1,914 research outputs found

    HLA-DRB1 alleles in children with post-streptococcal acute glomerulonephritis

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    To investigate the association between HLA-DRB1 alleles and post-streptococcal acuteglomerulonephritis (PSAGN), 32 children withPSAGN and 380 healthy subjects from the samelocality were typed for DRB1alleles usingpolymerase chain-reverse hybridization technique.Patients with PSAGN have significantly increasedfrequency of both DRB1* 03011 (46.9 vs. 19.2% incontrols, P = 0.00025) and DRB1* 1105 (31.1 vs.15.6% in controls, P = 0.0097). However, aftercorrection of P values, only the difference for DRB1*03011 remains significant (P = 0.025). Their relativerisks are significantly high [3.71, confidence interval(Cl) = 1.8-7.8, and 3.57, Cl = 1.4-8.9 respectively].No significant differences in the frequency of bothalleles arc observed among patients with differentgrades of hypertension, proteinuria or hematuria.Conclusions: DRB1* 03011, and presumably 1105,alleles confer susceptibility to PSAGN. However theseverity of the disease is not determined by these twoalleles

    Averrhoa carambola leaves prevent dyslipidemia and oxidative stress in a rat model of poloxamer-407-induced acute hyperlipidemia

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    Background: The star fruit [Averrhoa carambola L (Oxalidaceae)] is traditionally used in the treatment of many ailments in many countries. It possesses several pharmacological activities, including antioxidant and anti-inflammatory effects. However, it contains the neurotoxic caramboxin and its high content of oxalic acid limits its consumption by individuals with compromised kidney function. This study assessed the anti-hyperlipidemic and antioxidant activities of different fractions of the methanolic extract of A. carambola leaves (MEACL). Methods: The antioxidant activity was investigated using FRAP, and ABTS and DPPH radical-scavenging assays and the inhibitory activity toward pancreatic lipase (PL) and HMG-CoA reductase was assayed in vitro. Acute hyperlipidemia was induced by poloxamer-407 (P-407) in rats and different fractions of MEACL (n-hexane, chloroform, n-butanol, ethyl acetate (EA), water, and chloroform) were orally administered. Cholesterol and triglycerides were determined at 0, 12, 24, and 48 h and LDL-C, vLDL-C, HDL-C, lipid peroxidation (LPO) and antioxidants were assayed after 48 h. The expression of ABCA1, ABCG5, ABCG8, LDL-R, SREBP-1, and SREBP-2 and the activity of HMG-CoA reductase were assayed in the liver of P-407-administered rats treated with the EA fraction. Results: The in vitro data revealed potent radical-scavenging activities of MEACL fractions with the most potent effect showed by the EA fraction that also suppressed the activities of HMG-CoA reductase and PL. In P-407-induced hyperlipidemic rats, all fractions prevented dyslipidemia as shown by the decrease in total cholesterol, triglycerides, LDL-C, vLDL-C and atherogenic index. MEACL and its fractions prevented LPO and boosted GSH, superoxide dismutase, glutathione peroxidase, and catalase in P-407-administered rats. The EA fraction showed more effective anti-hyperlipidemic and antioxidant effects than other fractions and downregulated SREBP-2 while upregulated ABCA1 and LDL-R and ameliorated LPL and HMG-CoA reductase in hyperlipidemic rats. Conclusion: MEACL showed in vitro and in vivo antioxidant activity and the EA fraction significantly ameliorated dyslipidemia in a rat model of P-407-induced acute hyperlipidemia by modulating LPL, PL, HMG-CoA reductase, and cholesterolgenesis-related factors. Therefore, the leaves of A. carambola represent a safe alternative for the star fruit particularly in kidney disease patients, and the EA is the most effective anti-hyperlipidemic and antioxidant fraction

    Inducible clindamycin resistance and nasal carriage rates of Staphylococcus aureus among healthcare workers and community members

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    Background: Nasal carriage of Staphylococcus aureus is becoming an increasing problem among  healthcare workers and community individualsObjectives: To determine the prevalence of methicillin-resistant S. aureus (MRSA) nasal colonization and inducible clindamycin resistance (ICR) of S. aureus among healthcare workers at Soba University Hospital and community members in Khartoum State, Sudan.Methods: Five hundred nasal swabs samples were collected during March 2009 to April 2010. Isolates were identified using conventional laboratory assays and MRSA determined by the disk diffusion method. The D-test was performed for detection of ICR isolates with Clinical Laboratory Standard Institute guidelines.Results: Of the 114 S. aureus isolated, 20.2% represented MRSA. The occurrence of MRSA was  significantly higher among healthcare worker than community individuals [32.7% (18/55) vs. 6.9% (5/59)] (p=0.001). Overall the 114 S. aureus isolates tested for ICR by D-test, 29 (25.4%) yielded inducible resistance. Significantly higher (p=0.026) ICR was detected among MRSA (43.5%) than methicillin-susceptible S. aureus (MSSA) (20.9%).Conclusion: MRSA nasal carriage among healthcare workers needs infection control practice in hospitals to prevent transmission of MRSA. The occurrence of ICR in S. aureus is of a great concern, D- test should be carried out routinely in our hospitals to avoid therapeutic failure.Keywords: S. aureus nasal carriage, healthcare workers, community members, inducible clindamycin resistanc

