The current global concern in the treatment of tuberculosis (TB) is the emergence of resistance to the two most potent drugs namely, isoniazid and rifampicin. Emergence of multidrug resistance tuberculosis (MDR-TB) is now a health problem faced by most of the developing countries as well as developed countries across the globe. MDR-TB is a man-made disease that is caused by improper treatment, inadequate drug supplies, and poor patient supervision. HIV infection and AIDS have been implicated as important cause for this. The review of a published literature suggests that the most powerful predictor of treatment of MDR-TB is a history of treatment of TB. Although the treatment is efficacious, there are also a number of adverse effects caused by drugs used in the treatment of MDR-TB.

Antihistamines are one of the most common drugs that are used extensively in various dermatological and nondermatological conditions. The use of H-1-antihistamines during pregnancy has been very controversial due to possible teratogenic effects of these drugs. None of the antihistamines available today have been categorized as safe during pregnancy. Control studies are available for certain first generation drugs regarding their safety in pregnancy, but the newer agents require further studies to be declared safer in pregnancy. A few drugs are comparatively safer to use in pregnancy than others. Every drug used in pregnancy carries a risk for teratogenicity and careful risk/benefit assessment should be done before prescribing them.

Unwanted pregnancy is a global reproductive health problem. Emergency contraception is defined as the use of drug or device after unprotected or underprotected intercourse to prevent an unwanted pregnancy. 1.5 mg of levonorgestrel as a single dose or in two doses with 12 h apart taken within 72 h of unprotected intercourse is the current gold standard emergency contraception regimen. This method is only effective if used as soon as possible after sexual intercourse and before ovulation. A single dose of 30 mg ulipristal acetate, a novel selective progesterone receptor modulator, has recently been proposed for the emergency contraception use up to 120 h of unprotected intercourse with similar side effect profiles as levonorgestrel. Ulipristal acetate could possibly prevent pregnancy when administered in the advanced follicular phase, even if luteinizing hormone levels have already begun to rise, a time when levonorgestrel is no longer effective in inhibiting ovulation.

Despite of established and effective therapy for epilepsy, 20-25% patients develop therapeutic failure; this encourages finding newer drugs. Novel approaches target receptors which remain unaffected by conventional therapy or inhibit epileptogenesis. AMPA receptor antagonists have shown faster and complete protection compared to diazepam. Protein kinase (PK) plays an important role in the development of epilepsy. PK inhibitors such as K252a, VID-82925, and Herbimycin A have been found effective in inhibition of spread of epileptiform activity and epileptogenesis. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors classified into three groups. Group 1 mGluRs antagonist and Groups 2 and 3 mGluRs agonists inhibited pentylenetetrazole-induced kindled seizures. Combined use of these agents has also shown favorable results. Mammalian target of rapamycin (mTOR) plays a central role in multiple mechanisms of epileptogenesis. mTOR causes transcription, induction of proapoptotic proteins, and autophagy inhibition. Rapamycin was effective in suppression of recurrent seizures as well as in tuberous sclerosis and acute brain injury model. 5% CO ₂ showed potent effects on cortical epileptiform activity and convulsions in animal epilepsy models and in humans with drug-resistant partial epilepsy. It is found to be rapidly acting, safe and cheap, thus it can be a good option in emergency for suppression of seizure. Neurosteroids are considered as fourth generation neuromessengers, they act as positive allosteric modulators of γ:-aminobutyric acid (GABAA) receptors. Clinical trial of ganaxolone, an allopregnanolone analogue, has shown a beneficial role in pharmacoresistant epilepsy. However, most of these drugs are tested in early phases of development and the possible use and safety in epilepsy has to be proven in clinical trials.

Vitamin D insufficiency affects almost 50% of the population worldwide. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. As the number of people with VDD continues to increase, the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research. VDD is very common in all age groups. As few foods contain vitamin D, guidelines recommended supplementation at suggested daily intake and tolerable upper limit levels. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency. Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. In this review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and understand its biology and clinical implications.

The rapidly increasing prevalence of diabetes on a global scale beseeches an urgent need for newer and better treatment options. Our better understanding of the pathophysiology of diabetes has enabled a continual churn out of newer antidiabetic agents with varying modes of action. Sodium-Glucose Transport Proteins-2 inhibitors, dipeptidyl peptidase IV inhibitors, glucagon-like peptide analogues, glucokinase activators, dual peroxisome proliferator-activated receptor agonists, monoclonal antibodies, and dopamine-2 receptor agonists either as monotherapy or combination therapy with the existing oral hypoglycemic agents compound our fight against diabetes. A review of the newer drugs targeting various aspects in the management of diabetes is presented.

