Loss of pancreatic β-cell function is a hallmark of Type-II diabetes mellitus (DM). It is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Recently, United Kingdom Prospective Diabetes Study reported that Type-II DM is a progressive disorder. Although, DM can be treated initially by monotherapy with oral agent; eventually, it may require multiple drugs. Additionally, insulin therapy is needed in many patients to achieve glycemic control. Pharmacological approaches are unsatisfactory in improving the consequences of insulin resistance. Single therapeutic approach in the treatment of Type-II DM is unsuccessful and usually a combination therapy is adopted. Increased understanding of biochemical, cellular and pathological alterations in Type-II DM has provided new insight in the management of Type-II DM. Knowledge of underlying mechanisms of Type-II DM development is essential for the exploration of novel therapeutic targets. Present review provides an insight into therapeutic targets of Type-II DM and their role in the development of insulin resistance. An overview of important signaling pathways and mechanisms in Type-II DM is provided for the better understanding of disease pathology. This review includes case studies of drugs that are withdrawn from the market. The experience gathered from previous studies and knowledge of Type-II DM pathways can guide the anti-diabetic drug development toward the discovery of clinically viable drugs that are useful in Type-II DM.

Context: Chronic kidney disease is an increasing health problem worldwide and in its final stage (stage V) can only be treated by renal replacement therapy, mostly hemodialysis. Hemodialysis has a major influence on the everyday life of patients and many patients report dissatisfaction with treatment. Objectives: To study the clinical profile of patients with ESRD undergoing hemodialysis and to find out possible etiology which may have led to ESRD in these patients? Settings and Design: This is a prospective, observational study carried out in a tertiary care hospital. Methods and Material: 50 patients, older than 15 years who were on maintenance hemodialysis in this hospital on outpatient basis for more than 3 months were selected for the study. Detailed clinical history, general and systemic examination of all patients was performed. Two manifestations pertaining to each system was taken for study. Statistical Analysis Used: Descriptive as well as inferential statistics were used to analyze the data. Results: Most patients were in the age group of 51-60 with male: female ratio of 1.77:1. Diabetes and hypertension were most common causes for ESRD. Anemia and electrolyte disturbances like hyperkalemia along with hypocalcemia, hyperphosphatemia and hyperuricemia have common associations with ESRD. Conclusions: Lack of health awareness and lack of regular health checkup in general population is one of the culprit factor for progression of renal disease. Health awareness in general population may decrease the incidence of ESRD or postpone the development of ESRD.

Aim:To classify the patients as per the International Classification of Headache disorders 3 rd edition Beta version. To study the demographic details and clinical profile. To study the trigger factors in migraine patients. To study the importance of family history is headache patients. Materials & Methods: The study was a cross sectional observational study of 300 patients at outpatient clinic tertiary health care center, over a period of two years. Patients diagnosed with primary headache were studied with help of an exhaustive questionnaire which covered the relevant details. Results: Our study had 158 migraines (MG), 137 Tension Type Headache (TTH) and 5 Trigeminal Autonomic Cephalgia (TAC) patients. Females are more affected, 1:2.9 in TTH and 1:1.5 in MG. Mean age for MG was 33.37 and for TTH were 36.11. Majority (46-48%) were employed, followed by housewives (43-38%) and students (9-13%) among both the groups. TTH patients had frequency of headache more patients than migraine patients. Family history was positive in 36% in MG and 14% in TTH patients. TTH had dull aching, holocranial pain with pericranial tenderness; whereas migraine had throbbing unilateral pain. Aura was seen only in 21% of MG patients; retinal (67%) being most common. Associated symptoms like nausea, phonophobia, photophobia were seen in 80% of MG patients. Trigger factors on history were present in 64%, which increased to 85% on showing detail list. Most common triggers were climatic, followed by travel, stress and sleep related. Females had hormonal, smell and emotional stress as more common TF. Conclusion: Migraine is most common primary headache presenting in clinics. With predominance in females TTH attacks are more frequent than migraine. TTH showed features like dull aching, pressure like and holocranial pain whereas migraine has throbbing and unilateral pain. Pericranial tenderness is more in TTH patients whereas migraine has associated vasomotor symptoms. It is important to have detail list of all Trigger factors for Migraine patients, so that they can avoid them and prevent their attacks, thus reducing analgesic use. Family history has more influence in migraine patients compared to TTH.headache and associated features occur without any exogenous cause. These conditions may have a complex interplay of genetic, developmental, and environmental risk factors. They are also called idiopathic by definition. Common primary headaches include migraine, tensiontype, and cluster. Neurological examinations and imaging

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Carbamazepine is a first-line antiepileptic drug (AED) used for the treatment of partial and tonic-clonic seizures. We conducted an open label, balanced, randomized, two-treatment, two-sequence, four-period, single oral dose, full-replicate crossover study to assess and compare the  bioequivalence of  test  product  Carbamazepine extended release tablets USP 400 mg with reference  product Tegretol®-XR 400 mg (Carbamazepine extended release tablets), respectively in  healthy subjects under fasting and fed conditions. Blood samples were collected pre-dose and at regular intervals post-dose up to 240.00 hours. The plasma concentration was analyzed by a validated LC-MS/MS method and the reference-scaled and the unscaled procedure was used to determine bioequivalence for the pharmacokinetics parameters, Cmax, AUC0–t, AUC0-inf, Tmax, T½, Kel and AUC extrapolated was calculated. The results showed that the geometric mean ratios of Cmax, AUC0–t and AUC0-inf were 113.04%, 108.33% and 108.15% respectively, in the fasting conditions and 113.99%, 110.13% and 111.41%, respectively, in the fed conditions and the 90% confidence intervals were all within the range of 80.00% to 125.00%. It can be concluded from the result that the test product Carbamazepine extended release tablets based on osmotic release system (OROS) are bioequivalent to the reference product Tegretol®-XR tablets. Keywords:  Bioequivalence, Carbamazepine, Sodium Channel Modulators and Epilepsy