    Understanding Conditional Associations between ToxCast in Vitro Readouts and the Hepatotoxicity of Compounds Using Rule-Based Methods

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    Current in vitro models for hepatotoxicity commonly suffer from low detection rates due to incomplete coverage of bioactivity space. Additionally, in vivo exposure measures such as Cmax are used for hepatotoxicity screening which are unavailable early on. Here we propose a novel rule-based framework to extract interpretable and biologically meaningful multi-conditional associations to prioritize in vitro endpoints for hepatotoxicity and understand the associated physicochemical conditions. The data used in this study was derived for 673 compounds from 361 ToxCast bioactivity measurements and 29 calculated physicochemical properties against two lowest effective levels (LEL) of rodent hepatotoxicity from ToxRefDB, namely 15mg/kg/day and 500mg/kg/day. In order to achieve 80% coverage of toxic compounds, 35 rules with accuracies ranging from 96% to 73% using 39 unique ToxCast assays are needed at a threshold level of 500mg/kg/day, whereas to describe the same coverage at a threshold of 15mg/kg/day 20 rules with accuracies of between 98% and 81% were needed, comprising 24 unique assays. Despite the 33-fold difference in dose levels, we found relative consistency in the key mechanistic groups in rule clusters, namely i) activities against Cytochrome P, ii) immunological responses, and iii) nuclear receptor activities. Less specific effects, such as oxidative stress and cell cycle arrest, were used more by rules to describe toxicity at the level of 500mg/kg/day. Although the endocrine disruption through nuclear receptor activity formulated an essential cluster of rules, this bioactivity is not covered in four commercial assay setups for hepatotoxicity. Using an external set of 29 drugs with drug-induced liver injury (DILI) labels, we found promiscuity over important assays discriminates between compounds with different levels of liver injury. In vitro-in vivo associations were also improved by incorporating physicochemical properties especially for the potent, 15mg/kg/day toxicity level, as well for assays describing nuclear receptor activity and phenotypic changes. The most frequently used physicochemical properties, predictive for hepatotoxicity in combination with assay activities, are linked to bioavailability, which were the number of rotatable bonds (less than 7) at a of level of 15mg/kg/day, and the number of rings (of less than 3) at level of 500mg/kg/day. In summary, hepatotoxicity cannot very well be captured by single assay endpoints, but better by a combination of bioactivities in relevant assays, with the likelihood of hepatotoxicity increasing with assay promiscuity. Together these findings can be used to prioritize assay combinations which are appropriate to assess potential hepatotoxicity

    Laser and radiofrequency-induced hyperthermia treatment via gold-coated magnetic nanocomposites

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    Alsayed AM Elsherbini1, Mahmoud Saber2, Mohamed Aggag2, Ahmed El-Shahawy2, Hesham AA Shokier11National Institute of Laser Enhanced Science, 2Children's Cancer Hospital, Cairo, EgyptIntroduction: The current radiofrequency ablation technique requires invasive needle placement. On the other hand, most of the common photothermal therapeutic methods are limited by lack of accuracy of targeting. Gold and magnetic nanoparticles offer the potential to heat tumor tissue selectively at the cellular level by noninvasive interaction with laser and radiofrequency.Methods: Gold nanospheres and gold-coated magnetic nanocomposites were used for inducing hyperthermia to treat subcutaneous Ehrlich carcinoma implanted in female mice.Results: In mice treated with gold nanospheres, tumors continued to grow but at a slow rate. In contrast, more than 50% of the tumors treated with gold-coated magnetic nanocomposites completely disappeared.Conclusion: This simple and noninvasive method shows great promise as a technique for selective magnetic photothermal treatment.Keywords: laser, hyperthermia, gold magnetic nanocomposites, Ehrlich carcinom

    Small Molecule Glycomimetics Inhibit Vascular Calcification via c-Met/Notch3/HES1 Signalling

