Ostéochondrose cervicothoracique chez le chameau : étude comparée des lésions des disques intervertébraux

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Possible intrusive food interaction with oral dabigatran’s anticoagulant activity in a rat models

Purpose: To evaluate the synergistic or antagonistic interaction between oral dabigitran etexilate (Pradaxa) and some foods.Methods: Aqueous extracts of sweet orange, cabbage, ginger, green tea, garlic and pineapple were prepared and lyophilized, and total phenolic acids and flavonoid contents evaluated. The residues of the aqueous extracts were given daily to the rats (500 mg/kg dose, oral) 1 h after administration of dabigatran (1.83 mg/kg dose) for 14 days. Bleeding time, International Normalized Ratio (INR), prothrombin time (PT) as well as alanine  aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in blood were measured.Results: Oral administration of Pradaxa with all the test food (except  cabbage) significantly increased bleeding time, INR and PT. Pradaxa  interaction with cabbage significantly decreased bleeding tendencies but the drug did not produce any major elevation of liver enzyme levels (ALT, AST and ALP). Conversely, significant elevation in ALP level was observed only after aqueous extract of ginger was administered with Pradaxa. Green tea and garlic significantly increased ALT and AST levels.Conclusion: Synergistic interaction occurrs between dabigatran etexilate with the selected foods, but interaction with cabbage antagonistic.Keywords: Dabigatran etexilate, Anticoagulant, Foods, Liver enzymes, International Normalized Ratio, Prothrombin tim

A plate-based assay system for analyses and screening of the Leishmania major inositol phosphorylceramide synthase

Sphingolipids are key components of eukaryotic membranes, particularly the plasma membrane. The biosynthetic pathway for the formation of these lipid species is largely conserved. However, in contrast to mammals, which produce sphingomyelin, organisms such as the pathogenic fungi and protozoa synthesize inositol phosphorylceramide (IPC) as the primary phosphosphingolipid. The key step involves the reaction of ceramide and phosphatidylinositol catalysed by IPC synthase, an essential enzyme with no mammalian equivalent encoded by the AUR1 gene in yeast and recently identified functional orthologues in the pathogenic kinetoplastid protozoa. As such this enzyme represents a promising target for novel anti-fungal and anti-protozoal drugs. Given the paucity of effective treatments for kinetoplastid diseases such as leishmaniasis, there is a need to characterize the protozoan enzyme. To this end a fluorescent-based cell-free assay protocol in a 96-well plate format has been established for the Leishmania major IPC synthase. Using this system the kinetic parameters of the enzyme have been determined as obeying the double displacement model with apparent Vmax = 2.31 pmol min−1 U−1. Furthermore, inhibitory substrate analogues have been identified. Importantly this assay is amenable to development for use in high-throughput screening applications for lead inhibitors and as such may prove to be a pivotal tool in drug discovery

Access to care for non-communicable diseases in Mosul, Iraq between 2014 and 2017: a rapid qualitative study.

During June 2014 to April 2017, the population of Mosul, Iraq lived in a state of increasing isolation from the rest of Iraq due to the city's occupation by the Islamic State group. As part of a study to develop a generalisable method for estimating the excess burden of non-communicable diseases (NCDs) in conflict-affected settings, in April-May 2017 we conducted a brief qualitative study of self-reported care for NCDs among 15 adult patients who had fled Mosul and presented to Médecins Sans Frontières clinics in the Kurdistan region with hypertension and/or diabetes. Participants reported consistent barriers to NCD care during the so-called Islamic State period, including drug shortages, insecurity and inability to afford privately sold medication. Coping strategies included drug rationing. By 2016, all patients had completely or partially lost access to care. Though limited, this study suggests a profound effect of the conflict on NCD burden

N-glycosylation in the thermoacidophilic archaeon <i>Sulfolobus acidocaldarius</i> involves a short dolichol pyrophosphate carrier

N-glycosylation is a post-translational modification that occurs across evolution. In the thermoacidophilic archaea Sulfolobus acidocaldarius, glycoproteins are modified by an N-linked tribranched hexasaccharide reminiscent of the N-glycans assembled in Eukarya. Previously, hexose-bearing dolichol phosphate was detected in a S. acidocaldarius Bligh-Dyer lipid extract. Here, we used a specialized protocol for extracting lipid-linked oligosaccharides to detect a dolichol pyrophosphate bearing the intact hexasaccharide, as well as its biosynthetic intermediates. Furthermore, evidence for N-glycosylation of two S. acidocaldarius proteins by the same hexasaccharide and its derivatives was collected. These findings thus provide novel insight into archaeal N-glycosylation

