Antimicrobial and toxicological studies on fruit pulp of Citrullus colocynthis L.

The methanolic extract of dried fruit pulp of Citrullus colocyn this (Cucurbitaceae) has been studied with respect to antimicrobial and toxicological properties. The antimicrobial profile was investigated against thirty bacterial isolates (10 Gram +ve and 20 Gram-ve) and five fungal species. None of the bacterial or fungal culture used in the study showed sensitivity against the extract. Acute toxicity studies carried out in Albino mice NMRI indicated the highly toxic nature of the colocynth. A very significant decrease in body weight of test animals was noted at P<0.05. The LD(50) was calculated as 1000mg/kg body weight. Within four days of experimentation mortality was 100%. Histopathological studies confirmed the toxic nature of extract. Gross changes in histology of Heart, Liver and Kidneys were noted. Section of spleen did not exhibit any abnormality.

Photodegradation and stabilization of betamethasone-17 valerate in aqueous/organic solvents and topical formulations.

The effects of solvent [acetonitrile, methanol, and acetonitrile/water mixture (20:80, v/v)], buffer concentration (phosphate buffer, pH 7.5), ionic strength and commonly employed adjuvants on the photodegradation of betamethasone-17 valerate in cream and gel formulations have been studied on exposure to UV light (300-400 nm). A validated high-performance liquid chromatography method has been used to determine the parent compound and its photodegraded products. The photodegradation data in the studied solvents showed greater decomposition of the drug in solvents with a lower dielectric constant. A comparatively higher rate of photodegradation was observed in the cream formulation compared to that for the gel formulation. The kinetic treatment of the photodegradation data revealed that the degradation of the drug follows first-order kinetics and the apparent first-order rate constants for the photodegradation reactions, in the media studied, range from 1.62 to 11.30×10(-3) min(-1). The values of the rate constants decrease with increasing phosphate concentration and ionic strength which could be due to the deactivation of the excited state and radical quenching. The second-order rate constant (k') for the phosphate ion-inhibited reactions at pH 7.5 has been found to be 5.22×10(-2) M(-1) s(-1). An effective photostabilization of the drug has been achieved in cream and gel formulations with titanium dioxide (33.5-42.5%), vanillin (21.6-28.7%), and butyl hydroxytoluene (18.2-21.6%).

Pharmacokinetic study of cephradine in Pakistani healthy male volunteers.

To observe and discuss the difference in the pharmacokinetics of cephradine in Pakistani population with the reported data of other ethnic origins. A Single group pharmacokinetic study was conducted having six healthy male volunteers of 20-24 years of age. Blood samples were collected at appropriate times up to 7 hours. Plasma concentrations of cephradine was determined by HPLC technique and pharmacokinetic parameters were determined by both compartmental and noncompartmental methods using Kinetica ver 4.4.1 and Winnonlin ver 5.01. Peak plasma concentration was 11.49+/-1.73 microg/ ml achieved at 0.76+/-0.12 hr, after the administration of 250 mg cephradine to fasting volunteers. Area under the serum concentration-time curve was found to be 16.4+/-1.71 g.hr/ ml. Absorption, distribution, disposition and elimination half lives were calculated as 0.183 +/- 0.038 hr, 0.248 +/- 0.143 hr, 2.126 +/- 0.341 hr and 0.441+/-0.193 hr respectively where as the volume of central compartment and total body clearance were found to be 9.65+/-3.78 L and 15.4+/-1.89 L/hr. The plasma concentration time curves showed the absorption rate constant was 3.968 +/- 0.05 hr(-1), disposition rate constant was 0.333+/-0.05 hr(-1), distribution rate constant was 3.64+/-2.18 hr(-1) and elimination rate constant was 1.738+/-0.468 hr(-1). The value of micro-constants i.e. K(12) (central to peripheral compartment) and K(21) (peripheral to central compartment) were found to be 1.529+/- 1.499 hr(-1) and 0.704 +/- 0.44 hr(-1) respectively, where as MRT and AUMC were calculated as 2.04+/-0.09 hr and 35.92+/-1.86 hr(2) microg/ ml. The findings showed that the results of Pakistani subjects are slightly different when compared with the reported data of other ethnic origin.

Antimicrobial activity of Penicillins in common paediatric infections.

Pediatric bacterial infections are very rapidly growing in developing countries. Bacterial resistance to antimicrobial agents is a serious problem in the treatment of Pediatric bacterial infection. One of the most effective ways to control antibiotic resistance, is the development of surveillance programs. For this purpose isolates were collected from paediatric wards of different hospitals. The result shows that isolates were highly resistant against majority of selected antibiotics with increase in the MIC's. In Penicillin group, the most effective agent is Amoxicillin and Clavulanic acid, more than 90% isolates of Staphylococcus aureus were susceptible while other agents, as Cloxacillin, Ampicillin and Amoxicillin alone shows moderate activity against Staphylococcus aureus and Escherichia coli.

Comparative antimicrobial evaluation of Cephalosporins and Quinolones in common paediatric infections.

More than 90% of world's children are born each year in the developing world. Each year 12.9 million children die. Twenty eight percent of death are caused by pneumonia, 23% by diarrheal disease and 16% by vaccine-preventable diseases. Thirty-five thousand die each day, most from common and preventable problems. Health and illness are the result of a complex dynamic of environmental, social, political and economic factors. Bacterial resistance to antimicrobial agents is a continuing serious problem in the treatment of infections. Although this problem was recognized shortly after the commercial introduction of antimicrobial agents, it means that resistance is now emerging at a more rapid rate than ever before. To start with, during the present study an effort has been made to accomplish this task, 84 clinical isolates of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were collected from different hospitals in Karachi. An in vitro study of these isolates was carried out by Agar dilution method using eleven antimicrobial agents and their combination (Lorian, 1991). Among Cephalosporins, third generation Cephalosporin, Cefotaxime was highly effective against Gram positive and Gram negative bacteria. Cefotaxime was active against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. 1.19% isolates of Staphylococcus aureus, 19% isolates of Escherichia coli and 10% isolates of Pseudomonas aeruginosa were resistant against Cefotaxime. In Quinolone group, Ofloxacin was highly active against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Whereas 28% isolates of Staphylococcus aureus, 26% isolates of Escherichia coli and 11% isolates of Pseudomonas aeruginosa were resistant to Ofloxacin. Twenty six percent isolates of Staphylococcus aureus and 58% isolates Escherichia coli were resistant against Ciprofloxacin.

Resistance pattern of different aminoglycosides against Gram positive and Gram negative clinical isolates of Karachi.

Microbial resistance to majority of the available antimicrobial agent is a serious and global problem. Due to heavy and discriminate usage of antibiotics, high prevalence of drug-resistant bacteria in the indigenous fecal flora, poor standards of sanitation, lack of education and prevalence of malnutrition. This problem is at its extreme in developing countries like Pakistan. For this various Aminoglycosides were tested against different Gram positive and Gram negative isolates. The results showed that these isolates were resistant against most of these antibiotics with increase in MIC's. In Aminoglycoside group Tobramycin was the most effective agent against Staph. aureus and E. coli with MIC90s of 1 microg/ml and 2 microg/ml, while against Klebsiella and P. aeruginosa its activity was moderate to low. Amikacin showed highest activity against P. aeruginosa, E. coli and Klebsiella species with MIC90s of 4 microg/ml and 8 microg/ml. Kanamycin and Streptomycin were not active against the tested isolates.