Occurrence of co-infection with dengue viruses during 2014 in New Delhi, India.

Dengue fever is an arthropod-borne viral infection that has become endemic in several parts of India including Delhi. We studied occurrence of co-infection with dengue viruses during an outbreak in New Delhi, India in 2014. For the present study, blood samples collected from symptomatic patients were analysed by RT-PCR. Eighty percent of the samples were positive for dengue virus. The result showed that DENV-1 (77%) was the predominant serotype followed by DENV-2 (60%). Concurrent infection with more than one serotype was identified in 43% of the positive samples. Phylogenetic analysis clustered DENV-1 strains with the American African and DENV-2 strains in Cosmopolitan genotypes. Four common amino-acid mutations were identified in the envelope gene of DENV-1 sequences (F337I, A369T, V380I and L402F) and one common mutation (N390S) in the DENV-2 sequences. Further analysis revealed purifying selection in both the serotypes. A significant number of patients were co-infected with DENV-1 and DENV-2 serotypes. Although we do not have direct evidence to demonstrate co-evolution of these two stereotypes, nonetheless their simultaneous occurrence does indicate that they are favoured by evolutionary forces. An ongoing surveillance and careful analysis of future outbreaks will strengthen the concept of co-evolution or otherwise. Whether the concurrent dengue viral infection is correlated with disease severity in a given population is another aspect to be pursued. This study is envisaged to be useful for future reference in the context of overall epidemiology.

Effects of thyroid hormone analogue and a leukotrienes pathway-blocker on reperfusion injury attenuation after heart transplantation.

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF- α , IL-1 ß , and ICAM-1 and plasma level of cTnI (P < 0.05). Morphologic analysis showed that both MK-886 and DITPA markedly improved (P < 0.05) the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

Hypoxia-induced caspase-3 activation and DNA fragmentation in cortical neurons of newborn piglets: role of nitric oxide.

Hypoxia results in generation of nitric oxide (NO) free radicals, activation of caspase-3, and genomic DNA fragmentation. The present study tests the hypothesis that hypoxia-induced caspase-3 activation and DNA fragmentation are nitric oxide mediated. Studies were conducted in newborn piglets, divided into normoxic (n = 5), hypoxic (n = 5), and hypoxic-7-NINA (n = 6). Hypoxic-7-NINA group received the neuronal nitric oxide synthase inhibitor, 7-Nitroindazole (7-NINA). Caspase-3 activity was determined spectrofluorometrically using enzyme-specific substrates. Sections from the neocortex were stained with an antiserum recognizing active caspase-3. Purified DNA was separated by gel electrophoresis. Administration of 7-NINA resulted in decreased immunoreactivity of caspase-3 (mean LI: 20.2%) as compared to the untreated hypoxia group (mean LI: 57.5%) (P < 0.05). 7-NINA attenuated caspase-3 enzymatic activity as well in comparison to the untreated hypoxia group (P < 0.05). Furthermore, multiple low molecular weight bands corresponding to DNA fragments were present in the hypoxic but not in the normoxic or hypoxic-7-NINA groups. Inhibition of nNOS abates the hypoxia-induced increase in active caspase-3 immunoreactivity, as well as enzymatic activity in cortical neurons, and DNA fragmentation in brain homogenates. We conclude that the coordinate increase of capase-3 activity and fragmentation of nuclear DNA in the hypoxic newborn piglet brain are NO mediated.