http://localhost:80/xmlui/handle/123456789/14281 2026-04-23T01:51:01Z http://localhost:80/xmlui/handle/123456789/15143 Title: Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers Authors: Fayyaz, Amtul; Khan, Junaid Ali; Ashraf, Muhammad Mudassar; Akhter, Naheed; Aslam, Bilal; Khalid, Muhammad Fiaz; Altaf, Sidra; Naseer, Rana Dawood; Akram, Muhammad; Shah, Syed Muhammad Ali; Khadam, Muhammad Waqas; Tahir, Imtiaz Mahmood Abstract: Aim of present study was to investigate the pharmacokinetic behavior of Montelukast in the healthy male volunteers under indigenous conditions. One tablet of montelukast 10 mg was administered in each subject and blood at different time intervals. Concentration of montelukast in plasma samples was analyzed by high performance liquid chromatography method to calculate pharmacokinetic parameters. The plasma concentration of montelukast was in the range of 1.31-1.76µg/mL at 0.5-12 hours with Cmax value of 1.59±0.16µg/mL at 3.71±0.64 hours. These values of plasma drug concentrations were above the minimum effective concentration of montelukast during the entire study hours. Absorption and elimination half-lives of the montelukast were evaluated as 2.52±0.54 hours and 2.63±0.35 hours, respectively. The volume of distribution and total body clearance of montelukast were investigated as 0.34±0.01 L/kg and 0.01±0.00 L/hr/kg, respectively. The pharmacokinetic parameters i.e. Cmax, AUC, t1/2, Vd and ClB of montelukast calculated in present study were found different as compared to that of the previous literature values which was due to genetic and environmental variation. 2017-11-18T00:00:00Z http://localhost:80/xmlui/handle/123456789/15142 Title: Notch1 signaling activation protected myocardium against hypoxia injury via reducing programmed cell death Authors: Hu, Yongjun; Zheng, Zhaofen; Pan, Hongwei; Peng, Jianqiang; Luo, Yangping; Cui, Bo; Zhong, Xin Abstract: Programmed cell death plays an important role in cardio protection, and Notch1 was an important factor related to programmed cell death. The role of Notch1 on ischemia myocardium remains unclear.H9C2 myocardial cells were cultured with routine medium, transfected with Notch1 over expression plasmid, Notch1-siRNA-overexpression plasmid and vehicle plasmid for further hypoxic experiment. Condition of hypoxic experiment was 1% oxygen centration and culturing for 12hours, then the cell proliferation activity and apoptosis rate was assessed by MTS kit and flow cytometry, respectively. The expressions of Caspase-3, Caspase-9 and Bcl-2 were determined by RT-qPCR and Western Blot, respectively. Compared with normoxia treatment, hypoxia could decrease H9C2 cell proliferation activity as well as Bcl-2 mRNA expression, and increase cell apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression. Notch1 activation could increase proliferation activity as well as Bcl-2 mRNA expression, while decrease apoptosis rate as well as Caspase-3 and Caspase-9 mRNA expression. Compared with Notch1 activation H9C2 cells, the opposite effect on programmed cell death was observed in cells with Notch1-siRNA-overexpression plasmid. Targeted activation of Notch1 gene to reduce hypoxia-induced programmed cell death in myocardial cells via up-regulating the expression of Caspase-3 and Caspase-9 and inhibiting the expression of Bcl-2. 2017-11-17T00:00:00Z http://localhost:80/xmlui/handle/123456789/15141 Title: Dizocilpine induced psychosis-like behavior in rats: A possible animal model with full spectrum of schizophrenia Authors: Shahzad, Sidrah; Ahmad, Saara; Madiha, Syeda; Khaliq, Saima; Liaquat, Laraib; Sadir, Sadia; Rafiq, Sahar; Tabassum, Saiqa; Batool, Zehra; Haider, Saida Abstract: Schizophrenia (SZ) is categorized as neuropsychiatric disorder with reduced lifespan and significant impairments in social and vocational functioning. One of the best proposed pharmacological animal models is dizocilpine, as it can mimic the full spectrum of schizophrenic disorder including positive and negative symptoms along with cognitive deficits. Dizocilpine is N-methyl-D-aspartate (NMDA) receptor antagonist known to induce hyperlocomotion and stereotyped behavior in rodents. Present study was designed to develop an animal model of SZ via intraperitoneal administration of dizocilpine in rats (100-150g) at a dose of 0.3 mg/kg for eight days. For the evaluation of positive symptoms, hyperlocomotor behavior was monitored. Negative symptoms were assessed by sucrose preference test (SPT) and social interaction test (SIT). Moreover, Cognitive deficits were evaluated by novel object recognition test (NORT). After behavioral assessments animals were decapitated for further evaluation of biochemical and neurochemical estimations. Present findings revealed that dizocilpine injected rats exhibited significant hyperlocomotor behavior, depressive symptoms and cognitive deficits. Results are further strengthened with a marked increase in lipid per oxidation (LPO) in brain and a decline in reduced glutathione (GSH) levels. Biogenic amine levels (Dopamine, DA; 5-hydroxytryptamine, 5-HT) were also significantly increased and decreased respectively. Thus, present findings suggest that dizocilpine can be used as one of the best drug to develop psychosis-like symptoms in rats and to develop an animal model following a short-term study. 2017-11-16T00:00:00Z http://localhost:80/xmlui/handle/123456789/15139 Title: MRSA: Prevalence and susceptibility pattern in health care setups of Karachi Authors: Siddiqui, Tuba; Muhammad, Iyad Naeem; Khan, Muhammad Naseem; Naz, Shazia; Bashir, Lubna; Sarosh, Nosheen; Masood, Rida; Ali, Aatka; Fatima, Sakina; Naqvi, Talat Abstract: This assessment aims to determine the prevalence of methicillin resistance and multidrug resistance (MDR) among the clinical isolates of Staphylococcus aureus and antimicrobial susceptibility profile of methicillin resistant Staphylococcus aureus (MRSA) to the frequently prescribed antibiotics in Karachi. Isolates of MRSA, recovered from various clinical samples were included in this prospective, cross-sectional study from Jan 2015 to June 2017. Agar diffusion method was employed according to the protocols of Clinical Laboratory Standards Institute. Out of total 346 S.aureus strains, the frequency rate of MRSA was 52 % (n = 180). MRSA infection was found higher among the age group 21-30 years i.e. 30% (n=54), followed by 20 % (n=36) in 31-40 years. Frequency of MRSA percentage in male and female was and 70 % and 30 % respectively. MRSA was more frequently observed in blood 20 % (n=36). MRSA showed high resistance (100 %) to Oxacillin and Cefoxitin while 25% Vancomycin resistant S. aureus (VRSA) isolates and 25% Teicoplanin resistance were also reported. MRSA exhibited 16% resistance to Minocycline. It was concluded that MRSA pose a challenging threat to public health in Karachi. In addition, MDR should be periodically checked to avoid treatment failure. 2017-11-15T00:00:00Z