155 research outputs found
Comparative study on functional and structural properties of the Barbary sheep and European mouflon haemoglobins
No full textComparative study on functional and structural properties of the Barbary sheep and European mouflon haemoglobins
No full textPediococcus acidilactici GR-5 alleviates hyperuricemia by degrading purine nucleosides and improving gut microbiota metabolism
No full textAbstract Reducing intestinal absorption by degrading purine nucleosides has been shown to alleviate hyperuricemia (HUA). The probiotic Pediococcus acidilactici GR-5, derived from the traditional food “Jiangshui”, achieved efficient degradation of purine nucleosides through its unique purine nucleoside phosphorylase-DeoD. In the purine nucleosides-induced HUA mouse model, GR-5 treatment reduced serum uric acid (UA) by about 52.17%. GR-5 may improves tissue inflammatory damage by inhibiting the NLRP3 inflammatory pathway, and restored the intestinal barrier by increasing tight junction proteins Occludin and ZO-1 expression, which outperforming the allopurinol. The mechanism of UA reduction may also involves inhibiting UA synthase activity and regulating UA transporters level. GR-5 colonization in intestine increased the abundance of Lactobacillus, improved the metabolism of purine, tryptophan and bile acid by gut microbiota, and increased the level of SCFAs. Overall, GR-5 may be a potential preventive agent for improving HUA and is expected to provide a healthy option for preventing diet-induced HUA
CVS decreases hippocampal GR and FGF2 expression levels.
No full text(A) Graphical representation of the GR fold change. (B) Graphical representation of the FGF2 fold change. Bars represent means ± standard error of the mean, data points reflect individual scores.</p
Pearson correlations between GR and FGF2 fold change with depressive and anxiety-like behaviors.
No full textPearson correlations between GR and FGF2 fold change with depressive and anxiety-like behaviors.</p
Empirical Approach of Leaching Curves for Determining the Efficiency of Reclaiming Saline-Sodic Soils in Sahl El-Tina, Sinai, Egypt
No full textColumns experiment was conducted to determine desalinization and desodification leaching curves of a clay saline-sodic soil. Soil samples were collected from Sahl El-Tina plain, Northern Sinai Governorate, Egypt. Soil columns were amended with agricultural normal gypsum "NG", phosphogypsum "PG" and calcium chloride "CaCl2.2H2O". Gypsum Requirements (GR) were calculated according to USDA equation. Calculated amount of gypsum was mixed with whole soil matrix (30-cm). Leaching was done using intermittent ponding method so as to add portions to the already saturated soil columns; and obtained leachates equal to the added portions. Desalinization and desodification curves showed that all treatments reduced soil salinity and sodicity, with a superiority of calcium chloride in reducing soil salinity and sodicity. In addition, the Hoffman’s approach was adopted to estimate the leaching constant (k) of amendments. Desalinization and desodification curves showed that application of calcium chloride appears to have a strong effect on (k) values. The leaching constants (k) of control, NG, PG and CaCl2.2H2O gave averaged values of 0.39, 0.27, 0.25 and 0.19 for desalinization and 0.35, 0.28, 0.27 and 0.16 for desodification, respectively. The lower values of (k) in CaCl2.2H2O treatment depicted lower amounts of water required for leaching and reclamation compared to other treatments. This study suggests that Leaching curves represent a very good method to determine the efficiency of amendments and the optimum depth of leaching water needed for successful reclamation.
 
Genetic and Molecular Factors in Drug-Induced Liver Injury: A Review
No full textThe diagnosis of drug-induced liver injury (DILI) is challenging and based on complex diagnostic criteria. DILI falls into two main categories i) intrinsic 'dose-dependent' Type A reactions ii) 'idiosyncratic' or Type B reactions (which are usually not predictable). Idiosyncratic reactions can be immunoallergic (hypersensitivity), or metabolic, although overlap between categories can occur. The aim of this review is to summarise the general view of underlying mechanisms in DILI and to highlight individual risk factors for developing hepatotoxicity. Polymorphisms of bioactivation/ toxification pathways through CYP450 enzymes (Phase I), detoxification reactions (Phase II) and excretion/transport (Phase III) are explored together with immunological factors that might determine DILI. The importance of establishing a multidisciplinary and multi-centric network to promote the understanding and research in hepatotoxicity is underlined. Challenges such as genetic analyses for association studies and whole genome studies, pharmacogenetic testing and future approaches to study DILI are considered. Knowledge regarding these operational mechanisms could provide further insight for the prospective identification of susceptible patients at risk of developing drug-induced hepatotoxicity.
Genetic determinants of statin-associated myopathy
No full textLipid-lowering drugs, especially 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins), are widely used in the treatment of patients with increased risk of cardiovascular disease, with well-documented benefits. However, in rare cases, lipid-lowering drugs may cause myopathy or rhabdomyolysis, the risk of which is increased by certain drug-drug interactions. Polymorphisms of metabolizing pathways, including CYP, and efflux transporters, such as MDR1 and SLCO1B1, may cause intersubject variability in plasma statin levels and therefore may be responsible for susceptibility to myopathy. The aim of this review is to summarize selected genetic polymorphisms that predispose to statin-related myopathy (including combined studies of myopathy and myalgia). Genome-wide studies suggest that there is a strong candidate variant within the SLCO1B1 gene (rs4149056) for statin-associated myopathy in a UK (European) population. An enhanced understanding of statin-related myopathy may lead to safer drug development and use
Impact of a pay-for-performance incentive scheme on age, sex, and socioeconomic disparities in diabetes management in UK primary care.
No full textWe examined the impact of a major pay-for-performance initiative introduced into UK primary care in 2004 on disparities in diabetes management between age, sex, and socioeconomic groups in this retrospective cohort study. We used data from the General Practice Research Database enrolling 422 family practices. Existing disparities in risk factor management (HbA1c, blood pressure, cholesterol) narrowed between men and women. Younger patients (<45 years) with diabetes appear to have benefited less from Quality and Outcomes Framework than older patients, resulting in some widening of existing age group disparities. Patients living in affluent and deprived areas appeared to have derived a similar level of benefit from pay for performance
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database.
No full textOBJECTIVE: To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs. DESIGN: Retrospective cohort study. SETTING: UK general practice research database, 1990-2005. PARTICIPANTS: 91,521 people with diabetes. MAIN OUTCOME MEASURES: Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin. RESULTS: 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18,548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P<0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded. CONCLUSIONS: Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone; although this requires replication in other studies, it may have implications for prescribing within this class of drugs
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