Attenuation of tamoxifen-induced hepatotoxicity by taurine in mice

BACKGROUND: One of the most attractive approaches to disease prevention involves the use of natural antioxidants to protect tissue against toxic injury. We investigated the modulatory effects of exogenously administered taurine on the toxicity of the anticancer drug tamoxifen with special reference to protection against disruption of drug metabolizing and antioxidant enzymes in Swiss albino mice. METHODS: Male Swiss albino mice were divided into 4 groups. The extent of lipid peroxidation was evaluated in terms of thiobarbituric acid reactive substances formed. The following assays were performed in the hepatic tissue (a) antioxidant enzymes such as superoxide dismutase and catalase, (b) cytochrome P450 content, (c) glutathione-metabolizing enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose 6-phosphate dehydrogenase, and (d) low molecular weight antioxidants (reduced glutathione, ascorbic acid) and protein carbonyl content. RESULTS: Tamoxifen induced lipid peroxidation, protein carbonyl content and inhibited the enzymes of antioxidant defense system. It was also observed that the activities of antioxidant enzymes and glutathione-metabolizing enzymes were considerably stabilized in mice pretreated with taurine. CONCLUSION: Taurine protects the integrity of the hepatic tissue by stabilizing the reactive oxygen species mediated lipid peroxidation and protein carbonyl formation. Additionally taurine may prove to be efficacious as an antioxidant in tamoxifen-induced hepatotoxicity.     

T-cell sensitisation to hepatitis B virus surface antigens

The present study was conducted to explore the immunity to hepatitis B surface antigens (HBsAg) of ad and ay subtypes at the cellular level among adult individuals. Peripheral blood mononuclear cells (PBMCs) obtained from acute hepatitis B virus (HBV) infected patients, chronic HBV infected patients, recovered subjects from HBV infection and uninfected vaccinated controls were stimulated with HBsAg ad and HBsAg ay subtypes in vitro. Stimulated PBMCs were incubated in CO(2) for production of interferon-gamma (IFN-gamma), which was measured from the supernatant of cultured PBMCs by an in-house ELISA technique. The mean +/- SE of IFN-gamma levels produced by PBMCs in response to HBsAg ad among the acute, chronic, recovered and control groups were 282.5+/-134.51 pg/ml, 307.45+/-94.84 pg/ml, 915.62+/-170.80 pg/ml and 511.67+/-161.22 pg/ml respectively, while on stimulation by HBsAg ay, the levels were 246.25+/-103.50 pg/ml, 374.70+/-104.02 pg/ml, 1040 +/-140.76 pg/ml and 465.83+/-166.26 pg/ml respectively among the above mentioned groups. The results of this study showed that PBMCs were non-responsive to stimulation by both HBsAg ad and HBsAg ay subtypes in acute and chronic patients with HBV infection. The recovered group responded significantly to both subtypes of HBsAg and the control group did not. The study indicates that although the patients with acute and chronic HBV infection showed weak or no IFN-gamma response to the HBsAg, subjects showed strong IFN-gamma response to the surface antigens on recovery from HBV infection.     

Interleukin‐ 28B: a prognostic marker in interferon based therapy of chronic HCV patients of the Pakistan with variable treatment response

Unfortunately Pakistan carries one of the world's highest burdens of chronic hepatitis along with mortality due to liver failure and hepatocellular carcinoma. Scientists after extensive research have come up with this outcome that host genetics play a vital role in dictating the type of treatment response produced by the patients. In 2009, a genome wide association study (GWAS) revealed that genetic variants in close proximity to the IL28B (IFNL3) gene predicted greater likelihood of achieving sustained virological response (SVR) following treatment with pegylated IFN‐alpha (peg INF‐α) and ribavirin. IL28B (rs12979860 and rs8099917) single nucleotide polymorphisms (SNPs) have been recently found among the Pakistani population associated with response to chronic HCV infection INF‐α + ribavirin therapy. Therefore, this study was aimed to investigate the IL‐28B protein levels in the HCV infected patients. The findings showed that the serum IL28B protein level was higher in HCV infected patients as compared to healthy controls (7.743 ± 1.519 pg/mL versus 1.600 ± 0.06054 [mean ± SEM], p < 0.05). When the chronic hepatitis C (CHC) patients were further categorized into SVR and NR (non‐responders) on the basis of treatment outcomes, the mean IL28B protein level was higher in NRs (15.54 ± 3.609) than SVRs (4.259 ± 0.3405). Thus, there was a significant correlation between IL28B protein level in varied treatment response (p < 0.05). However, the findings can lead us to propose that IL28B could be used as a prognostic marker. It can help the clinicians to take better pre‐informed decisions whether to take combinational therapy of peg IFN ± ribavirin or not. This will in turn prove beneficial for the patient by saving patients’ health, treatment cost and undesirable treatment side effects.     

