Effect of methionine on hepatotoxicity due to co-administration of gentamicin and indomethacin in rats

Synchronous administration of gentamicin and indomethacin is, sometimes, a necessity. However, the effect of this treatment on the liver and the possible effect of methionine on their hepatotoxicity have not been studied well. This study was performed on 42 male Sprague Dawley rats to elucidate the effect of combined treatment with gentamicin and indomethacin and the potential effect of methionine on their hepatotoxicity. Rats were divided into six equal groups randomly and were injected with normal saline, gentamicin, indomethacin, gentamicin and indomethacin, methionine, and a combination of three above-mentioned treatments for 14?days. Twenty-four hours after the last injection, blood samples were taken for measuring AST and ALT. Histopathologic and biochemical evaluations have shown severe hyperemia in the indomethacin group but no significant changes in AST or ALT. Gentamicin-administered rats have shown mild hyperemia, capillarization of sinusoids, deformed and acidophilic hepatocytes, and apoptosis and infiltration of mononuclear cells in the parenchyma and portal area. These changes were associated with elevated levels of AST and ALT. Co-administration of gentamicin and indomethacin has resulted in the development of various lesions in liver structure and enhanced concentrations of AST and ALT, while administration of methionine with the two other agents ameliorated these changes as evidenced by a mild hyperemia observed in hepatic tissue and no significant changes in AST and ALT. Methionine-treated rats, as rats injected by normal saline, have shown no pathologic lesion and no liver enzyme activity augmentation. The obtained results revealed that gentamicin may aggravate indomethacin hepatotoxicity, and methionine managed to ameliorate this effect.     

Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

Self-emulsifying drug delivery system (SEDDS) is an isotropic mixture of lipid, surfactant and co-surfactant, which forms a fine emulsion when comes in contact of an aqueous medium with mild agitation. SEDDS is considered as a potential platform for oral delivery of hydrophobic drug in order to overcome their poor and irregular bioavailability challenges. In spite of fewer advantages like improved solubility of drug, bypassing lymphatic transport etc., SEDDS faces different controversial issues such as the use of appropriate terminology (self-microemulsifying drug delivery system; SMEDDS or self-nanoemulsifying drug delivery system; SNEDDS), presence of high amount of surfactant, correlation of in vitro model to in vivo studies, lack of human volunteer study and effect of conversion of SEDDS to final administrable dosage form on pharmacokinetic behavior of the drug. In this review, potential issues or questions on SEDDS are identified and summarized from the pharmacokinetic point of view. Primarily this review includes the conflict between the influences of droplet size, variation in correlation between in vitro lipolysis or ex-vivo intestinal permeation and pharmacokinetic parameters, variation in in vivo results of solid and liquid SEDDS, and potential challenges or limitation of pharmacokinetic studies on human volunteers with orally administered SEDDS. In the past decades, hundreds of in vivo studies on SEDDS have been published. In the present study, only the relevant article on in vivo pharmacokinetic studies with orally administered SEDDS published in past 5–6 years are analyzed for an up to date compilation.     

Expression analysis of vitamin D receptor-associated lncRNAs in epileptic patients

Vitamin D has been vastly acknowledged as a neuroactive steroid controlling neurodevelopment. As it exerts its functions through activation of vitamin D receptor (VDR), several studies have assessed the role of VDR in brain function. More recently, a number of long non-coding RNAs (lncRNAs) have been recognized that alter expression of VDR. In the current study, we evaluated expression of four VDR-related lncRNAs (LINC00511, LINC00346, SNHG6 and SNHG16) in peripheral blood of 40 epileptic patients and 39 healthy subjects using quantitative real time PCR method. The relative expression levels of SNHG16 and LINC00511 were higher in epileptic patients compared with healthy subjects. For SNHG16, the difference was only significant between male patients and male controls, while LINC00511 had the opposite pattern. The results of Quantile regression model showed significant associations between SNHG6 and SNHG16 expressions and gender (P values of 0.027 and 0.009 respectively). Significant correlations were detected between expression levels of SNHG6 and SNHG16 (r?=?0.32, P =?0.004), SNHG6 and LINC00346 (r?=?0.37, P =?0.001), SNHG16 and LINC00346 (r?=?0.30, P =?0.007) as well as SNHG16 and LINC00511 (r?=?0.29, P =?0.009). Expression of LINC00346 was inversely correlated with vitamin D levels only in male epileptic patients (r?=??0.58, P =?0.011). Expression of SNHG6 was correlated with vitamin D levels in male controls but no other subgroups (r?=?0.51, P =?0.044). Based on the results of ROC curve analysis, SNHG16 had the diagnostic power of 0.86 in male subjects. Taken together, the current study provides evidences for dys-regulation of VDR-related lncRNAs in epileptic patients. The clinical significance of these finding should be explored in future studies.

     

Level of hyperlipidemia in blood donors: A correlative study in North Indian population

BackgroundHyperlipidemia can be caused by abnormal elevation of lipids and lipoproteins in the blood. This increased can lead to heart disease. Risks which can be controlled include alcohol intake, physical activity, smoking, high blood pressure and genetic factors. Markers of increased cardiovascular risk appear to be lower in regular blood donor compared with single time donors as reflected by significantly lower total cholesterol and LDL levels. And it has been thought that there will be a direct relationship between lower risks of Heart diseases with repeated blood donation.AimThe aim of the present study is to determine the effect of blood donation on single time and repeat donors by assessing their lipid levels and their family history of heart diseases.Material & methodsThis cross-sectional study was carried out on (n = 80) random blood donors from the department of Transfusion Medicine KGMU.ResultsA significant correlation was found amongst hyperlipidemic level in single time donor & repeat donors and in donors with family history of heart diseases (p < 0.05). A positive association was found between hyperlipidemia with donor's weight (p < 0.05).ConclusionScreening random donor platelets for hyperlipidemia and correlating the condition with other donor criteria like family history of heart diseases, types of donors, donors weight age and gender will help in making the patients safe as well as the donor deferral criteria more stringent to improve the quality of blood supply and will enable blood bankers to supply safe blood and improve the guidelines for blood safety.     

Disparities in treatment and survival between African American and White women with vaginal cancer

Objective

The study aims to compare the difference in treatment and survival between White (W) and African American (AA) patients with vaginal cancer (VC).

Methods

Patients with a diagnosis of invasive vaginal cancer were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007 and were divided into White (W) and African American (AA) subgroups. Student's t test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed.

Results

A total of 2675 patients met the inclusion criteria, with histologic distribution of squamous cell carcinoma (SCC; 2190, 82%) and adenocarcinoma (AC; 485, 18%); 2294 (85.8%) were W, and 381 (14.2%) were AA. Median age was 69 for W and 65 for AA (p < 0.001). SCC and AC were equally distributed between W and AA. Advanced stage disease (FIGO III and IV) was more prominent in AA compared with W (30.4% vs. 23.1%, p = 0.019). Radiation therapy was utilized equally in both racial groups; however, surgical treatment alone or combined with radiation therapy was more frequent in W compared with AA (27.7% vs. 17.5%, p < 0.001).The 5-year survival was 45% in W and 38.6% in AA (p = 0.008). In multivariate analysis, AA had significantly poorer survival compared with Whites when controlling for age, histology, stage, grade and treatment modality (HR 1.2, 95% CI 1.1-1.4, p = 0.007).

Conclusions

African American women with vaginal cancer were more likely to present, at a younger age, advanced stage and less likely to receive surgical treatment. Our data suggests that AA race is an independent predictor of poor survival in vaginal cancer.