Mohamad H. Horani

Effect of Diabetes on the blood brain barrier

Diabetes mellitus is a metabolic disorder associated with structural and functional alteration of various organ systems including the central nervous system. The overall evidence suggests that the effect of Diabetes mellitus on the brain, although more subtle than some other chronic diabetic complications, is appreciable. A variety of pathogenetic mechanisms contribute to the central nervous system dysfunction in diabetic patient population. One major contributor is the Diabetes related alterations in the function of the blood-brain barrier (BBB). These alterations can be found in both barrier and transport components of the BBB function and can be attributed to changes in physicochemical properties of the endothelial cell membranes and of the tight junctions of the cerebral microvasculature. The present communication briefly reviews the Diabetes-related changes in the central nervous system and discusses some of the mechanisms underlying these changes.

Seroprevalence of viral hepatitis in an older nursing home population

OBJECTIVES: To assess the prevalence of current or previous infection with viral hepatitis agents in an older nursing home population.

Management of Obesity in the Elderly

Over the last few decades, there has been an unprecedented increase in the prevalence of obesity, especially in economically developed countries. Furthermore, it is becoming an increasingly recognized health problem in the elderly.The precise mechanisms underlying increased adiposity in the elderly are not known. Aging is associated with a host of biologic changes that limit the ability of the individual to regulate energy homeostasis. Thus, it is likely that older individuals may be more likely to develop the two extremes of the spectrum of nutritional abnormalities, namely malnutrition and increased adiposity. These nutritional abnormalities are associated with significant morbidity and mortality. Current guidelines define overweight as a body mass index (BMI) of 25–29.9 kg/m2 and obesity as a BMI of 30 kg/m2 or more. However, the optimal BMI may be different in older individuals.Management strategies should attempt to optimize the nutritional status of older individuals. Age per se cannot be used as a justification for denying medical management of obesity to elderly individuals. Individualized programs with the goal of achieving modest weight reduction in obese patients are likely to result in immediate (e.g. alleviation of arthritic pains and reduction of glucose intolerance) and possibly long-term (e.g. reduction in cardiovascular risk) healthcare benefits. Management should emphasize lifestyle modifications, while the use of pharmacologic agents such as sibutramine and orlistat should be reserved for select groups of patients who do not respond to lifestyle modification.

Effect of Chromium on Apolipoprotein A-I Expression in HepG2 Cells

OBJECTIVE Chromium is a key micronutrient required for lipid and carbohydrate metabolism. Some but not all clinical trials have associated use of chromium supplements with improved insulin sensitivity and lipid profile including increased high-density lipoprotein cholesterol levels. METHODS Because apolipoprotein A-I (apoA-I) is the principal protein of high-density lipoprotein, the molecular pathways underlying chromium-related changes in apoA-I expression were studied in a human hepatoma cell line (HepG2) transfected with full-length apoA-I promoter attached to the reporter chloramphenicol acetyl transferase gene. RESULTS Exposure of these cells to different concentrations of chromium chloride (0, 0.5, 1.0, and 3.0 mM) resulted in a dose-dependent decrease in apoA-I promoter activity (chloramphenicol acetyl transferase activity expressed as a percentage of an internal control was 99.4 +/- 7.2% in control cells versus 87.6 +/- 5.0%, 73.4 +/- 2.3%, and 36.6 +/- 3.9%, respectively, P < 0.01). Chromium chloride at 10 mM concentration was toxic and caused death in a large number of cells. Treating HepG2 cells with other minerals known to have insulin-sensitizing effects such as magnesium (1 mM), zinc (0.2 mM), and vanadyl sulfate (0.1 mM) significantly reduced apoA-I promoter activity in the presence and absence of 100 microU/mL of insulin. Northern blot analyses showed that the apoA-I mRNA content of cells treated with 0.2 mM of chromium chloride relative to G3PDH mRNA was not significantly increased compared with controls (0.652 +/- 0.122 versus 0.745 +/- 0.143, the ratio of apoA-I to glyceraldehyde 3-phosphate dehydrogenase (G3PDH) mRNA in control and chromium-treated cells, respectively). Western blot analyses of proteins secreted in culture media indicated that neither chromium treatment of the HepG2 cells (858.0 +/- 151.4 arbitrary units) nor treatment with magnesium (1323.3 +/- 175.7) or vanadium (1102 +/- 78.7) significantly altered apoA-I concentrations compared with controls (1061.7 +/- 114.7). However treatment of HepG2 cells with 0.2 mM of zinc significantly reduced apoA-I concentrations (291.0 +/- 29.2 versus 1061.7 +/- 114.7; P < 0.001). CONCLUSIONS Supraphysiologic concentrations of chromium and other minerals with known insulin-sensitizing activity may reduce apoA-I promoter activity in cultured cells. Whether similar changes may occur in vivo remains to be shown. However, these observations do not support the use of pharmacologic amounts of chromium supplementation to enhance the cardioprotective lipid profile.

