Mukhtiar Hassan

Metal complexes of tosyl sulfonamides: design, X-ray structure, biological activities and molecular docking studies

The present study reports the synthesis of Zn(II) complexes of tosyl sulfonamide derivatives obtained by the reaction of tosyl chloride with L-amino acids. The ligands and their complexes were characterized by IR, 1H and 13C-NMR, GC-MS, elemental analysis and X-ray crystallography in the case of NA3. All compounds were screened for their carbonic anhydrase inhibitory activities. Results demonstrated that complexes are stronger inhibitors of carbonic anhydrase compared to their parent ligands, which warrants further development of organometallics as active carbonic anhydrase inhibitors. Cytotoxicity assays on lung carcinoma (H-157) and kidney fibroblast (BHK-21) cancer cells demonstrated that compounds were potent anticancer agents. Additionally, the complexes were screened against promastigote forms of Leishmania major and found to be significant antileishmanial agents. Molecular docking studies were performed against bCA II enzymes to rationalize the inhibitory properties of these compounds. The identified inhibitors showed promise for the design of interesting pharmacological agents.

CCHF virus variants in Pakistan and Afghanistan: Emerging diversity and epidemiology

BACKGROUND Crimean Congo hemorrhagic fever (CCHF) has been reported from more than 30 countries in Africa, Asia, Eastern Europe and Middle East. The disease is considered endemic in Pakistan and neighboring countries like Iran and Afghanistan. OBJECTIVES This study aimed to explore the genetic diversity of CCHF virus (CCHFV) detected in Pakistan and Afghanistan based on analysis of partial S-segment sequences. STUDY DESIGN During 2011, one hundred samples satisfying the CCHF case definition were tested by (ELISA) and RT-PCR for detection of IgM antibodies and viral RNA, respectively. Phylogenetic analysis was carried out on partial S-segment nucleotide sequences using MEGA 5.0. RESULTS Out of one hundred collected during 2011, 49 (49%) were positive for CCHF either by ELISA/RT-PCR or both. The mean age of the CCHFV positive cases was 30.32 years (range 18-56 years) and overall mortality rate was 20.4%. All CCHF virus isolates from this study clustered with strains previously reported from Pakistan, Iran and Afghanistan within the Asia-1 genogroup. Four distinct sub-clades were found circulating within Asia-1 genogroup. Six CCHFV strains found in Pakistan and Afghanistan grouped into a new sub-clade-D. CONCLUSIONS Data from this study shows that endemic foci of CCHFV span the international border between Pakistan and Afghanistan with genetically diverse variants circulating in this region. Our findings emphasize to establish a laboratory based surveillance program and devise health policy measures to control CCHF infection especially in Baluchistan.

DNA landmarks for genetic diversity assessment in tea genotypes using RAPD markers

Tea (Camellia sinensis) is one of the most important non-alcoholic beverages of the world. Natural genetic diversity in tea has been reduced due to continue selection in favor of desirable traits. The present study was conducted to estimate genetic diversity in tea genotypes cultivated in Pakistan using 20 randomly amplified polymorphic DNA (RAPD) primers. 75 tea accessions from 13 tea genotypes were analyzed. Genetic distance estimates ranged from 0-100% showing high level of diversity among screened genotypes. Unweighted pair group method using arithmetic averages (UPGMA) based cluster analyses of RAPD data clustered all the genotypes into five main groups which showed mixed grouping profile of the samples. However, samples from different plants of particular genotypes were segregated into independent sub-clusters. Broad and narrow leaved genotypes were accommodated in separate sub-clusters. Similarly, samples from narrow leaved genotypes collected from different sites were grouped in different main clusters reflecting the geographical origins of tea samples. Results obtained confirm that RAPD methodology is practically applicable for evaluation of genetic diversity and relationship in tea genotypes.

