

BACKGROUND: Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation. CASE PRESENTATION: A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system. CONCLUSION: Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately

Severe anaemia is associated with a higher risk for preeclampsia and poor perinatal outcomes in Kassala hospital, eastern Sudan

<p>Abstract</p> <p>Background</p> <p>Anaemia during pregnancy is major health problem. There is conflicting literature regarding the association between anaemia and its severity and maternal and perinatal outcomes.</p> <p>Methods</p> <p>This is a retrospective case-control study conducted at Kassala hospital, eastern Sudan. Medical files of pregnant women with severe anaemia (haemoglobin (Hb) < 7 g/dl, n = 303) who delivered from January 2008 to December 2010 were reviewed. Socio-demographic and obstetric data were analysed and compared with a similar number of women with mild/moderate anaemia (Hb = 7-10.9 g/dl, n = 303) and with no anaemia (Hb > 11 g/dl, n = 303). Logistic regression analysis was performed separately for each of the outcome measures: preeclampsia, eclampsia, preterm birth, low birth weight (LBW) and stillbirth.</p> <p>Results</p> <p>There were 9578 deliveries at Kassala hospital, 4012 (41.8%) women had anaemia and 303 (3.2%) had severe anaemia. The corrected risk for preeclampsia increased only in severe anaemia (OR = 3.6, 95% CI: 1.4-9.1, <it>P </it>= 0.007). Compared with women with no anaemia, the risk of LBW was 2.5 times higher in women with mild/moderate anaemia (95% CI: 1.1-5.7), and 8.0 times higher in women with severe anaemia (95% CI: 3.8-16.0). The risk of preterm delivery increased significantly with the severity of anaemia (OR = 3.2 for women with mild/moderate anaemia and OR = 6.6 for women with severe anaemia, compared with women with no anaemia). The corrected risk for stillbirth increased only in severe anaemia (OR = 4.3, 95% CI: 1.9-9.1, <it>P </it>< 0.001).</p> <p>Conclusions</p> <p>The greater the severity of the anaemia during pregnancy, the greater the risk of preeclampsia, preterm delivery, LBW and stillbirth. Preventive measures should be undertaken to decrease the prevalence of anaemia in pregnancy.</p

Gendered Representations of Male and Female Social Actors in Iranian Educational Materials

This research investigates the representations of gendered social actors within the subversionary discourse of equal educational opportunities for males and females in Iranian English as a Foreign Language (EFL) books. Using critical discourse analysis (CDA) as the theoretical framework, the authors blend van Leeuwen’s (Texts and practices: Readings in critical discourse analysis, Routledge, London, 2003) ‘Social Actor Network Model’ and Sunderland’s (Gendered discourses, Palgrave Macmillan, Hampshire, 2004) ‘Gendered Discourses Model’ in order to examine the depictions of male and female social actors within this gendered discourse. The gendered discourse of equal opportunities was buttressed by such representations within a tight perspective in proportion to gender ideologies prevailing in Iran. Resorting to CDA, we can claim that resistance against such gendered discourse in Iranian EFL textbooks militates against such gender norms. These representations of male and female social actors in school books are indicative of an all-encompassing education, reinforcing that the discourse of equal opportunities is yet to be realized in the education system of Iran

Methodology for the reduction and integration of data in the performance measurement of industries cement plants

The investigation responded to the need outlined by directive and interested parts, in relation to the lack of mechanisms for the administration control and the need to reduce the amount of data when making measurements of performance in the cement industry. Throughout the employment of an outlined methodology, it was obtained an Integral Index of Acting that relates to the aspects that controlled the acting of the processes in function of managerial strategies, of easy mensuration as a result, automatic and that it facilitates to summarize a big amount of criteria and data, through their standardization, and thus the realization of comparisons with other production plants

Scrotal calcinosis due to resorption of cyst walls: a case report

<p>Abstract</p> <p>Introduction</p> <p>Scrotal calcinosis is a rare benign entity defined as the presence of multiple calcified nodules within the scrotal skin. There are controversies about the origin of this entity. In fact, it is still debatable whether scrotal calcinosis is an idiopathic growth or dystrophic calcification of dartoic muscles. It is also unclear whether scrotal calcinosis originates from inflammation of epidermal cysts affected by mild to moderate inflammation of mononuclear cells, from foreign body granuloma formation followed by resorption of cyst walls or from eccrine epithelial cysts.</p> <p>Case presentation</p> <p>We report a 41-year-old male Turkish patient presenting with a 10-year history of scrotal tumours increasing slowly in size and number. Histopathologically, there was no epithelial lining around the calcified nodules, but there was fibrosis adjacent to atrophic stratified squamous epithelium.</p> <p>Conclusion</p> <p>Results of histopathological examinations suggested that scrotal calcinosis might have been due to resorption of cyst walls. Surgery remains the key for this problem. In cases of non-massive scrotal calcinosis, like the case presented here, excision of the nodules from the affected part of the scrotal wall and repairing the defect with horizontal stitches offer good cosmetic results without relapse.</p

