Methicillin resistant Staphylococcus aureus-importance of appropriate empirical therapy in serious infections

India has been titled the capital of antimicrobial resistance in the world with the centre for disease dynamics, economics andpolicy (CDDEP) predicting two million deaths in India by 2050. As per the World Health Organisation抯 global priority pathogen list of 2017, methicillin resistant Staphylococcus aureus(MRSA)has been classified as a 慼igh priority� pathogen due to its association with increased mortality rate, rising prevalence of resistance and increased burden on healthcare settings. A recent report by Indian Council of Medical Research signifies the exponential rise in the prevalence of MRSA in India, from 29% in 2009 to 39% in 2018. Serious MRSA infections are commonly associated with poor clinical outcomes coupled with increased hospitalisation stay and cost. Therefore, early identification and appropriate empiric treatment of MRSA plays a crucial role in healthcare settings. However, the constant rise in multi-drug resistance to the currently available anti-MRSA agents as well as their compromised safety profile limits its clinical use to manage severe MRSA infections. This review article explores the implications of severe MRSA infections and inappropriate empirical therapy on the clinical as well as economic outcomes. In addition, it also highlights limitations of the currently available anti-MRSA agentsand the need for newer agents to manage multi drug resistant (MDR)gram positive infections.

Modulation of Oxidative Stress, Serum Lipids and Renal Dysfunction by Benazepril in Diabetes Mellitus.

Present study assessed the effect of benazepril on oxidative stress, serum lipids and renal dysfunction in alloxan induced diabetic rabbits. Benazepril reversed the increase in level of malondialdehyde and decrease in level of glutathione and superoxide dismutase activity caused by induction of diabetes. It also had a beneficial effect on diabetic dyslipidemia as manifested by elevation in serum HDL cholesterol. However, it had no effect on serum LDL, total cholesterol or triglycerides. Benazepril also attenuated the renal dysfunction induced by diabetes. It resulted in significant reduction in blood urea, serum creatinine and urine albumin excretion as compared to diabetic control rabbits. Further, kidney weight was significantly less in benazepril treated rabbits as compared to diabetic rabbits. To conclude, benazepril was found to be effective in preventing the oxidative stress and renal dysfunction as well as beneficial on serum lipids in experimentally-induced diabetes mellitus.

Transglutaminases, thioredoxins and protein disulphide isomerase: diverse enzymes with a common goal of cross-linking proteins in lower organisms.

Prokaryotes and various eukaryotes have remarkable ability to survive under adverse physiologic conditions and protect themselves from environmental stresses. An important mechanism by which they accomplish this is by synthesizing rigid and biochemically inert structures around them. In general, these structures are highly stable and resistant to mechanical and chemical insults. Biochemically, they are composed of complex carbohydrates, such as chitin and heavily crosslinked scaffold of proteins to form complex structures, such as sheath, cuticle, and epicuticle. Transglutaminases (TGases) are a family of enzymes that share catalytic function with thioredoxin and protein disulphide isomerases (PDI) and catalyze protein crosslink reaction by establishing epsilon-(gamma-glutamyl)lysine isopeptide bonds. The isopeptide bonds thus formed are of great physiologic significance because once formed, they cannot be hydorlysed by any known enzymes of the eukaryote system and exhibit high resistance to reducing agents, detergents, and chaotropic agents. Therefore, it is likely that protective structures viz., sheath, cuticle, epicuticle, and viral core proteins synthesized by microorganisms involve active participation of TGases. In this review, we briefly describe the current knowledge of non-mammalian TGases and their possible role in growth, development, and survival of small organisms. Special reference is made to filarial nematode and bacterial TGases since they are the most well-characterized and studied enzymes among non-mammalian TGases.

Retinoic acid--a player that rules the game of life and death in neutrophils.

Neutrophils are the most prevalent white blood cells in the circulation. They represent the first line of defense against invading microorganisms and have been implicated in the pathogenesis of a number of human diseases. In response to various factors, the pluripotent stem cells in bone marrow differentiate into mature neutrophils, enter the blood stream, and die within 24 hr via apoptosis. Numerous defects can occur during the process of neutrophils' differentiation that can manifest in the form of a variety of clinical disorders. Retinoids (Vitamin A and analogues), in general, and all-trans retinoic acid (tRA), in particular, play a critical role during differentiation of neutrophils. tRA can directly modulate gene expression via binding to its nuclear receptors, which in turn, can activate transcription of genes that are essential for differentiation of immature cells to neutrophils. Involvement of retinoic acid receptor in pathogenesis of acute promyelocytic leukemia (APL), reflects an important role played by this receptor in differentiation of immature myeloid cells to neutrophils. This review summarizes evidence on involvement of retinoic acid-mediated events in differentiation process of neutrophils and their subsequent apoptosis.