Objectives: To investigate the alterations in GABA levels by rolipram in the model of depression. Materials and Methods: The alteration of GABA content by rolipram as a phosphodiesterase enzyme type-4 inhibitor in the frontal cortex (FCx; as a brain region crucial for the control of emotion and cognition) obtained from male mice exposed to chronic mild stress (CMS)-induced anhedonia (the loss of pleasure or lack of sensitivity to pleasure stimuli) was recorded. Results: The results demonstrated the reversal of CMS-induced anhedonia after 3 weeks per os of rolipram in a dose of 0.1 mg/kg/day dissolved in distilled water. Furthermore, rolipram showed a significant reduction in duration of immobility in long-term behavioral changes recorded by the FST. Additionally, there was a significant increase in the GABA content of the FCx of rolipram-treated mice exposed to CMS-induced anhedonia. Conclusions: The present study suggested that GABA levels may be decreased in an animal model of depression and its reversal together with the behaviour improvement by rolipram could support the hypothesis that modification in GABAergic activity has a role in mood disorders. These effects may complement the antidepressant effect of rolipram that is originally mediated via inhibition of phosphodiesterase enzyme type-4 [PDE4] that increases cyclic adenosine monophosphate signalling the pharmacotherapy of depression.

Objective: To study the adherence levels and explore factors impacting them in out-patients on antiretroviral therapy (ART) at the AIDS Prevention Initiative in Nigeria antiretroviral clinic of the Jos University Teaching Hospital. Materials and Methods: We administered a structured questionnaire to 461 patients presenting to the clinic. Adherence was measured using the patient self-report. The association between independent variables and adherence to ART was measured through odd ratios (OR) in the univariate analysis. The best predictors of adherence were determined through multiple logistic regression models with backward elimination. Results: The adherence level was found to be 87.9%. The following factors were found to have strong impact on adherence in the univariate analysis: age (OR 1.04), sex (OR 1.14), employment (OR 1.29), knowledge of HIV (OR 1.11), thrice daily frequency of drug intake (OR 1.68), twice daily frequency (OR 2.18), alcohol nonintake (OR 0.29), knowledge of ARVs (OR 1.23), pill burden (OR 1.20), and HIV status disclosure (OR 1.08). In the multivariate analysis, only age, alcohol nonintake and twice daily, frequency of drug intake affected adherence (P < 0.05). Conclusions: To increase adherence and the effectiveness of ART, there is need to continuously emphasize the use of adherence devices and reminders. Counseling and adherence education should also be emphasized especially for younger patients and those with low educational levels.

Objective: To compare the cardiorenal effects of early versus late cyclosporine (CsA) to sirolimus (SRL) conversion, using a novel animal model that mimics these protocols used in the clinical practice, and focusing on blood pressure, heart rate (HR), biochemical data and heart and kidney lipid peroxidation. Materials and Methods: The study had five groups. Six male Wistar rats in each group were used during a 9-week study protocol: control, CsA (5 mg/kg/day), SRL (1 mg/kg/day); early conversion and late conversion. Cardiorenal evaluation was assessed by biochemical data, blood pressure, HR, and heart and kidney lipid peroxidation. Results: As expected, CsA promoted cardiorenal impairment, viewed by development of hypertension, tachycardia, increased urea, creatine kinase, and glucose levels, as well as heart and kidney oxidative stress. SRL, as expected, promoted less cardiorenal side effects, namely those related with nephrotoxicity. In agreement, both early and late conversions from CsA to SRL produced less side-effects, namely those related to the CsA-induced nephrotoxicity. Conclusions: In our model, both early and late CsA to SRL conversion promoted amelioration of the CsA -induced cardiorenal damage. However, early substitution seems to produce more benefits, in particular due to higher improvement of the cardiac profile.

Introduction: To evaluate the hepatoprotective activity of active phytochemicals, picroliv, curcumin, and ellagic acid in comparison to silymarin in the mice model of carbon tetrachloride (CCl ₄ ) induced liver toxicity. In addition, attempts were made to elucidate their possible mechanism(s) of action. Materials and Methods: Oxidative stress was induced in Swiss albino mice by a single injection (s.c.) of CCl ₄ , 1 ml/kg body weight, diluted with arachis oil at a 1:1 ratio. The phytochemicals were administered once a day for 7& days (p.o.) as pretreatment at two dose levels (50 and 100 mg/kg/day). Results: CCl ₄ -induced hepatotoxicity was manifested by an increase in the activities of liver enzymes (alanine transaminase, P < 0.001, aspartate transaminase, P < 0.001 and alkaline phosphatase, P < 0.001), malondialdehyde (MDA, P < 0.001)) levels and a decrease in activity of reduced glutathione (P < 0.001) and catalase in liver tissues. The histopathological examination of liver sections revealed centrizonal necrosis, fatty changes, and inflammatory reactions. The pretreatment with picroliv, curcumin, and ellagic acid normalized serum aminotransferase activities (P < 0.001), decreased levels of MDA (P < 0.001), improved the antioxidant status, and normalized the hepatic histo-architecture. The restoration of phenobarbitone-induced sleeping time also suggested the normalization of liver cytochrome P450 enzymes. Conclusion: This study supports the use of these active phytochemicals against toxic liver injury, which may act by preventing lipid peroxidation, augmenting the antioxidant defense system or by regenerating the hepatocytes.

