Consensus recommendations for the management of hyperglycaemia in critically ill patients in the Indian setting.

Hyperglycaemia occurs frequently in critically-ill patients. Not only does it occur among patients with pre-existing diabetes mellitus but elevated blood glucose values during an acute illness can also be seen in previously glucose-tolerant individuals (stress hyperglycaemia). Numerous observational studies have shown an increase in morbidity and mortality in critically ill patients with hyperglycaemia. Interestingly, outcomes in individuals with stress hyperglycaemia are worse than that in critically ill hyperglycaemic patients with pre-existing diabetes. Proper management of hyperglycaemia has been shown to result in improved clinical outcomes. Critically ill patients with hyperglycaemia should primarily be managed with intravenous insulin infusion to allow dynamic adjustment of treatment to suit the rapid changes in blood glucose values in these patients. Currently, there are in existence a fair number of published protocols to administer intensive intravenous insulin therapy that range from the relatively simple to the fairly complex. Different management strategies have been proposed depending upon whether the critically ill hyperglycaemic patient is stationed in the emergency department, the medical intensive care unit (ICU), the surgical ICU or the coronary care unit. Moreover, the ideal target blood glucose value to maintain in this group of patients remains controversial. Keeping these issues in mind, a group of leading experts in the fields of diabetes and critical care extensively reviewed the literature and framed recommendations with special attention to clinical practice in India. The aim was to formulate recommendations which are based on sound evidence and yet are simple and easy to understand and implement across the ICU throughout the country. In the current recommendations, intensive intravenous insulin therapy has been suggested as the preferred mode of managing hyperglycaemia in patients admitted to critical care settings. The current recommendations suggest using a simple and similar protocol for managing hyperglycaemia in critically-ill patients irrespective of their location among the various critical care units in a hospital. Recommendations have also been made for transition from intravenous to subcutaneous administration of insulin when the patient is transferred out of the critical care setting. It is hoped that the current recommendations shall form the basis for the management of hyperglycaemia in critically ill patients across the country.

Mechanistic evaluation of the signaling events regulating curcumin-mediated chemosensitization of breast cancer cells to 5-fluorouracil.

5-Fluorouracil (5-FU) is the first rationally designed antimetabolite, which achieves its therapeutic efficacy through inhibition of the enzyme thymidylate synthase (TS), which is essential for the synthesis and repair of DNA. However, prolonged exposure to 5-FU induces TS overexpression, which leads to 5-FU resistance in cancer cells. Several studies have identified curcumin as a potent chemosensitizer against chemoresistance induced by various chemotherapeutic drugs. In this study, we report for the first time, with mechanism-based evidences, that curcumin can effectively chemosensitize breast cancer cells to 5-FU, thereby reducing the toxicity and drug resistance. We found that 10 µM 5-FU and 10 µM curcumin induces a synergistic cytotoxic effect in different breast cancer cells, independent of their receptor status, through the enhancement of apoptosis. Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-κB (NF-κB), and this observation was confirmed by silencing TS and inactivating NF-κB, both of which reduced the chemosensitizing efficacy of curcumin. Silencing of TS suppressed 5-FU-induced NF-κB activation, whereas inactivation of NF-κB did not affect 5-FU-induced TS upregulation, confirming that TS is upstream of NF-κB and regulates the activation of NF-κB in 5-FU-induced signaling pathway. Although Akt/PI3kinase and mitogen-activated protein kinase pathways are activated by 5-FU and downregulated by curcumin, they do not have any role in regulating the synergism. As curcumin is a pharmacologically safe and cost-effective compound, its use in combination with 5-FU may improve the therapeutic index of 5-FU, if corroborated by in vivo studies and clinical trials.

Expression of diverse midgut serine proteinases in the sericigenous Lepidoptera Antheraea assamensis (Helfer) is influenced by choice of host plant species.

