Anesthesia protocol for ear surgery in Wistar rats(animal research)

Objective:To formulate an anesthesia protocol for safe and satisfactory anesthesia for ear surgery in rats.Methods:The rats were anesthetized with xylazine(10 mg/kg body weight)and keta-mine at doses of 80,50,40,and 30 mg/kg body weight or with isoflurane anesthesia(2%-3.5%in 100%oxygen;maintenance dose 1.5%-3.5%).The anesthesia induction,surgery,and recovery time were recorded.Results:In total,17 rats were induced by varying doses of ketamine-xylazine and 28 rats with isoflurane.Mean induction time with ketamine-xylazine was 6±2.9 min compared with 3.8±1.1 min with isoflurane.Mean recovery time with ketamine-xylazine was 142.6±49.3 min compared with 4.1±1.2 min with isoflurane.A mortal-ity of 4 animals after developing dyspnea was recorded with ketamine-xylazine.Conclusion:Isoflurane anesthesia offers appropriate induction and recovery times and low mortality rates for the surgeries performed.Isoflurane anesthesia offers reli-able results for ear surgery in rats.However,more equipment and technical skills are needed.

Genetically modified mouse models for the study of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is associated with obesity,insulin resistance,and type 2 diabetes.NAFLD represents a large spectrum of diseases ranging from(1) fatty liver(hepatic steatosis);(2) steatosis with inflammation and necrosis;to(3) cirrhosis.The animal models to study NAFLD/nonalcoholic steatohepatitis(NASH) are extremely useful,as there are still many events to be elucidated in the pathology of NASH.The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis,but these remain incompletely understood.The different mouse models can be classified in two large groups.The first one includes genetically modified(transgenic or knockout) mice that spontaneously develop liver disease,and the second one includes mice that acquire the disease after dietary or pharmacological manipulation.Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex,genetically modified animal models may be a key for the treatment of NAFLD.Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans.To date,no single animal model has encompassed the full spectrum of human disease progression,but they can imitate particular characteristics of human disease.Therefore,it is important that the researchers choose the appropriate animal model.This review discusses various genetically modified animal models developed and used in research on NAFLD.

Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer

BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.

Hepatotoxic Alterations Induced by Subchronic Exposure of Rats to Formulated Fenvalerate (20% EC) by Nose Only Inhalation

Objective Fenvalerate (20% EC) is a synthetic pyrethroid, which is commonly used in India by farmers for the protection of many food and vegetable crops against a wide variety of insects. However, its inhalation toxicity data is very limited in the literature due to the fact that the exposure levels associated with these effects were usually not reported. Hence, inhalation exposure was carried out to investigate the hepatotoxic effects. Method Adult male rats were exposed to fen for 4 h/day, 5 days a week for 90 days by using Flow Past Nose Only Inhalation Chamber. Sham treated control rats were exposed to compressed air in the inhalation chamber for the same period. Results The results indicated hepatomegaly, increased activities of serum clinical enzymes (indicative of liver damage/dysfunction) along with pronounced histopathological damage of liver. Conclusion The hepatotoxic potential of formulated Fen (20% EC) in rats exposed by nose only inhalation is being reported for the first time and warrant adequate safety measures for human beings exposed to this insecticide, particularly by inhalation route.