Oxidative stress and alternation of renin-angiotensin system has been implicated in the pathophysiology of various cardio vascular, endocrine including mood and anxiety disorders. The present study evaluated the role of irbesartan in stress induced different models of depression. Mice were treated with irbesartan (40 mg/kg), fluoxetine (25 mg/kg) alone in combination orally. Drugs treatment started after 2 weeks from the beginning of the unpredictable mild stress (UCMS) protocol. Behavioural tests were performed on week 6, at least 24 h after the last treatment. Modified forced swim test (MFST), tail suspension test (TST) and open field test (OFT) were used followed by antioxidant markers and 5-HT levels determination. Irbesartan increased swimming, climbing and decreased immobility times in MFST, decrease immobility time in TST. Irbesartan also increased no. of field crossings; rearings and also increased time spent in the centre of OFT. Thus, antidepressant like activity in UCMS mice was observed. Combination of irbesartan with fluoxetine showed potentiating effect of behavioural parameters in all animal models. Combination groups also showed antioxidant effects and elevated the 5-HT levels in UCMS mice. Chronic administration of Irbesartan exerted antidepressant like effect, reduced oxidative stress and elevated brain 5-HT levels.

Objectives: To determine the frequency of Protein C, Protein S (PC & PS), antithrombin deficiency (AT III) and Factor V Leiden mutation (FVL) as a cause of thrombophilia in the patients with venous thromboembolism (VTE) and cerebrovascular accident (CVA). Methods: It was an observational study conducted at Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, Pakistan. All patients referred for thrombophilia screening from July 2009 to June 2012 were screened. Patients with evidence of VTE or CVA were screened for PC & PS, AT III deficiency, and FVL. Results: Total 404 patients of age between 1-71 years mean 33 ± 14 with male to female ratio of 2.4:1 had evidence of thrombophilia. Two hundred eighteen (54%) patients presented with CVA, 116 (29%) with deep vein thrombosis (DVT), 42 (10.5%) with pulmonary embolism (PE), and 28 (7.5%) with portal or mesenteric vein thrombosis (PV). Protein C & S deficiency was detected in 35/404 (8.7%), ATIII in 9/404 (2%), and FVL in 25/173 patients (14.5%). The findings were suggestive of a significant association of FVL mutation for developing DVT (OR=11.0, 95% C I 4.6-26.3), CVA (OR=5.7, 95% C I 2.1-15.1), and PV (OR=5.4, 95% C I 1.3-21.9). PC & PS deficiency was a significant risk factor for developing PE (OR=3, 95% C I 0.8-11.4). Conclusion: FVL mutation and Protein C & S are the leading causes of thrombophilia with strong association of Factor V Leiden mutation as risk for developing DVT.

XmnI polymorphism in homozygous/compound heterozygous BT group is 13%. The most common genotype associated with XmnI polymorphism was IVSI-5/IVSI-5.

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Background: Infections caused by typhoidal salmonellae are an important public health concern in Pakistan. Inappropriate and injudicious use of fluoroquinolones has reduced their efficacy due to development of high level resistance. <br />Aim: To ascertain the current susceptibility pattern of typhoidal salmonellae thus guiding the physicians for better management of typhoid patients.<br />Materials and Methods: A study was conducted at our institution from January 2012 through December 2013 to investigate current susceptibility pattern of typhoidal salmonellae. <br />Results: Out of 200 isolates, 107 (53.5%) were identified as <em>Salmonella</em> Typhi and 93 (46.5%) as <em>Salmonella</em> Paratyphi A. Sensitivities of <em>Salmonella</em> Typhi were as follows: ampicillin (48.6%), chloramphenicol (45.8%), co-trimoxazole (40.1%), ciprofloxacin (11.2%). Sensitivities of <em>Salmonella</em> Paratyphi A were: ampicillin (80.6%), chloramphenicol (89.2%), co-trimoxazole (90.3%), and ciprofloxacin (16.1%). No resistance was detected against third generation cephalosporins. <br />Conclusions: Typhoidal salmonellae are still entirely susceptible to third generation cephalosporins in our setting. Marked rise in resistance to fluoroquinolones has reduced their empirical usage. Sensitivity of <em>Salmonella</em> Paratyphi A to conventional antityphoid drugs was encouraging.