Antheraea assamensis is reared on various species of the Lauraceae family from north-east India for its distinctive cocoon silk. We demonstrate differential expression of digestive trypsin and chymotrypsins in larvae feeding on a primary host, Persea bombycina Kosterm., in comparison to larvae feeding on Litsea monopetala Roxb. using in vitro proteolytic assays, zymogram analyses with proteinase inhibitors, restriction digestion of RNA-PCR amplicons and quantitative real-time PCR (RT-PCR). Eight novel members of the serine proteinase gene family were identified, including an intron-spliced trypsin (AaPb4) and seven putative chymotrypsins (AaPb2, AaPb4, AaPb12, AaLm4, AaLm6, AaLm19 and AaLm29). Midgut transcript levels of the putative trypsin were higher in larvae fed P. bombycina whereas levels of transcripts encoding putative chymotrypsins were higher in larvae reared on L. monopetala. Complex, differential expression of sequence divergent midgut serine proteinases may reflect the ability of lepidopteran larvae to feed on different species of host plants. Possible implications of host plant choice on the digestive physiology of A. assamensis are discussed.

Surgical experience with dissecting and nondissecting aneurysms of the ascending aorta.

BACKGROUND: Patients who underwent replacement of the ascending aorta with a prosthetic graft for treatment of ascending aortic aneurysm and dissection between January 1992 and December 2000 were studied. METHODS AND RESULTS: Bentall's operation, using a composite aortic valve and prosthetic graft. was performed in 82 patients (70 males). Indications for the procedure included ascending aortic aneurysm (n=54 including 16 patients with Marfan's syndrome): DeBakey Type I or II aortic dissection (n=26 including 10 patients with Marfan's syndrome) and ascending aortic aneurysm with severe aortic stenosis (bicuspid aortic valve disease) (n=2). Bentall's procedure with the inclusion technique was performed in 72 patients and a Cabrol fistula created in 63 patients. In 10 other patients, coronary button transfer was done without a Cabrol fistula. There were 6 early deaths (7.3%) and 8 patients required re-exploration for excessive bleeding. Eighteen patients showed low cardiac output while the wound of 8 became infected. Postoperative arrhythmia and renal failure was seen in 26 and 6 patients, respectively. Four patients had pericardial effusion. Follow-up ranged from 1 month to 8 years. There were 8 late deaths, the causes of which include congestive heart failure (n=3). cerebral hemorrhage (n=3) and sudden cardiac death (n=2). Two patients reported back with dissection of the descending thoracic aorta and await surgery. CONCLUSIONS: Bentall's operation is a safe procedure with an acceptable mortality and morbidity.

Biochemical Markers of Myocardial Injury during Coronary Artery Bypass Grafting with and without Cardiopulmonary Bypass.

Minimally invasive cardiac surgical techniques have been applied recently in the management of variety of cardiac lesions. Between December 1998 and February 1999, fifty patients underwent coronary artery bypass grafting (CABG) under two different techniques. In group A (twenty five patients), CABG was done under cardiopulmonary bypass (CPB) and in group B (twenty three patients), CABG was performed on a 'beating heart' without CPB. Serum concentration of cardiac specific enzymes CPZ-MB and Troponin-T were estimated in all the patients from pre-induction period to 72 hours after the bypass graft. Group A patients exhibited a significant (P<0.05) elevation in the CPK-MB and Troponin-T level as compared to group B. Our results show that the extent of myocardial damage following CABG is significantly less when the procedure is done on a 'beating heart'.

Studies on the pathological effects of feeding betel-nut meal in albino rats.

The pathological effects of betel-nut meal consumption in weaned albino rats were studied for a period of 4 weeks. In higher concentrations (60-100%), toxic effects were observed. The rats showed severe diarrhoea and died within 1-3 weeks depending upon the amount of betel-nut meal consumed. In lower concentrations (5-10%), no grossly detectable pathological changes were observed in any one of the experimental rats. With the increase in the concentration of betel-nut meal in the experimental diets, the pathological changes were intensified gradually. The pathological changes observed in the rats fed with experimental diets containing more than 15% betel-nut meal were necrosis of the buccal and intestinal mucosa, splenomegaly, fatty changes in the liver and stunted skeletal growth. Catarrhal enteritis was observed in the rats fed with 15% betel-nut meal and haemorrhagic gastroenteritis was observed when the concentration of the betel-nut meal was raised above 15%.