Antibacterial spectrum of traditionally used medicinal plants of Hazara, Pakistan

The use of medicinal plants for treatment of infections is an old age practice. On the basis of this important practice, this study was initiated to evaluate the antibacterial effects of medicinal plants, commonly used by the community of Hazara region of Pakistan. Antibacterial spectrum of traditionally used medicinal plants was determined by disc diffusion method under incubation period of 24 to 48 h at 37°C. Four medicinal plants were tested against the different species of human pathogenic bacteria. It was observed that Incarvillea emodi have good activity against Proteus and significantly active against Staphylococcus . Vernonia anthelmintica revealed significant activity against Staphylococcus and Proteus . However, Pseudomonas is resistant to Adiantum capilus-veneries and this plant is negligibly active against other tested microorganism. Mentha longifolia is significantly active against Proteus , while negligibly active against other tested microorganisms. Escherichia coli is however, resistant to M longifolia . Keywords: Biological activity, medicinal plants, Incarvillea emodi , Vernonia anthelmintica , Adiantum capilus-veneries , Mentha longifolia , Hazara, Pakistan

Prevalence of Extended Spectrum β-Lactamase and Antimicrobial Susceptibility Pattern of Clinical Isolates of Pseudomonas from Patients of Khyber Pakhtunkhwa, Pakistan.

Majority of gram negative pathogenic bacteria are responsible for extended spectrum β-lactamases (ESBLs) production, which show resistance to some newer generation of antibiotics. The study was aimed at evaluating the prevalence of ESBL and antibiotic susceptibility pattern of Pseudomonas isolates collected during 2010 to 2014 from tertiary care hospitals of Peshawar, Pakistan. Out of 3450 samples, 334 Pseudomonas spp. isolates comprised of 232 indoor and 102 outdoor patients were obtained from different specimens and their susceptibility pattern was determined against 20 antibiotics. Antimicrobial susceptibility testing was carried out using the Kirby-Bauer agar diffusion method and ESBL production was detected by Synergy Disc Diffusion technique. The mean age group of the patients was 29.9 + 9.15 years. Meronem showed best activity (91.02%) from class carbapenem, β-lactam and β-lactamase inhibitors exhibited 69.16% activity, and doxycycline had a diminished activity (10.18%) to Pseudomonas spp. Outdoor isolates were more resistant than the indoor and during the course of the study the sensitivity rate of antibiotics was gradually reducing. ESBL production was observed in 44.32% while the remaining was non-ESBL. The moderate active antibiotics were amikacin (50.7%), SCF (51.4%), TZP (52.7%), and MXF (54.1%) among ESBL producing isolates. Lack of antibiotic policy, irrational uses (3GCs particularly), and the emergence of antibiotic resistant organisms in hospitals may be causes of high antibiotic resistance.

STRUCTURAL, SURFACE MORPHOLOGICAL AND MAGNETIC STUDIES OF Zn1−xFexS (x=0.00–0.10) DILUTED MAGNETIC SEMICONDUCTORS GROWN BY CO-PRECIPITATION METHOD

We have fabricated Zn1−xFexS (x=0.00, 0.02, 0.04, 0.06, 0.08 and 0.10) diluted magnetic semiconductors using co-precipitation method. X-ray diffraction patterns depict that Zn1−xFexS appears as a dominant phase with cubic zinc blende structure and nanoscale crystallite size. In addition, a secondary phase of rhombohedral ZnS also appears; however, no additional phase arises that primarily belongs to Fe dopant. Using Debye–Scherrer relation, the crystallite size is found to be in the range of 20–27nm, which is in good agreement with the crystallite size calculated using the Williamson–Hall (WH) plot method. The appearance of secondary phase provoked to study the residual strain using Stokes–Wilson equation, which is nearly consistent to that observed using WH plot method. The surface morphology, revealed using scanning electron microscopy, depicts non-uniform surface structure with a variety of grains and void dimensions. Hysteresis loops measured for Zn1−xFexS at room temperature (RT) illustrate a paramagnetic behavior at higher fields; however, small ferromagnetic behavior is evident due to the small openings of the measured hysteresis loops around the origin. The measured RT ferromagnetism reveals the potential spintronic device applications of the studied diluted magnetic semiconductors.