Objective: To determine the association between altered thyroid hormones and insulin resistance (IR). Materials and Methods: Eight euthyroid (EU), eight hypothyroid (HO), and eight hyperthyroid (HR) patients with no past medical history were studied in this cross-sectional study at the Care Institute of Medical Sciences, Ahmedabad, India, The fasting blood sample were analyzed for thyroid stimulating hormone (TSH), lipid profile, insulin, and glucose. Homeostatic model assessment (HOMA) was calculated for assessing IR. Results: HOMA values were significantly higher in HR and HO groups as compared to the EU group (P < 0.05). Insulin levels were also found to be significantly increased in HR and HO groups as compared to the EU group (P < 0.05). Cholesterol, triglycerides (TG), and low density lipoprotein (LDL) were significantly raised in HO as compared to EU and HR groups (P < 0.05) whereas high density lipoprotein levels (HDL) were lower. HOMA and insulin were found to be positively correlated with TSH in HO and negatively in HR. Conclusion: Thyroid disorder, including both hypo- and hyper have been associated with IR due to various mechanisms such as altered insulin secretion and lipid levels. IR was comparable in patients with both HO and HR. Although HO and HR constitute an IR state, more studies need to be done in order to clarify the underlying pathogenic mechanism. Thus, an altered thyroid state can lead to IR leading to glucose-related disorder such as diabetes dyslipidemia.

Objective: To investigate the effects of Celastrus paniculatus seed oil in preventing the onset of chronic aluminum induced cortico-hippocampal neurodegeneration and oxidative stress. Materials and Methods: An animal model of senile dementia of Alzheimer's type was produced by administering aluminum as aluminum chloride (4.2 mg/kg) intraperitoneally to male Wistar rats for 60 days and results compared to untreated control. Neurobehavioral investigations of Morris water maze tests, passive avoidance test, rotarod test and biochemical estimations of acetylcholineterase, malondialdehyde, glucose-6-phosphate dehydrogenase, superoxide dismutase, and hemoglobin in blood were performed fortnightly which gauged the extent of global oxidative stress and progressive neural damage. Findings were fortified by the above enzyme assays and histology of brain at necropsy. Prophylactic oral C. paniculatus in two doses 0.5 ml and 1 ml, were given to animals and the results were analyzed in comparison to a similar rodent model with standard drug donepezil (0.5 mg/kg) intraperitoneally. Results: C. paniculatus showed a significant prevention in onset of aluminum induced neural insult and overall systemic oxidative stress which was corroborated by the enlisted neurobehavioral, biochemical, and histological evidence. Conclusion: C. paniculatus is a putative decelerator of Al-mediated Alzheimer's like pathobiology.

Blood pressure (BP) is one of the vital parameters used to assess the cardiovascular functions of a mammal. BP is commonly recorded using invasive, noninvasive, and radio telemetry methods, but invasive blood pressure (IBP) recording is considered the gold standard. IBP provides a direct indication of the effect of the investigational products on the circulatory system. Recording the IBP in rodents is an essential part of the preliminary screening of any product to determine its effect on the cardiovascular system. The present article describes the measurement of the IBP in Wistar rats/Sprague Dawley rats.

Gynecomastia is very rare during antituberculosis chemotherapy. We describe a 38-year-old male patient who developed a painful gynecomastia following second-line drug therapy for multidrug-resistant pulmonary tuberculosis. Gynecomastia disappeared after stopping the ethionamide. A published literature on antituberculosis-induced gynecomastia is also briefly discussed.

Docetaxel is an important chemotherapeutic agent used in the management of many solid tumors. The most important side effect of this drug is myelosupression. We report a case of carcinoma breast that developed severe hand-foot syndrome at 75 mg/m ² doses of docetaxel. The exact mechanism of this side effect in not known. All the physicians using this drug must be aware of this side effect.

Carbamazepine (CBZ) is frequently used for epilepsy and various psychiatric illnesses. It is known for its dermatological side effects which may range from mild rash to life-threatening reactions as Stevens Johnson syndrome or toxic epidermal necrolysis. We hereby report a rare case of 17-year-old woman suffering from generalized tonic clonic epilepsy with comorbid bipolar affective disorder, who was initially treated with sodium valproate with partial improvement. After 19 days of addition of CBZ to the therapy, the patient developed erythema multiforme major with >60% skin involvement and oral, conjunctival, intestinal, and vaginal mucosal involvement.