Optimal Homogenization of Perfusion Flows in Microfluidic Bio-Reactors: A Numerical Study

In recent years, the interest in small-scale bio-reactors has increased dramatically. To ensure homogeneous conditions within the complete area of perfused microfluidic bio-reactors, we develop a general design of a continually feed bio-reactor with uniform perfusion flow. This is achieved by introducing a specific type of perfusion inlet to the reaction area. The geometry of these inlets are found using the methods of topology optimization and shape optimization. The results are compared with two different analytic models, from which a general parametric description of the design is obtained and tested numerically. Such a parametric description will generally be beneficial for the design of a broad range of microfluidic bioreactors used for, e.g., cell culturing and analysis and in feeding bio-arrays

The role of clathrin in post-golgi trafficking in toxoplasma gondii

Apicomplexan parasites are single eukaryotic cells with a highly polarised secretory system that contains unique secretory organelles (micronemes and rhoptries) that are required for host cell invasion. In contrast, the role of the endosomal system is poorly understood in these parasites. With many typical endocytic factors missing, we speculated that endocytosis depends exclusively on a clathrin-mediated mechanism. Intriguingly, in Toxoplasma gondii we were only able to observe the endogenous clathrin heavy chain 1 (CHC1) at the Golgi, but not at the parasite surface. For the functional characterisation of Toxoplasma gondii CHC1 we generated parasite mutants conditionally expressing the dominant negative clathrin Hub fragment and demonstrate that CHC1 is essential for vesicle formation at the trans-Golgi network. Consequently, the functional ablation of CHC1 results in Golgi aberrations, a block in the biogenesis of the unique secretory microneme and rhoptry organelles, and of the pellicle. However, we found no morphological evidence for clathrin mediating endocytosis in these parasites and speculate that they remodelled their vesicular trafficking system to adapt to an intracellular lifestyle

Promiscuous prediction and conservancy analysis of CTL binding epitopes of HCV 3a viral proteome from Punjab Pakistan: an In Silico Approach

<p>Abstract</p> <p>Background</p> <p>HCV is a positive sense RNA virus affecting approximately 180 million people world wide and about 10 million Pakistani populations. HCV genotype 3a is the major cause of infection in Pakistani population. One of the major problems of HCV infection especially in the developing countries that limits the limits the antiviral therapy is the long term treatment, high dosage and side effects. Studies of antigenic epitopes of viral sequences of a specific origin can provide an effective way to overcome the mutation rate and to determine the promiscuous binders to be used for epitope based subunit vaccine design. An <it>in silico </it>approach was applied for the analysis of entire HCV proteome of Pakistani origin, aimed to identify the viral epitopes and their conservancy in HCV genotypes 1, 2 and 3 of diverse origin.</p> <p>Results</p> <p>Immunoinformatic tools were applied for the predictive analysis of HCV 3a antigenic epitopes of Pakistani origin. All the predicted epitopes were then subjected for their conservancy analysis in HCV genotypes 1, 2 and 3 of diverse origin (worldwide). Using freely available web servers, 150 MHC II epitopes were predicted as promiscuous binders against 51 subjected alleles. E2 protein represented the 20% of all the predicted MHC II epitopes. 75.33% of the predicted MHC II epitopes were (77-100%) conserve in genotype 3; 47.33% and 40.66% in genotype 1 and 2 respectively. 69 MHC I epitopes were predicted as promiscuous binders against 47 subjected alleles. NS4b represented 26% of all the MHC I predicted epitopes. Significantly higher epitope conservancy was represented by genotype 3 i.e. 78.26% and 21.05% for genotype 1 and 2.</p> <p>Conclusions</p> <p>The study revealed comprehensive catalogue of potential HCV derived CTL epitopes from viral proteome of Pakistan origin. A considerable number of predicted epitopes were found to be conserved in different HCV genotype. However, the number of conserved epitopes in HCV genotype 3 was significantly higher in contrast to its conservancy in HCV genotype 1 and 2. Despite of the lower conservancy in genotype 1 and 2, all the predicted epitopes have important implications in diagnostics as well as CTL-based rational vaccine design, effective for most population of the world and especially the Pakistani Population.</p

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation