Proinflammatory cytokines and the oxidative stress response are reported to be involved in dengue viral disease. The present study investigated the correlation of proinflammatory cytokines and lipid peroxidation with dengue severity. Clinical samples from 27 dengue fever (DF) cases, 30 dengue haemorrhagic fever (DHF) cases, and 24 dengue shock syndrome (DSS) cases were studied around defervescence, along with samples from 30 healthy controls. Plasma samples were analysed for tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) by ELISA and for malondialdehyde (MDA) by thiobarbituric acid assay. Dengue-infected individuals had significantly higher levels of TNF-α, IFN-γ, and MDA in comparison to controls. The ratio of TNF-α to IFN-γ was significantly higher in DHF and DSS than in DF. A TNF-α/IFN-γ ratio value of 5.69 around defervescence predicted DHF and DSS with moderate accuracy and thus may serve as an indicator to study dengue severity. The study observed a significant positive correlation of lipid peroxides with TNF-α levels and the TNF-α/IFN-γ ratio in severe dengue cases. We propose that the oxidative stress response induced by the dengue virus may trigger the inflammatory cytokine responses in dengue severity and thereby contributes to the pathogenesis of the disease; however the interplay between the oxidative response and inflammatory activity in disease virulence needs further study.

A convenient catalyst-free, three-component procedure was developed for the synthesis of tetrasubstituted pyrroles under solvent-free conditions and in green solvents glycerol, PEG-200 and water. A sequential enamine-formation, Michael addition and intramolecular cyclization of primary amines, 1,3-dicarbonyl compounds and isatin-derived Michael acceptors afforded 3-(1H-pyrrol-3-yl)indolin-2-ones in excellent yields. In this simple one-pot transformation the requirement of column chromatography purification of the products was completely avoided. Besides, the method is highly environmentally benign and atom-economical, and the only side product of this reaction was two molecules of water. A comparative study for the four developed conditions showed that the solvent-free conditions were superior regardless of the nature of the starting materials, and the green solvents were effective for alkyl and benzylamines affording higher yields compared to arylamines. The preliminary in vitro cytotoxic studies of a representative compound against Ehrlich's ascites carcinoma (EAC) tumor cells showed significant activity with a CTC₅₀ value of 15.64 μM.