Kashi Nath Prasad

New Delhi metallo-beta-lactamase (NDM)-mediated carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii is a major concern. We investigated the presence of NDM and its variants in P. aeruginosa and A. baumannii at a tertiary hospital in North India. A total of 236 isolates (130 P. aeruginosa and 106 A. baumannii ) were included; 38 (29.23%) P. aeruginosa and 20 A. baumannii isolates (18.8%) were resistant to carbapenems and all of them were bla _NDM positive. All 38 carbapenem-resistant P. aeruginosa harbored bla _NDM-1, while 12 (60%) of 20 A. baumannii harbored bla _NDM-2 . Pulsed-field gel electrophoresis showed that all 58 isolates were clonally unrelated. By Southern blot analysis, bla _NDM-2 was located on chromosome. The bla _NDM-2 -positive isolates were more frequently recovered from tracheal aspirate (67% vs.16%; p = 0.02) and intensive care unit (67% vs. 20%; p = 0.001) than bla _NDM-1 . Among other carbapenemases, VIM was significantly associated with bla _NDM-1 than bla _NDM-2 (61% vs. 17%; p = 0.006). Mortality between bla _NDM-1 - and bla _NDM-2 -infected patients was comparable. When expressed in Escherichia coli , bla _NDM-2 transformant conferred one doubling dilution higher MIC value for cefotaxime, piperacillin/tazobactam than bla _NDM-1 . The study shows the emergence of bla _NDM- mediated resistance among P. aeruginosa and A. baumannii and rapid evolution of bla _NDM-2 in A. baumannii with its chromosomal localization.

Objective: To investigate the frequency and integrity of certain cag pathogenicity island genes (cagPAI) in Helicobacter pylori strains and their association with peptic ulcer disease (PUD) and gastric cancer. Material and Methods: We enrolled 240 adult patients [120 with functional dyspepsia (FD), 50 with PUD and 70 with gastric cancer] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed when either culture or any two of the three tests (rapid urease test, histopathology and specific ureA PCR) were positive. DNA extracted from H. pylori isolates and positive gastric tissues were tested by PCR for the presence of different genes of cagPAI using specific primers. Results: A total of 122 (51%) patients were H. pylori positive. Frequencies of cagPAI genes cagA, cagE, cagT and cagM in H. pylori strains from different groups of patients were as follows: functional dyspepsia 73, 83, 76 and 60%, PUD 70, 94, 91, 70% and gastric cancer 75, 95, 90 and 70%, respectively. Risk associated for the presence of PUD and gastric cancer with cagPAI genes cagE, cagT and cagM was 5.0-, 4.6- and 4.1- and 3.0-, 2.8- and 2.5-folds, respectively. Prevalence of intact cagPAI was significantly higher in PUD and gastric cancer compared to functional dyspepsia (PUD vs. functional dyspepsia, 71% vs. 38%, P = 0.01; gastric cancer vs. functional dyspepsia, 75% vs. 38%, P < 0.01). Intact cagPAI was associated with increased risk for the presence of PUD (odds ratio 5.2, 95% CI 2.4–11.3) and for the presence of gastric cancer (odds ratio 4.5, 95% CI 2.3–7.1). Conclusions: cagPAI integrity and its different genes are linked to different forms of gastric disease and so may have a role in pathogenesis, diagnosis and management.