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    © Copyright by the Author(s). Published by Cell Physiol Biochem Press. BACKGROUND/AIMS: Vascular calcification represents a huge clinical problem contributing to adverse cardiovascular events, with no effective treatment currently available. Upregulation of hepatocyte growth factor has been linked with vascular calcification, and thus, represent a potential target in the development of a novel therapeutic strategy. Glycomimetics have been shown to interrupt HGF-receptor signalling, therefore this study investigated the effect of novel glycomimetics on osteogenic signalling and vascular calcification in vitro. METHODS: Primary human vascular smooth muscle cells (HVSMCs) were induced by β-glycerophosphate (β-GP) and treated with 4 glycomimetic compounds (C1-C4). The effect of β-GP and C1-C4 on alkaline phosphatase (ALP), osteogenic markers and c-Met/Notch3/HES1 signalling was determined using colorimetric assays, qRT-PCR and western blotting respectively. RESULTS: C1-C4 significantly attenuated β-GP-induced calcification, as shown by Alizarin Red S staining and calcium content by day 14. In addition, C1-C4 reduced ALP activity and prevented upregulation of the osteogenic markers, BMP-2, Runx2, Msx2 and OPN. Furthermore, β-GP increased c-Met phosphorylation at day 21, an effect ameliorated by C2 and C4 and the c-Met inhibitor, crizotinib. We next interrogated the effects of the Notch inhibitor DAPT and confirmed an inhibition of β-GP up-regulated Notch3 protein by C2, DAPT and crizotinib compared to controls. Hes-1 protein upregulation by β-GP, was also significantly downregulated by C2 and DAPT. GOLD docking analysis identified a potential binding interaction of C1-C4 to HGF which will be investigated further. CONCLUSION: These findings demonstrate that glycomimetics have potent anti-calcification properties acting via HGF/c-Met and Notch signalling

    Berberine mitigates methotrexate-induced oxidative stress and inflammation in the cerebrum of rats

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    Berberine is a natural isoquinoline alkaloid with multiple beneficial therapeutic effects. This study was designed to evaluate the protective effect of berberine against methotrexate (MTX)-induced oxidative stress and inflammation in the brain of rats. Rats received a single intraperitoneal injection of MTX (20 mg/kg) and orally administered 25 mg/kg and 50 mg/kg body weight berberine for 7 days. MTX-induced rats showed significantly increased lipid peroxidation and nitric oxide levels in the cerebrum. Treatment of the MTXinduced rats with berberine produced a significant decrease in cerebral levels of lipid peroxidation and nitric oxide. In addition, berberine induced a significant increase in reduced glutathione, superoxide dismutase, glutathione peroxidase and glutathione-S-transferase in the cerebrum of MTX-induced rats. Rats received MTX showed a significant up-regulation of nuclear factor-kappaB (NF-κB), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1β) expression in the cerebrum, an effect that was significantly reversed following treatment with berberine. In conclusion, berberine protects against MTXinduced neurotoxicity through attenuating oxidative stress and inflammation, and boosting the antioxidant defenses

    Corneal Biomechanical Response Alteration After Scleral Buckling Surgery for Rhegmatogenous Retinal Detachment

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    Purpose: To compare the corneal biomechanics of eyes that underwent scleral buckle (SB) for rhegmatogenous retinal detachment (RRD) with those of fellow eyes (fellow eyes) and to further investigate the effects of SB on intraocular pressure (IOP) values. Design: Retrospective, fellow-eye matched cohort study. Methods: A total of 18 consecutive patients (11 males and 7 females) treated with SB for RRD in 1 eye were enrolled. Goldmann applanation tonometry was used to measure IOP. Biomechanical properties of the cornea were investigated by using the Ocular Response Analyzer (ORA) (Reichert Instruments) for the calculation of corneal resistant factor (CRF), corneal hysteresis, Goldmann-correlated IOP, and corneal-compensated IOP. Customized software was used for analysis of the ORA infrared and pressure signals, and a significance threshold was set to a P value of. 05. Results: Operated eyes (OEs) showed significantly lower values of corneal hysteresis and CRF than fellow eyes (9.0 ± 1.8 vs 10.1 ± 1.8 mm Hg, respectively; P < .001; 10.0 ± 2.2 vs 10.9 ± 2.2 mm Hg; P < .001). GAT was significantly lower than corneal-compensated IOP in OEs (18.1 ± 4.9 vs 19.8 ± 4.8 mm Hg, respectively; P = .022) but not in fellow eyes. The second applanation event (A2) took place earlier in time, and the cornea was moving faster during A2 in the OEs than in the fellow eyes. Conclusions: SB for the treatment of RRD affects corneal biomechanical response, likely due to a less compliant sclera that limits corneal motion and reduces energy dissipation, reflected in a lower corneal hysteresis. This has potentially meaningful clinical implications as the accuracy of the measurement of IOP values may be affected in these eyes
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