Interactions of androgens,green tea catechins and the antiandrogen flutamide with the external glucose-binding site of the human erythrocyte glucose transporter GLUT1

This study investigates the effects of androgens, the antiandrogen flutamide and green tea catechins on glucose transport inhibition in human erythrocytes. These effects may relate to the antidiabetogenic effects of green tea. Testosterone, 4-androstene-3,17-dione, dehydroepiandrosterone (DHEA) and DHEA-3-acetate inhibit glucose exit from human erythrocytes with half-maximal inhibitions (Ki) of 39.2+/-8.9, 29.6+/-3.7, 48.1+/-10.2 and 4.8+/-0.98 microM, respectively. The antiandrogen flutamide competitively relieves these inhibitions and of phloretin. Dehydrotestosterone has no effect on glucose transport, indicating the differences between androgen interaction with GLUT1 and human androgen receptor (hAR). Green tea catechins also inhibit glucose exit from erythrocytes. Epicatechin 3-gallate (ECG) has a Ki ECG of 0.14+/-0.01 microM, and epigallocatechin 3-gallate (EGCG) has a Ki EGCG of 0.97+/-0.13 microM. Flutamide reverses these effects. Androgen-screening tests show that the green tea catechins do not act genomically. The high affinities of ECG and EGCG for GLUT1 indicate that this might be their physiological site of action. There are sequence homologies between GLUT1 and the ligand-binding domain (LBD) of hAR containing the amino-acid triads Arg 126, Thr 30 and Asn 288, and Arg 126, Thr 30 and Asn 29, with similar 3D topology to the polar groups binding 3-keto and 17-beta OH steroid groups in hAR LBD. These triads are appropriately sited for competitive inhibition of glucose import at the external opening of the hydrophilic pore traversing GLUT1.     

Effect of reactor retention on the spread of brucellosis in Jersey cattle and buffalo herds

The rate of spread of bovine brucellosis was investigated in buffalo and Jersey cattle herds maintained at a Livestock Research station in Pakistan. Reactor animals (identified by conventional serological tests) were either retained or culled because of advanced age or poor productivity. Reactors were housed, managed and fed separately from the rest of the herds. The initial seroprevalence of brucellosis among both the Jersey cattle and the buffalo tested was 21.4%, the difference being statistically insignificant (p = 0.218). For 34 months, the spread of brucellosis was limited to 25 new reactors in the 334 cows and 33 in the 442 buffaloes. The mean attack rate was 7.5% for both herds during the test intervals. Trend analysis of proportions positive at each testing revealed a significant decrease in the percentages observed at the first testing. The management practice of segregation offered some advantage in reducing the spread of brucellosis to negative animals. However, an epidemiological study covering a large number of herds would be required to identify risk factors responsible for perpetuating the disease.     

Acoustic and temporal analysis of speech: A potential biomarker for schizophrenia

Currently, there are no established objective biomarkers for the diagnosis or monitoring of schizophrenia. It has been previously reported that there are notable qualitative differences in the speech of schizophrenics. The objective of this study was to determine whether a quantitative acoustic and temporal analysis of speech may be a potential biomarker for schizophrenia.In this study, 39 schizophrenic patients and 18 controls were digitally recorded reading aloud an emotionally neutral text passage from a children's story. Temporal, energy and vocal pitch features were automatically extracted from the recordings. A classifier based on linear discriminant analysis was employed to differentiate between controls and schizophrenic subjects.Processing the recordings with the algorithm developed demonstrated that it is possible to differentiate schizophrenic patients and controls with a classification accuracy of 79.4% (specificity = 83.6%, sensitivity = 75.2%) based on speech pause related parameters extracted from recordings carried out in standard office (non-studio) environments.Acoustic and temporal analysis of speech may represent a potential tool for the objective analysis in schizophrenia.     

巴基斯坦海德拉巴地区连续性斜视17例手术治疗临床观察(英文)

目的:观察接受斜视手术的连续性斜视患者的临床过程和治疗效果。方法:连续性斜视患者(<45岁)分为两组:其中第1组为内斜视患者;第2组为外斜视患者。我们使用棱镜屈光度(PD)来测量患者的偏斜角,对第一次手术后的患者在随访期间(6mo内)进行保守疗法。同时选择随访6mo后偏斜角仍超过15PD的斜视患者进行再次手术。本实验所有参与对象均进行了强制性检查。所有二次手术患者均在全身麻醉下进行,并于术后3,15d;3,6mo进行追踪随访。结果:在整个研究期间有28.8%的患者发展成为连续性斜视。所有斜视患者主视眼(固视眼)的二次手术均在一次手术后6～9mo内进行。经过二次手术干预后,在随访期间两组患者均获得了很好的治疗效果,同时并未出现过矫的趋势。结论:在二次手术过程中我们需谨慎肌肉矫正以避免日后过矫。     

Cataract formation is prevented by administration of verapamil to diabetic rats

The purpose of the present study was to examine the effects on cataractogenesis of daily sc administration of the Ca2+ antagonist drug verapamil to diabetic rats. Streptozotocin-induced diabetic rats were given verapamil half-way through the 8-week experimental period or during the full 8 weeks of diabetes. Verapamil administration had no effect on the high blood glucose values, low circulating insulin levels, or elevated triglyceride and cholesterol concentrations in the diabetic rats. Untreated diabetic rats had a 90% incidence of cataracts. Four weeks of verapamil administration reduced this incidence to 41%, and a full 8 weeks of drug treatment further lowered the incidence to 20%. Diltiazem, another Ca2+ antagonist, lowered the incidence of cataracts in the diabetic rats to a similar extent. Verapamil administration to the diabetic animals also partially protected against the presence of retinal microangiopathy in the diabetic animals. Lenticular hydration and lipid accumulation were only indirectly related to cataractogenesis in the diabetic rats and its protection by verapamil treatment. Lenticular electrolyte imbalance, particularly Ca2+, in the diabetic animals was closely correlated with cataract formation, and verapamil significantly reduced the alterations in these ion concentrations. The present results demonstrate the efficacy of verapamil as a protective agent against cataractogenesis and some retinal damage in diabetic animals. Most importantly, this occurs in the absence of any change in the glycemic status of the diabetic animals. The findings strongly support a role for lenticular Ca2+ imbalance in cataract development in diabetes and provide initial evidence to suggest its clinical use in the diabetic population at risk for blindness.     

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti‐IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free‐breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre‐clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra‐short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti‐IL4Rα‐conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers’ colocalizations with the inflammatory sites in the lung of ovalbumin‐challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd.