Association of Virulence Genes with Antibiotic Resistance in Pakistani Uropathogenic E. coli Isolates.

BACKGROUND: Escherichia coli various strains can cause alarmingly serious infections. Countries like Pakistan harbour the class of bacteria with one of the highest rates of resistance, but very little has been done to explore their genetic pool. OBJECTIVES: This study was designed to find out the frequency of virulence genes of Uropathogenic E. coli and their association with antibiotic resistance along with the evolutionary adaptation of the selected gene through the phylogenetic tree. METHODS: Isolates from 120 urinary tract infected patients were collected. Antibiotic sensitivity was detected by the disk diffusion method and DNA extraction was done by the boiling lysis method followed by PCR-based detection of virulence genes. The final results were analysed using the chi-square test. RESULTS: The isolates were found to be least susceptible to nalidixic acid, followed by ampicillin, cotrimoxazole, cefotaxime, ciprofloxacin, aztreonam, amoxicillin, gentamycin, nitrofurantoin and imipenem. The iucC was the most common virulence gene among the resistant isolates. About 86% of the collected samples were found to be multi-drug resistant. Statistical analysis revealed a significant association between the iucC gene and resistance to ampicillin (P=0.03) and amoxicillin (P=0.04), and also between fimH and resistance to aztreonam (P=0.03). CONCLUSION: This study unravels the uncharted virulence genes of UPEC in our community for the very first time. We report a high frequency of the iucC and fimH virulence genes. This, along with their positive association with resistance to beta-lactam antibiotics in the studied community, indicates their important role in the development of complicated UTIs.

Synthesis and in vitro cholinesterase inhibitory potential of dihydropyridine derivatives.

Twelve derivatives of dihydropyridine derivatives (6-17) were synthesized and evaluated for in-vitro cholinesterases (AChE, BChE) inhibitory activity. All compounds showed potent activity with IC50 values between 0.21±0.003 to 147.14±0.12µM for AChE and among them five compounds showed potent activity with IC50 values 17.16±0.02 to 231.6±0.12µM for BChE when compared with standard Eserine (IC50 = 0.85±0.0001 µM (AChE) & 0.04±0.0001µM (BChE). The most potent compound 11 can be considered as potential lead compound showed an inhibition of 95.35±0.11 and IC50= 0.21±0.003 while compound 7 showed an inhibition of 83.45±0.13 and IC50= 17.16±0.02. It is concluded from structural activity relationship that the presence of nitro group at C-2 and C-4 position of dihydropyridine ring increase the acetyl cholinesterase and butyrylcholinesterase activities of these compounds while presence of -Br and -Cl also enhances the activities.

Biologically active scaffolds: Synthesis, characterization and studies of oxino bis-pyrazoles by environmental friendly method.

In the present communication, synthesis of bis-pyrazolones containing aryl motifs (4-14) and their α-glucosidase inhibitory activity, hemolytic and antihemolytic activities were reported. The newly synthesized compounds were characterized by analytical techniques such 1H-NMR, 13C-NMR, IR, mass spectrometry and compound No 4 additionally by X-ray crystallography. Compounds 4, 12, 14 were obtained in more than 85% yield. In comparison to typical acarbose (IC50 = 37.38±0.12µM), all synthesized compounds showed potent activity with IC50 values between 31.26±0.11 to 396.25±0.18µM. The most potent compounds 6, 8 and 11 showed IC50 values within the range of 31.26±0.11 to 37.48±0.12µM. Compounds 7, 10, 12 and 13 showed IC50 values within the range of 65.23±0.12 to 154.87±0.16µM, while compounds 4, 5 and 9 showed moderate inhibition with IC50 values 286.56±0.16 to 396.25±0.18µM. Structure-activity relationship (SAR) studies, suggests that electron withdrawing groups played a crucial role in enhancing α-glucosidase inhibitory effects of title compounds. In addition, results of the hemolytic and antihemolytic activity studies indicated that compound 13 possessed moderate levels of hemolytic and highest anti- hemolytic activity while 8 showed low anti- hemolytic and high hemolytic activity.

Microwave and conventional synthesis of Co (II), Cu (II) and Ni (II) metal complexes of some acid hydrazones with their spectral characterization and biological evaluation.

The transition metal complexes of Co(II), Ni(II), and Cu(II) derived from N'-((5-(2,5-dichlorophenyl)furan-2-yl)methylene)-2-hydroxybenzohydrazide (L24) and N'-((5-(2, 5-dichlorophenyl)furan-2-yl)methylene)benzohydrazide (L21) have been synthesized by conventional as well as microwave method being shorter time consuming, solvent less and gives improved yields as compared to the traditional conventional technique. These compounds were characterized by melting point, TLC, FTIR, 1H-NMR, elemental analysis, potentiometric titration, ICP-OES and EIMS. From this analytical data it is confirmed that complexes are in octahedral structure with coordination number 6 which revealed 1:2 (metal:ligand). FTIR data shows that these synthesized hydrazone ligands have ONO donor sites and coordinate with transition metal ions in a tridentate monobasic manner. All these synthesized compounds were tested for evaluation of antibacterial activity by agar disc diffusion assay and total antioxidant activity by Phosphomolybdenum method.

Gallstone Ileus With Cholecysto-Duodenal Fistula In An Elderly Male.

Gall stone ileus associated with cholecysto-duodenal fistula is a rare pathology. It most commonly presents in elderly females in 72-90% of cases. In such a case, a patient typically presents with recurrent attacks of sub-acute intestinal obstruction which usually resolves completely with conservative management only to recur again after some time. We are reporting a case of an 85-yearold gentleman who presented to us with gallstone ileus associated with cholecysto-duodenal fistula and his subsequent management. He underwent Laparotomy with enterotomy, stone extraction, Cholecystectomy and Graham's patch repair of the fistula. The purpose of this case report is to discuss a rare case of gall stone ileus associated with cholecysto-duodenal fistula. The diagnosis was confirmed using imaging and appropriate and timely surgical intervention for both mechanical intestinal obstruction and the fistula was undertaken.