Catechin prevents tamoxifen-induced oxidative stress and biochemical perturbations in mice

Natural antioxidants like catechin are now known to have a modulatory role on physiological functions and biotransformation reactions involved in the detoxification process, thereby affording protection from toxic metabolic actions of xenobiotics. Reactive oxygen intermediates have been demonstrated to play an etiological role in anticancer drug-induced toxicity. This study was performed to explore the modulatory and protective effect of catechin on the toxicity of an anticancer drug, tamoxifen (TAM) with special reference to protection against disruption of glutathione metabolizing and antioxidant enzymes. TAM treatment resulted in a significant increase in the lipid peroxidation (LPO), H(2)O(2) generation and protein carbonyl (PC) contents in the liver and kidney as compared to controls while catechin+TAM-treated group showed significant decrease in LPO levels, H(2)O(2) generation and PC contents in liver and kidney when compared with TAM-treated group. Non-enzymatic antioxidants like reduced glutathione (GSH) and low molecular antioxidants like ascorbic acid (AsA) also showed normalcy due to exogenous catechin administration. Catechin pre-treatment showed restoration in the level of cytochrome P450 (CYP) content and in the activities of glutathione metabolizing enzymes, viz., glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) and other antioxidant enzymes such as, glucose-6-phosphate dehydrogenase (G6-PD), catalase (CAT) and superoxide dismutase (SOD) in both liver and kidney when compared to TAM-treated animals. The results of the study show that catechin supplementation might be helpful in abrogation of TAM toxicity during chemotherapy. Additionally, it makes it a prophylactic and preventive agent of anticancer drug-induced oxidative stress.     

Poor Oral Health and Coronary Artery Disease: A Case‐Control Study

Background: There is insufficient research on the relationship of oral health and coronary artery disease (CAD) from developing countries, such as Pakistan. This study observes the status of oral health in the CAD population. Methods: A case‐control study was conducted on 145 cases and 145 controls. Otherwise healthy patients with CAD (cases) and individuals free from previous/current history of CAD (controls), having ≥14 remaining teeth, were examined for oral health status through missing teeth, plaque index (PI), and community periodontal index (CPI). Student t test, χ² test, and multivariate regression analysis were applied at significance level of 95% (P ≤0.05) to compare study parameters between cases and controls. Results: A significant difference between cases and controls was observed in this study sample with respect to missing teeth (P = 0.027) and periodontal parameters of PI and CPI (P <0.001). Cases were observed with significantly higher scores of PI (2 and 3) and CPI (3 and 4) compared with controls. Prevalence of periodontal parameters was observed to be higher in cases than controls at subgroup‐level (sex and age group) analysis. A significant odds ratio (OR), unadjusted, between CAD and periodontal indicators of PI (mild to severe plaque/no plaque: OR = 5.04, 95% confidence interval [95% CI] = 2.24 to 11.36) and CPI (healthy/poor periodontal status: OR = 4.59, 95% CI = 1.81 to 11.61) scores was noted; cases were at odds of 1.20 (95% CI = 0.93 to 15.68, P = 0.017) for having poor oral health after adjusting age, sex, and education. Conclusion: Poor oral health was significantly associated with CAD in this study sample matched for sociodemographic characteristics.     

Double cortex syndrome (subcortical band heterotopia): A case report

Double cortex syndrome is an uncommon familial syndrome with X-linked dominant inheritance and most commonly presents with developmental delay and seizures. We present a case of a 14-year-old girl who came to neurology department of the hospital with severe generalized tonic-clonic fits and loss of consciousness. The mother of child gave history of uneventful antenatal period and labor. There was history of immediate cry and normal APGAR score. She was achieving milestones normally until at the age of 3 years when she suffered decline in her speech and vision. She had problems with learning with lack of concentration during her schooling. Physical examination was also unremarkable. Her lab values including complete blood count, serum calcium, and arterial blood gas tests, all were within normal limits. Electroencephalogram showed significant changes suggestive of epilepsy. Magnetic resonance imaging of brain showed continuous band of gray matter that was located deep and paralleling the cortex in both cerebral hemispheres suggestive of band heterotopia or double cortex syndrome. She was discharged and prescribed antiepileptics; and was advised regular outpatient follow-up.