Genetic & epigenetic approach to human obesity.

Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

Differential effects of non-steroidal anti-inflammatory drugs on mitochondrial dysfunction during oxidative stress.

We investigated the effects of several non-steroidal anti-inflammatory drugs on swelling related properties of mitochondria, with an emphasis on compounds that are marketed and utilized topically in the eye (nepafenac, ketorolac, diclofenac, bromfenac), and compared these to the effects of amfenac (a metabolite of nepafenac) and to celecoxib (active principle of Celebrex). With the exception of the last compound, none of the drugs promote swelling of normal mitochondria that are well energized by succinate oxidation. However, swelling is seen when the mitochondria are under an oxidative stress due to the presence of t-butylhydroperoxide. When used at 200 microM the order of potency is celecoxib > bromfenac > diclofenac > ketorolac > amfenac > nepafenac approximately equal to 0. Again with the exception of celecoxib, this swelling is not seen when mitochondria are depleted of endogenous Ca(2+) and is accelerated when exogenous Ca(2+) is provided. Sr(2+) does not substitute for exogenous Ca(2+) and prevents swelling in the presence of endogenous Ca(2+) only. The same is true for ruthenium red (inhibitor of the Ca(2+) uniporter), for cyclosporin A (inhibitor of the mitochondrial permeability transition), and for a 3.4 kDa polyethylene glycol (polymer that cancels the force which drives swelling following the permeability transition). It is concluded that several non-steroidal anti-inflammatory drugs promote the mitochondrial permeability transition under conditions of oxidative stress and in a Ca(2+) dependent fashion, whereas celecoxib functions by another mechanism. Potency of those compounds that promote the transition varies widely with bromfenac being the most potent and nepafenac having almost no effect. The mitochondrial dysfunction which is caused by the transition may underlie side effects that are produced by some of these compounds.

Changing pattern of oral cavity lesions and personal habits over a decade: hospital based record analysis from allahabad.

AIM: To do a prospective clinicohistological study of premalignant and malignant lesions of the oral cavity, and compare it with a 10-year retrospective data, especially in terms of incidence, age distribution, personal habits, and site and type of lesion. MATERIAL AND METHODS: Sections from 776 lesions of the oral cavity, which included 647 lesions of a 10-year (1993 - 2003) retrospective study and 129 lesions of a one-year (2003 - 2004) prospective study, were observed clinically, and a histological correlation was carried out. RESULTS: Premalignant lesions included 78 cases of leukoplakia, 68 cases of oral submucous fibrosis, and 76 cases of squamous papilloma. Their incidence has increased in the last decade from 0.15 to 0.53. These lesions commonly presented in the fourth decade of life, as white patches in leukoplakia and oral submucous fibrosis, and as a growth in squamous cell papilloma. Squamous cell carcinoma was the commonest lesion (57%). Its incidence has increased significantly in the last decade. The mean age of presentation was the sixth decade. A personal history of tobacco chewing was given by most of the patients in the retrospective group, while the use of pan masala was found to be maximum in the prospective group. The overall agreement between the clinical and histological diagnosis was 95.36% (740 / 776) and the kappa coefficient of agreement was 0.9256. CONCLUSION: Histology along with a detailed clinical workup was found to be a useful, reliable, and accurate diagnostic technique for lesions of the oral cavity. An increase in premalignant lesions in the prospective study, associated with increased pan masala intake is alarming and needs to be taken care of.