Antiepileptic drugs and bone metabolism

Anti-epileptic medications encompass a wide range of drugs including anticonvulsants, benzodiazepines, enzyme inducers or inhibitors, with a variety effects, including induction of cytochrome P450 and other enzyme, which may lead to catabolism of vitamin D and hypocalcemia and other effects that may significantly effect the risk for low bone mass and fractures. With the current estimates of 50 million people worldwide with epilepsy together with the rapid increase in utilization of these medications for other indications, bone disease associated with the use of anti-epileptic medications is emerging as a serious health threat for millions of people. Nevertheless, it usually goes unrecognized and untreated. In this review we discuss the pathophysiologic mechanisms of bone disease associated with anti-epileptic use, including effect of anti-epileptic agents on bone turnover and fracture risk, highlighting various strategies for prevention of bone loss and associated fractures a rapidly increasing vulnerable population

Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells

The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8–10 nm), and relatively high T2 relaxivity (R2 = 222L · mmol−1 · sec−l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer

Differential effect of obesity on bone mineral density in White, Hispanic and African American women: a cross sectional study

Osteoporosis is a major public health problem with low bone mass affecting nearly half the women aged 50 years or older. Evidence from various studies has shown that higher body mass index (BMI) is a protective factor for bone mineral density (BMD). Most of the evidence, however, is from studies with Caucasian women and it is unclear to what extent ethnicity plays a role in modifying the effect of BMI on BMD. A cross sectional study was performed in which records of postmenopausal women who presented for screening for osteoporosis at 2 urban medical centres were reviewed. Using logistic regression, we examined the interaction of race and BMI after adjusting for age, family history of osteoporosis, maternal fracture, smoking, and sedentary lifestyle on BMD. Low BMD was defined as T-score at the lumbar spine < -1. Among 3,206 patients identified, the mean age of the study population was 58.3 ± 0.24 (Years ± SEM) and the BMI was 30.6 kg/m(2). 2,417 (75.4%) were African Americans (AA), 441(13.6%) were Whites and 348 (10.9%) were Hispanics. The AA women had lower odds of having low BMD compared to Whites [Odds ratio (OR) = 0.079 (0.03–0.24) (95% CI), p < 0.01]. The odds ratio of low BMD was not statistically significant between White and Hispanic women. We examined the interaction between race and BMD. For White women; as the BMI increases by unity, the odds of low BMD decreases [OR = 0.9 (0.87–0.94), p < 0.01; for every unit increase in BMI]. AA women had slightly but significantly higher odds of low BMD compared to Whites [OR 1.015 (1.007–1.14), p <0.01 for every unit increase in BMI]. This effect was not observed when Hispanic women were compared to Whites. There is thus a race-dependent effect of BMI on BMD. With each unit increase in BMI, BMD increases for White women, while a slight but significant decrease in BMD occurs in African American women

The case for low carbohydrate diets in diabetes management

Abstract A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (<30 g/day) cannot be recommended for a diabetic population at this time without further study. On the other hand, the dire objections continually raised in the literature appear to have very little scientific basis. Whereas it is traditional to say that more work needs to be done, the same is true of the assumed standard low fat diets which have an ambiguous record at best. We see current trends in the national dietary recommendations as a positive sign and an appropriate move in the right direction.</p

A Study to derive distribution of carotid intima media thickness and to determine its COrrelation with cardiovascular Risk factors in asymptomatic nationwidE Indian population (SCORE-India)

Background: There is presently no data to describe normal distribution of carotid intima-media thickness (CIMT), an established measure of subclinical atherosclerosis, in Indian subjects. Methods: In this multi-centric study, 1229 subjects with age ≥30 years and no previous cardiovascular disease (CVD) underwent CVD risk factor assessment and CIMT measurement. Mean far wall common carotid artery IMT was measured on both sides and averaged. Results: Mean age of the subjects was 48.0 ± 12.0 years and 54.2% were men. CIMT measurement was feasible in 1157 subjects. Mean, median and 75th percentile values of CIMT for different age-groups were derived for men and women separately. There was a progressive increase in CIMT with increasing age (P < 0.001) and men had higher CIMT values than women (0.608 ± 0.12 mm vs. 0.579 ± 0.11 mm, P < 0.001). The CIMT values were also higher in diabetics (0.635 ± 0.10 mm) and hypertensives (0.624 ± 0.10 mm) as compared to non-diabetics (0.589 ± 0.12 mm, P < 0.001) and non-hypertensives (0.592 ± 0.12, P 0.02) respectively. Among continuous variables, age, systolic blood pressure and fasting blood glucose had strong to modest correlation with CIMT (Pearson's r 0.524, 0.282 and 0.192 respectively, all P values <0.001), whereas body mass index, diastolic blood pressure and serum triglycerides exhibited weak but still statistically significant relationship (Pearson's r 0.069, P 0.019; Pearson's r 0.065, P 0.026; and Pearson's r 0.094, P 0.001, respectively). Conclusions: This is the first study to provide age- and gender-specific distribution of CIMT in Indian subjects free from CVD. This information should help facilitate further research and clinical work involving CIMT in India