Purpose: Guillain–Barré syndrome (GBS) is an acute inflammatory, autoimmune disorder of peripheral nervous system. Interleukin-17 (IL-17) and intercellular adhesion molecule-1 (ICAM-1) polymorphisms with higher expression levels have already been studied in many inflammatory and autoimmune diseases. However, the possible role of IL-17 and ICAM-1 polymorphisms in GBS remains unknown. Therefore, the current study investigated IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms. Materials and method: In this study, total 80 GBS patients and 75 normal healthy controls were included. IL-17 (His161Arg and Glu126Gly) and ICAM-1 (Gly241Arg) polymorphisms were performed using polymerase chain reaction –restriction fragment length polymorphism analysis. Further, the expression of ICAM-1 and IL-17 was determined by reverse-transcriptase PCR and enzyme-linked immunosorbent assay. Results: IL-17 (Glu126Gly) mutant and ICAM-1 (Gly241Arg) heterozygous genotypes were strongly associated with increased risk of GBS (p < 0.016; OR = 3.706, 95% CI = 1.28–10.67; p < 0.001; OR = 4.148, 95% CI = 2.119–8.119, respectively). IL-17 and ICAM-1 genes showed significantly higher expression in GBS when compared with healthy controls. Conclusion: IL-17 and ICAM-1 polymorphisms showed significant association with GBS and their enhanced expressions have possible role in GBS development. IL-17 and ICAM-1 polymorphisms could be genetic markers to GBS susceptibility.

Neurocysticercosis (NCC), caused by cysticerci of Taenia solium is the most common helminthic infection of the central nervous system. Some individuals harboring different stages of cysticerci in the brain remain asymptomatic, while others with similar cysticerci lesions develop symptoms and the reasons remain largely unknown. Inflammatory response to antigens of dying parasite is said to be responsible for symptomatic disease. Reactive oxygen species (ROS) that are generated in inflammatory conditions can damage cellular macromolecules such as lipids, DNA, and proteins. The glutathione S-transferases (GSTs) are critical for the protection of cells from ROS. A total of 250 individuals were included in the study: symptomatic NCC = 75, asymptomatic NCC = 75, and healthy controls = 100. The individuals carrying the deletions of GSTM1 and GSTT1 were at risk for NCC (OR = 2.99, 95 %CI = 1.31–6.82, p = 0.0073 and OR = 1.94, 95 %CI = 0.98–3.82, p = 0.0550 respectively). Further, the individuals with these deletions were more likely to develop symptomatic disease (OR = 5.08, 95 % CI = 2.12–12.18, p = 0.0001 for GSTM1 and OR = 3.25, 95 %CI = 1.55–6.82, p = 0.0018 for GSTT1). Genetic variants of GSTM3 and GSTP1 were not associated with NCC. The total GST activity and levels of GSTM1, GSTT1, and GSTM3 were significantly higher in asymptomatic subjects than in symptomatic and healthy controls. Lower GST activity was observed in individuals with GSTM1 and GSTT1 deletions. The present study suggests that the individuals with GSTM1 and GSTT1 deletions are at higher risk to develop symptomatic disease. The higher GST activity and levels of GSTM1, GSTT1, and GSTM3 are likely to play role in maintaining asymptomatic condition.

Mutations in the oncogene and tumour suppressor genes play an important role in carcinogenesis. We investigated the association of p53 and K-ras gene mutation and Helicobacter pylori infection in patients with gastric cancer (GC) and peptic ulcer disease (PUD) attending a tertiary care hospital in north India. In total, 348 adult patients [62 GC, 45 PUD and 241 non-ulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Mutation in the exon 5-8 of p53 gene was analyzed by PCR-single stranded conformational polymorphism (SSCP) and confirmed by sequence analysis. K-ras gene codon 12 mutation was analyzed by PCR-based restriction fragment length polymorphism. Overall p53 gene mutation was found in 4.6 per cent of the study population, and its distribution in GC, PUD and NUD was 21, 4.4 and 0.4 per cent, respectively. p53 gene mutation was significantly higher in patients with GC than PUD (P<0.05) and NUD (P<0.001). No difference in p53 gene mutation was observed between H. pylori infected and non-infected individuals. K-ras gene mutation was absent in all the patients. Our results show that p53 gene mutation may be associated with gastric carcinogenesis independent to H. pylori infection and absence of K-ras gene mutation questions its role in the pathogenesis of GC and PUD in Indian patients.