N-phenyl and N-benzyl substituted succinimides: Preclinical evaluation for their antihypertensive effect and underlying mechanism.

The study was designed to investigate the antihypertensive potential of 2-(2, 5-dioxo-1-phenylpyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (Comp-1) and 2-(1-benzyl-2,5-dioxopyrrolidin-3-yl)-3-(4-isopropylphenyl)-2-methylpropanal (Succ-5) in rats. The study results showed that, just like nifedipine (the standard reference drug), the test compounds, Comp-1 (at doses of 15 and 20 mg/kg) and Succ-5 (at a dose of 20 mg/kg) had significant antihypertensive effect against deoxycorticosterone acetate-salted rats. The test compounds maintained the level of cardiac markers troponin I and creatinine kinase myocardial bands (CK-MB) in serum, and modulate the oxidative stress markers Glutathione s-transferase (GST) activity, reduced glutathione (GSH), catalase levels, and lipid peroxidation (LPO). These compounds also reduced the expression of inflammatory markers, including cyclooxygenase-2 (COX-2) and tumor necrosis factor alpha (TNF-α) in heart tissues. Furthermore, in the ex-vivo study, the test substances relaxed the contractions induced by phenylephrine (PE) and potassium (K+). Vasodilation was endothelium-independent because the test substances showed nearly the same effect in aortic rings with intact endothelium, denuded endothelium, and with L-NAME pretreatment. The test compounds shifted the calcium curve to the right, i.e., contraction was inhibited and decreased the maximal response. This study demonstrated the antihypertensive, anti-inflammatory, antioxidant, and vasodilate effects of the test compounds. In addition, the results supported the phenomenon of calcium channel blockades responsible for vasodilation.

Using Culture Sensitivity Reports to Optimize Antimicrobial Therapy: Findings and Implications of Antimicrobial Stewardship Activity in a Hospital in Pakistan.

Background: There are concerns with inappropriate prescribing of antibiotics in hospitals especially broad spectrum in Pakistan and the subsequent impact on antimicrobial resistance rates. One recognized way to reduce inappropriate prescribing is for empiric therapy to be adjusted according to the result of culture sensitivity reports. Objective: Using culture sensitivity reports to optimize antibiotic prescribing in a teaching hospital in Pakistan. Methods: A retrospective observational study was undertaken in Ghurki Trust Teaching Hospital. A total of 465 positive cultures were taken from patients during the study period (May 2018 and December 2018). The results of pathogen identification and susceptibility testing from patient-infected sites were assessed. Additional data was collected from the patient's medical file. This included demographic data, sample type, causative microbe, antimicrobial treatment, and whether empiric or definitive treatment as well as medicine costs. Antimicrobial data was assessed using World Health Organization's Defined Daily Dose methodology. Results: A total of 497 isolates were detected from the 465 patient samples as 32 patients had polymicrobes, which included 309 g-negative rods and 188 g-positive cocci. Out of 497 isolates, the most common Gram-positive pathogen isolated was Staphylococcus aureus (Methicillin-sensitive Staphylococcus aureus) (125) (25.1%) and the most common Gram-negative pathogen was Escherichia coli (140) (28.1%). Most of the gram-negative isolates were found to be resistant to ampicillin and co-amoxiclav. Most of the Acinetobacter baumannii isolates were resistant to carbapenems. Gram-positive bacteria showed the maximum sensitivity to linezolid and vancomycin. The most widely used antibiotics for empiric therapy were cefoperazone plus sulbactam, ceftriaxone, amikacin, vancomycin, and metronidazole whereas high use of linezolid, clindamycin, meropenem, and piperacillin + tazobactam was seen in definitive treatment. Empiric therapy was adjusted in 220 (71.1%) cases of Gram-negative infections and 134 (71.2%) cases of Gram-positive infections. Compared with empiric therapy, there was a 13.8% reduction in the number of antibiotics in definitive treatment. The average cost of antibiotics in definitive treatment was less than seen with empiric treatment (8.2%) and the length of hospitalization also decreased. Conclusions: Culture sensitivity reports helped reduced antibiotic utilization and costs as well as helped select the most appropriate treatment. We also found an urgent need for implementing antimicrobial stewardship programs in hospitals and the development of hospital antibiotic guidelines to reduce unnecessary prescribing of broad-spectrum antibiotics.

Evaluation of prevalence of different types of cancer and its chemotherapy in various ethnic groups of Pakistan: A retrospective study

The objective of the study was to evaluate different types of cancer and its chemotherapy in various ethnic groups of Pakistan. Ethnic groups includes, Pukhtoons, Punjabis, Sindhis, Muhajirs, Siraikis, Memoons, Hazaras, Hindkos, Baltis, Gilgitis, Kashmiris, and Afghanis. The data was collected from well reputed hospitals located in the different provinces of Pakistan. The collected data was taken from 15 hospitals where around 8500 patients visited during 2010 to 2017. From the visited patients, 8356 were analyzed for their ethnicity, age and sex while, 144 patients (male 77 and female 67) were excluded from analysis due to incomplete information or loss of follow-up. Among 8356 patients, 3762 were male (45%) whereas, 4594 were female (55%). The chemotherapy was carried out as per National Comprehensive Cancer Network guidelines (NCCN- guidelines). The most common five prevalent cancer among these ethnic groups were Head and Neck, Blood, Respiratory, Genito-urinary and Breast cancer. The most common cancer in female was breast cancer while, head and neck cancer was more prevalent in male. It can be concluded that the prevalence of cancer in Pakistan is very alarming, which may be due to lack of awareness, illiteracy, lack of national cancer control programs, and economics issues.