Genetic diversity of Indian Plasmodium vivax isolates based on the analysis of PvMSP3ß polymorphic marker.

BACKGROUND: Malaria is one of the major communicable diseases in India and worldwide. PvMSP3ß is a highly polymorphic gene due to its large insertions and deletions in the central alanine-rich region, which, in turn, makes it a valuable marker for population genetic analysis. Very few studies are available from India about the genetic diversity of Plasmodium vivax based on PvMSP3ß gene, and hence, this study was designed to understand the molecular diversity of the P. vivax malaria parasite. The accumulating epidemiological data provide insights into the circulating genetic variants of P. vivax in India, and ultimately benefits the vaccine development. MATERIALS AND METHODS: A total of 268 samples confirmed to be positive by microscopy, rapid diagnostic test, and quantitative buffy coat test were collected from four different regions of India (Puducherry, Mangaluru, Jodhpur, and Cuttack) in the present study. Polymerase chain reaction (PCR)-based diagnosis was carried out to confirm the P. vivax monoinfection, and only the mono-infected samples were subjected to PvMSP3ß gene amplification and further restriction fragment length polymorphism (RFLP) to determine suballeles. RESULTS: Based on the size of the amplified fragment, the PvMSP3ß gene was apportioned into two major types, namely Type A genotype (1.6-2 Kb) was predominantly present in 148 isolates and Type B (1-1.5 Kb) was observed in 110 isolates. The percentage of mixed infections by PCR was 3.73%. All the PCR products were subjected to RFLP to categorize into suballeles and we detected 39 suballeles (A1-A39) in Type A, and 23 suballeles (B1-B23) in Type B genotype. A high degree of diversity was observed among the isolates collected from Mangaluru region when compared to isolates collected from other regions. CONCLUSION: The present study showed a high degree of genetic diversity of PvMSP3ß gene among the isolates collected from various parts of India. High polymorphism in PvMSP3ß gene makes it a promising marker for epidemiological and vaccine development studies.

Application of nitric oxide and carbon monoxide in a model of renal preservation.

BACKGROUND: Nitric oxide and carbon monoxide exert vasodilatory effects that minimize ischaemia-reperfusion injury. An isolated porcine kidney model was used to assess the effects of administering the nitric oxide donor sodium nitroprusside (SNP) and carbon monoxide-releasing molecule (CORM) 3 during a period of warm preservation followed by reperfusion. METHODS: Kidneys were perfused under warm preservation conditions after 10 min of warm ischaemia and 16 h of cold storage in four groups: SNP, control, CORM-3 and inactive CORM-3 (inactive control). Renal function and viability were assessed. RESULTS: SNP and CORM-3 increased renal blood flow (RBF) during warm preservation (P = 0.014). After reperfusion, RBF was significantly improved in the CORM-3 group compared with the control group (P = 0.019). The reduction in creatinine clearance was significantly less in the CORM-3 group than in the inactive CORM-3 group (P = 0.021), and serum creatinine levels were significantly lower (P = 0.029). There was a negative correlation between RBF during warm preservation and functional parameters during reperfusion (creatinine concentration: r(s) = - 0.722, P < 0.001; sodium excretion: r(s) = - 0.912, P < 0.001). CONCLUSION: The beneficial vasodilatory effects of CORM-3 during warm preservation improved renal function during reperfusion; SNP exerted similar, although less pronounced, effects.

Case report vancomycin -resistant Enterococcus faecium VanA phenotype: first documented isolation in India.

In recent years, vancomycin-resistant enterococci, especially Enterococcus faecium has emerged as an important nososcomial pathogen and represents a serious threat to patients with impaired host defences. We report infection with vancomycin-resistant Enterococcus faecium in a 3-year-old child with patent ductus arteriosus. The organism, isolated from a central venous catheter tip, exhibited a high-level resistance to vancomycin (minimum inhibitory concentration > or = 256 microg/ ml) and was also resistant to teicoplanin. The child probably died due to sepsis from this highly resistant organism. To the best of our knowledge, this is the first reported isolation of VanA phenotype Enterococcus faecium in India.

Influence of a novel inhibitor (UM8190) of prolylcarboxypeptidase (PRCP) on appetite and thrombosis.

Preclinical pharmacological characterization of a novel inhibitor (UM8190) of prolylcarboxypeptidase (PRCP) was investigated. We synthesized and evaluated a library of proline-based analogs as prospective recombinant PRCP (rPRCP) inhibitors and inhibitors of PRCP-dependent prekallikrein (PK) activation on human pulmonary artery endothelial cells (HPAEC). Among the newly synthesized compounds, UM8190 was further characterized in vivo using methods that encompassed a mouse carotid artery thrombosis model and animal model of food consumption. (S)-N-dodecyl-1-((S)-pyrrolidine-2-carbonyl) pyrrolidine-2-carboxamide [Compound 3 (UM8190)] was selected for further evaluation from the initial assessment of its PRCP inhibitory action (K(i)= 43 µM) coupled with its ability to block PRCP-dependent PK activation on HPAEC (K(i)= 34 µM). UM8190 demonstrated excellent selectivity against a panel of carboxypeptidases and serine proteases and blocked bradykinin (BK) generation and BK-induced permeability by 100%, suggesting that it may be useful in preventing the local production of large amounts of BK. Furthermore, UM8190 showed an anorexigenic effect when systemically administered to fasted mice, reducing food intake in a dose- and time-dependent manner. In a mouse carotid artery thrombosis model, it also demonstrated an antithrombotic effect. UM8190 is a selective PRCP inhibitor and it may represent a new anorexigenic, and antithrombotic drug, that works by inhibiting PRCP-mediated mechanisms.