Use of Pavo cristatus feather extract for the better management of snakebites: neutralization of inflammatory reactions

In Indian traditional medicine, peacock feather in the form of ash (Bhasma) or water extract are used against snakebite and to treat various problems associated with lungs. This study was aimed to evaluate the water extract of peacock feather (PCF) against the local tissue damage caused due to snakebite. PCF water extract showed inhibition towards phospholipase A2 enzyme activity from snake venom (Naja naja and Vipera russelii), inflammatory fluids (synovial, pleural, ascites) and normal serum in a dose-dependent manner. Hyaluronidase and proteases are other major enzymes in snake venoms responsible for local tissue damage. PCF water extract inhibited hyaluronidase and proteolytic enzyme activities from Vipera russelii, Naja naja and Trimeresurus malabaricus venom. The active principle is a hydrophilic molecule easily extractable in water or polar solvents. PCF water extract gave positive results for the presence of protein and secondary metabolites like carotenoids and steroids. Analysis of metal ions revealed that iron is the major ion (> 20-fold). Other metal ions detected in smaller amount are copper, chromium, zinc and nickel. The least amount of ion detected is gold. Co-injection of PCF water extract with snake venom and inflammatory PLA2 enzymes neutralize the edema inducing activity of all the PLA2 enzymes studied. Since it inhibits hyaluronidase and proteases enzyme activity from snake venom PCF water extract is a powerful neutralizing agent, which has therapeutic application against venom toxicity.     

Acquired bone marrow failure after diphtheria

Acquired bone marrow failure can result after infections caused by viruses, exposure to toxins, or chemicals. Majority of acquired cases of marrow failure labeled as "idiopathic" are probably immune mediated through activated T-cells and cytokines. We observed pancytopenia in the second week, after pharyngeal diphtheria in a 14-year-old child. Bone marrow examination showed reduced marrow precursors affecting all 3 cell lines. There are no clinical cases of myelosuppression reported in diphtheria infection and this is probably the first reported case of bone marrow failure after diphtheria infection. However, such observations merit further evaluation and confirmation by experimental studies.     

Gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population

Genetic association studies have implicated the TSNAX/DISC1 (disrupted in schizophrenia 1) in schizophrenia (SCZ), bipolar affective disorder (BPAD) and major depression. This study was performed to assess the possible involvement of TSNAX/DISC1 locus in the aetiology of BPAD and SCZ in the Southern Indian population. We genotyped seven single nucleotide polymorphism (SNPs) from TSNAX/DISC1 region in 1252 individuals (419 BPAD patients, 408 SCZ patients and 425 controls). Binary logistic regression revealed a nominal association for rs821616 in DISC1 for BPAD and also combined cases of BPAD or SCZ, but after correcting for multiple testing, these results were non-significant. However, significant association was observed with BPAD, as well as combined cases of BPAD or SCZ, within the female subjects for the rs766288 after applying false discovery rate corrections at the 0.05 level. Two-locus analysis showed C-C (rs766288-rs2812393) as a risk combination in BPAD, and G-T (rs2812393-rs821616) as a protective combination in SCZ and combined cases of BPAD or SCZ. Female-specific associations were observed for rs766288-rs2812393, rs766288-rs821616 and rs8212393-rs821616 in two-locus analysis. Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD.     

Plasmodium falciparum histones induce endothelial proinflammatory response and barrier dysfunction

Plasmodium falciparum is a protozoan parasite of human erythrocytes that causes the most severe form of malaria. Severe P. falciparum infection is associated with endothelial activation and permeability, which are important determinants of the outcome of the infection. How endothelial cells become activated is not fully understood, particularly with regard to the effects of parasite subcomponents. We demonstrated that P. falciparum histones extracted from merozoites (HeH) directly stimulated the production of IL-8 and other inflammatory mediators by primary human dermal microvascular endothelial cells through a signaling pathway that involves Src family kinases and p38 MAPK. The stimulatory effect of HeH and recombinant P. falciparum H3 (PfH3) was abrogated by histone-specific antibodies. The release of nuclear contents on rupture of infected erythrocytes was captured by live cell imaging and confirmed by detecting nucleosomes in the supernatants of parasite cultures. HeH and recombinant parasite histones also induced endothelial permeability through a charge-dependent mechanism that resulted in disruption of junctional protein expression and cell death. Recombinant human activated protein C cleaved HeH and PfH3 and abrogated their proinflammatory effects. Circulating nucleosomes of both human and parasite origin were detected in the plasma of patients with falciparum malaria and correlated positively with disease severity. These results support a pathogenic role for both host- and pathogen-derived histones in P. falciparum-caused malaria.     

Intermediate to long-term outcome following congenital coronary artery fistulae closure with focus on thrombus formation

We sought to evaluate intermediate to long-term follow-up after coronary artery fistula (CAF) closure with emphasis on thrombotic complications. Transcatheter closure (TCC) or surgical closure (SC) is the current standard of treatment for significant CAF. Incidence and risk factors of coronary thrombosis after CAF closure have not been well described. Patients with CAF were identified from a departmental database and their medical records were retrospectively reviewed. CAFs were classified as proximal or distal based on origin and size as small, medium, or large. Of 16 patients, 12 underwent TCC and 4 SC. Median follow-up was 2.3 years (0.1 to 41.6). Myocardial infarction (MI) related to coronary thrombosis occurred in 3 patients; immediately, 0.9 year, and 42 years after closure. Ages at MI were 9.2, 57, and 49 years. All 3 had distal, large CAFs and underwent SC. Anticoagulation was used in 2 of 3 patients. In the remaining 13 patients, TCC was performed in 12 and SC in 1; mean age was 13.8 years (0.1 to 38.9). CAFs were proximal in 10 and distal in 3 and large in 10 and medium in 3. On follow-up, these patients were asymptomatic without MI. Anticoagulation was used in 9 of 13 after closure. In conclusion, patients with CAF are at risk for coronary artery thrombosis and MI after closure. Patients with distal type, large CAF, and older age at presentation may be at higher risk for coronary thrombosis. Close follow-up with anatomic and functional coronary evaluation is warranted in all patients after CAF closure.