Maternal and fetal blood lead concentrations under non-occupational lead exposure and associated factors in Pakistan

This study in selected Pakistani populations was conducted to determine the blood lead levels (BLL) in mothers and their developing fetuses. Associated factors were correlated with the maternal BLL. Blood samples from 113 pregnant women and their umbilical cords were examined for BLL and cord blood lead levels through a graphite furnace-attached atomic absorption spectrophotometer. A structured questionnaire was also used to obtain sociodemographic and obstetric data based on basic demographic data, reproductive history, hemoglobin levels, gestational age, parity, mode of delivery, maternal and baby weight, drinking water, menarche age, blood pressure, lead (Pb)-containing eye liner use, smoking, and nutritional status. In order to assess the strength of the relationship between different parameters, Pearsons coefficient correlation was utilized and their significance was determined by applying the t-test. Data demonstrated that the maternal BLL were always higher than the recommended concentrations of 10 µg/dl and many factors contributed towards such results. Drinking water seemed to affect the Pb concentration as women using spring water had relatively higher BLL. The calcium concentration in pregnant women and their fetuses ranged from 9 to 13 mg/dl. Majority of the pregnant women were undergraduates with 12 years of education (equivalent to high school in the United States). Evidence indicates that the avoidance of Pb intake and its associated factors in the study area will diminish risk to newborns.

915 STRATIFICATION OF RISK FACTORS FOR NEPHROPATHY IN HYPERTENSIVE DIABETICS

Objectives: Significant proportion of diabetics develop nephropathy in time and hypertension is considered as an adverse influencing factor.The aim was to identify risk factors related to possible deterioration in renal function among Bangladeshi type 2 diabetic hypertensive (DH) subjects. Method: Diabetic subjects with normal renal function (estimated GFR ≥60 ml/min and urinary albumin <30 mg/day) were included in this cross sectional study. Hypertension was taken as BP ≥140/90mmHg when untreated or taking ≥2 antihypertensives. Results: In DH group 342 and another 496 normotensive diabetic (DM) as control group were included. The comparisons between 2 groups respectively showed systolic BP 130 ± 14 vs. 118 ± 11 and diastolic BP 80 ± 7 vs. 76 ± 6, mmHg; (p < 0.001). The diabetes duration was 8 ± 5 vs. 8 ± 4 yrs, HbA1c 8.1 ± 1.8 vs. 7.1 ± 1.3, %; Serum creatinine (SCr) 0.9 ± 0.1 vs. 0.9 ± 0.2, mg/dl and LDL 103 ± 35 vs. 99 ± 37, mg/dl; (P =NS) were similar. The differences in 2 groups, though mostly clinically less significant, were for age 55 ± 8 vs. 53 ± 8 yrs, (p < 0.001); BMI 25 ± 4 vs. 24 ± 2 kg/m2, (p < 0.03); 24hr urinary albumin (Uralb) 10.9 ± 6.4 vs. 9.6 ± 6.4 mg/day (p < 0.01) and estimated GFR 80 ± 20 vs. 84 ± 21 ml/ming/1.73m2, (p < 0.004). Bivariate correlations showed only age had a negative association with SCr, Uralb and eGFR. Further stratification showed around 65% from both DH and DM groups was in the lower range of eGFR (60-90 ml/min).When DH group was compared for eGFR above and below 90 ml/min (33 vs. 67%), no difference was seen for most of the clinical or laboratory parameters (systolic 129 ± 12 vs. 130 ± 14 & diastolic BP 80 ± 7 vs. 79 ± 7, mmHg; and SCr 0.7 ± 0.1 vs. 0.9 ± 0.1, mg/dl; p = NS) Conclusion: It is found that majority of type 2 diabetics with hypertension had lower normal renal function which could only be identified by estimating GFR. Both groups of high and low renal function had similar traditional clinical and laboratory parameters. Additional tools are needed to stratify which of the hypertensives are more at risk for developing nephropathy.