Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

Objective

Aortic surgeries requiring hypothermic circulatory arrest evoke systemic inflammatory responses that often manifest as vasoplegia and hypotension. Because mast cells can rapidly release vasoactive and proinflammatory effectors, we investigated their role in intraoperative hypotension.

Curcumin encapsulated dual cross linked sodium alginate/montmorillonite polymeric composite beads for controlled drug delivery

The aim of the present work is fabrication of dual cross linked sodium alginate (SA)/montmorillonite (MMT) microbeads as a potential drug vehicle for extended release of curcumin (CUR). The microbeads were prepared using in situ ion-exchange followed by simple ionotropic gelation technique. The developed beads were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (X-RD) and scanning electron microscopy (SEM). The effect of MMT on encapsulation efficiency of CUR and intercalation kinetics was investigated. Dynamic swelling study and in vitro release study were investigated in simulated intestinal fluid (pH 7.4) and simulated gastric fluid (pH 1.2) at 37 °C. Results suggested that both the swelling and in vitro release studies were influenced by the pH of test media, which might be suitable for intestinal drug delivery. The release mechanism was analyzed by fitting the release data into Korsmeyer-Peppas equation.     

Association of − 757T > C polymorphism of C-reactive protein gene with chronic periodontitis of South Indian population

Inflammation Research - CRP gene polymorphism is common in inflammatory diseases, but such association has not been reported in periodontitis. Our objective was to interrogate SNPs of crp in...     

Structure-guided lead optimization of triazolopyrimidine-ring substituents identifies potent Plasmodium falciparum dihydroorotate dehydrogenase inhibitors with clinical candidate potential

Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmacokinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.