S. Cheema et al .

Objectives Oral health is a crucial determinant of quality of life. We aimed to determine oral health condition and factors associated with poor oral status in the adult national population of Qatar. Methods We used data from the World Health Organization supported STEPS (STEPwise approach to Surveillance) Survey conducted by the Supreme Council of Health, Qatar in 2012. A total of 2,496 Qataris (1,053 men, 1,443 women) answered the national survey. The Rao-Scott Chi-Square test was used to analyze oral health characteristics and multinomial logistic regression to assess risk factors. Results The self-perceived oral status of approximately 40 percent of respondents was either "average" or "poor" rather than "good." Poor oral status was more often reported by women (OR = 1.93; 95%CI = 1.30-2.80), by older (OR = 3.38; 95%CI = 1.59-7.19) and less educated respondents (OR = 3.58; 95%CI = 2.15-5.96). Other risk groups included people with diabetes (OR = 1.87; 95%CI = 1.24-2.81), smokeless tobacco users (OR = 3.90; 95%CI = 1.75-8.68), or ever tobacco users (OR = 1.66; 95%CI = 1.03-2.67). Oral health status appeared to be independent of diet, BMI status, and history of hypertension. Difficulties and behaviors related to oral health were more frequently reported by women than by men. These included pain (P < 0.001), difficulty chewing (P < 0.001), and discomfort over appearance of teeth (P < 0.001). Participants used toothbrushes, toothpicks, dental floss, and miswak to maintain oral hygiene. Conclusion Our results provide evidence that oral health remains a public health concern in Qatar

AglH, a thermophilic UDP‑<i>N</i>‑acetylglucosamine‑1‑phosphate:dolichyl phosphate GlcNAc‑1‑phosphotransferase initiating protein<i> N</i>‑glycosylation pathway in <i>Sulfolobus acidocaldarius</i>, is capable of complementing the eukaryal Alg7

AglH, a predicted UDP-GlcNAc-1-phosphate:dolichyl phosphate GlcNAc-1-phosphotransferase, is initiating the protein N-glycosylation pathway in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. AglH successfully replaced the endogenous GlcNAc-1-phosphotransferase activity of Alg7 in a conditional lethal Saccharomyces cerevisiae strain, in which the first step of the eukaryal protein N-glycosylation process was repressed. This study is one of the few examples of cross-domain complementation demonstrating a conserved polyprenyl phosphate transferase reaction within the eukaryal and archaeal domain like it was demonstrated for Methanococcus voltae (Shams-Eldin et al. 2008). The topology prediction and the alignment of the AglH membrane protein with GlcNAc-1-phosphotransferases from the three domains of life show significant conservation of amino acids within the different proposed cytoplasmic loops. Alanine mutations of selected conserved amino acids in the putative cytoplasmic loops II (D(100)), IV (F(220)) and V (F(264)) demonstrated the importance of these amino acids for cross-domain AlgH activity in in vitro complementation assays in S. cerevisiae. Furthermore, antibiotic treatment interfering directly with the activity of dolichyl phosphate GlcNAc-1-phosphotransferases confirmed the essentiality of N-glycosylation for cell survival

Biochemical evidence for an alternate pathway in N-linked glycoprotein biosynthesis

Asparagine-linked glycosylation is a complex protein modification conserved among all three domains of life. Herein we report the in vitro analysis of N-linked glycosylation from the methanogenic archaeon Methanococcus voltae. Using a suite of synthetic and semisynthetic substrates, we show that AglK initiates N-linked glycosylation in M. voltae through the formation of α-linked dolichyl monophosphate N-acetylglucosamine, which contrasts with the polyprenyl diphosphate intermediates that feature in both eukaryotes and bacteria. Notably, AglK has high sequence homology to dolichyl phosphate β-glucosyltransferases, including Alg5 in eukaryotes, suggesting a common evolutionary origin. The combined action of the first two enzymes, AglK and AglC, afforded an α-linked dolichyl monophosphate glycan that serves as a competent substrate for the archaeal oligosaccharyl transferase AglB. These studies provide what is to our knowledge the first biochemical evidence revealing that, despite the apparent similarity of the overall pathways, there are actually two general strategies to achieve N-linked glycoproteins across the domains of life.National Institutes of Health (U.S.) (Grant GM039334

Approachability in Stackelberg Stochastic Games with Vector Costs

The notion of approachability was introduced by Blackwell [1] in the context of vector-valued repeated games. The famous Blackwell's approachability theorem prescribes a strategy for approachability, i.e., for `steering' the average cost of a given agent towards a given target set, irrespective of the strategies of the other agents. In this paper, motivated by the multi-objective optimization/decision making problems in dynamically changing environments, we address the approachability problem in Stackelberg stochastic games with vector valued cost functions. We make two main contributions. Firstly, we give a simple and computationally tractable strategy for approachability for Stackelberg stochastic games along the lines of Blackwell's. Secondly, we give a reinforcement learning algorithm for learning the approachable strategy when the transition kernel is unknown. We also recover as a by-product Blackwell's necessary and sufficient condition for approachability for convex sets in this set up and thus a complete characterization. We also give sufficient conditions for non-convex sets.Comment: 18 Pages, Submitted to Dynamic Games and Application