Suppression of hyperglycemia-induced superoxide formation and endothelin-1 gene expression by carvedilol.

Carvedilol (CV) is a beta-blocker with favorable effects on cardiovascular disease. To determine whether CV can prevent increases in superoxide (SO) production due to hyperglycemia, human umbilical vein endothelial cells (HUVEC) were treated with either 100 or 500 mg/dL dextrose in the presence or absence of 0.1, 1.0, and 10 μmol/L CV. Superoxide levels were measured using the hydroethidine (HE) fluorescence method. Generation of SO was linear from time 0 to 60 minutes. At 60 minutes, the HE fluorescence in cells treated with 500 mg/dL dextrose (123.3 ± 4.9 units) was significantly higher than that in control cells treated with 100 mg/dL dextrose (84.0 ± 3.5 units) (P < 0.002). Addition of 0.1, 1.0, and 10 μmol/L CV to cells treated with 500 mg/dL dextrose decreased SO generated to 113.3 ± 1.8, 98.7 ± 8.3, and 70.0 ± 1.0 units, respectively (P < 0.13, P < 0.05, and P < 0.004, respectively). Cellular endothelin-1 mRNA and endothelin-1 protein secreted in culture media were significantly increased in the presence of 500 mg/dL dextrose. The addition of 10 μmol/L CV significantly decreased both endothelin-1 (1-21) mRNA and protein levels. Measurements of media lactate dehydrogenase activity indicated that CV inhibited cytotoxicity caused by 500 mg/dL dextrose. These findings suggest that CV not only prevents dextrose-induced SO generation in endothelial cells but may also have favorable effects on gene expression and cell survival.

Home Hospitalization Service for Acute Uncomplicated First Ischemic Stroke in Elderly Patients

1. Disability and functional impairment, using the activity of daily living (ADL) scale and the seven-item Functional Impairment Measure. 2. Mental status and severity of stroke-related neurologic deficit using the Canadian Neurological Scale and modified National Institutes of Health Stroke Scale. 3. Depression using the Geriatric Depression Scale (GDS). Patients were evaluated at baseline and after 6 months.

Dehydroepiandrosterone and Pregnenolone

Steroid hormones play a multifactorial role in human physiology. They facilitate coordinative processes that enable neural, endocrine, immune, and metabolic systems, separately or collectively, to operate in solving problems of survival and reproduction. Both pregnenolone and dehydroepiandrosterone (DHEA) are key hormones early in the pathway of steroid hormones biosynthesis (Fig. 1). Actually, pregnenolone is the precursor of all the known steroid hormones, and its formation from cholesterol via the action of cytochrome P450scc, is the rate limiting step in steroid hormone formation. DHEA and its sulfated conjugate, dehydroepiandrosterone sulfate (DHEAS), on the other hand, serve as precursors for both androgenic and estrogenic steroids, and are the most abundant steroid hormones in the human body. The plasma levels of both DHEA and pregnenolone have been shown to decline progressively with advancing age. Furthermore, based on multiple animal and human studies, there is now accumulating evidence to suggest a potential role for both these hormones in the prevention of multiple morbidities associated with the aging process. This chapter reviews the biological roles of DHEA and pregnenolone and draws implications for their possible role as antiaging agents.