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Abstracts

LE Magazine August 2005
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Women and heart disease

Prevention of coronary heart disease: a nonhormonal approach.

Coronary heart disease (CHD) is a common and serious health problem facing women as they move beyond the reproductive years. Until recently, many postmenopausal women and their physicians relied heavily on hormone therapy to prevent cardiovascular disease, neglecting the well-recognized nonhormonal aspects of cardiovascular health. Simple lifestyle changes— exercise, diet, weight control, and avoidance of tobacco—can significantly reduce the chance of heart disease and its major risk factors, which are essentially the same for men and women. As with men, obesity, hypertension, hyperlipidemia, and diabetes are the major risk factors for heart disease in women. This review discusses the epidemiologic studies linking these risk factors to CHD in women, the guidelines for screening, and a brief overview of treatment recommendations.

Semin Reprod Med. 2005 May;23(2):157-66

Risk factors for coronary heart disease among inpatients who have mild intellectual disability and mental illness.

BACKGROUND: Coronary heart disease (CHD) is a major cause of morbidity and mortality in the UK. The aim of this study was to screen inpatients with mild or borderline intellectual disability, many of whom also have mental illness, for risk factors for CHD. METHODS: Cross sectional survey. Participants were interviewed, measured and had blood samples taken. RESULTS: Of the 53 participants, 20 (37.7%) were overweight and 18 (34.0%) obese. The mean body mass index (BMI) of those participants prescribed regular antipsychotics was higher than those who were not. Nine (20.9%) had waist circumference measurements placing them at increased risk of CHD and 21 (48.8%) were at substantially increased risk. Twenty-eight (52.8%) were current smokers. Of the 49 participants who had their blood pressure measured, 3 (6.1%) had readings above the reference range. Of the 19 participants who had random blood tests, one (5.3%) had an elevated cholesterol level. CONCLUSIONS: In this population there was a high prevalence of two risk factors for CHD (obesity and smoking), requiring ongoing monitoring and long-term measures to reduce risk.

J Intellect Disabil Res. 2005 May;49(Pt 5):309-16

Streptokinase—a clinically useful thrombolytic agent.

A failure of hemostasis and consequent formation of blood clots in the circulatory system can produce severe outcomes such as stroke and myocardial infraction. Pathological development of blood clots requires clinical intervention with fibrinolytic agents such as urokinase, tissue plasminogen activator and streptokinase. This review deals with streptokinase as a clinically important and cost-effective plasminogen activator. The aspects discussed include: the mode of action; the structure and structure-function relationships; the structural modifications for improving functionality; recombinant streptokinase; microbial production; and recovery of this protein from crude broths.

Biotechnol Adv. 2004 Feb;22(4):287-307

Antioxidants

Intake of alpha-tocopherol is limited among US adults.

OBJECTIVE: To examine alpha-tocopherol intake and food sources of alpha-tocopherol in the US population relative to current Dietary Reference Intakes for vitamin E. DESIGN: We analyzed food source and intake data from the 1994 to 1996 Continuing Survey of Food Intakes by Individuals (CSFII) with added values for alpha-tocopherol from the US Department of Agriculture National Nutrient Database for Standard Reference Release 15. SUBJECTS: Data from 5,056 men and 4,703 women aged 20 years and older were obtained from the 1994 to 1996 CSFII. STATISTICAL ANALYSES PERFORMED: The complex design and sampling weights of the CSFII survey were taken into account to calculate the mean alpha-tocopherol intake from diet, the SEM, and the percent of the Estimated Average Requirements (EARs) for alpha-tocopherol intake by age group and region. RESULTS: Only 8.0% of men and 2.4% of women in the United States met the new EARs for vitamin E intake from foods alone. Regionally, only 5.8% of men and 2.1% of women in the South met these EARs, relative to 9.0% and 2.6%, respectively, in the Northeast. Top contributors of alpha-tocopherol for men and women included ready-to-eat cereal, sweet baked products, white bread, beef, oils, and salad dressing. APPLICATIONS/CONCLUSIONS: The majority of men and women in the United States fail to meet the current recommendations for vitamin E intake. Many of the top contributors are not particularly high sources of alpha-tocopherol but are consumed frequently. Greater inclusion of sources such as nuts, seeds, and vitamin E-rich oils, could improve intake of alpha-tocopherol.

J Am Diet Assoc. 2004 Apr;104(4):567-75

Oxidative stress and neuroinflammation in Alzheimer’s disease and amyotrophic lateral sclerosis: common links and potential therapeutic targets.

Many neurological diseases, including Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), are now recognized to share atypical inflammatory reactions as a major pathological feature. Neuroinflammation can both be a cause, and a consequence, of chronic oxidative stress. Cytokine-stimulated microglia generate copious amounts of reactive oxygen and reactive nitrogen species, creating a stress upon ambient neurons. Conversely, oxidants can stimulate pro-inflammatory gene transcription in glia, leading to various inflammatory reactions. This review compares literature regarding neuroinflammation in AD and ALS, with special emphasis on roles played by tumor necrosis factor alpha (TNFalpha) and aberrant arachidonic acid metabolism in the genesis of chronic oxidative conditions. Based on our observations made in the G93A-SOD1 mouse model of ALS, and a body of Alzheimer’s disease findings, we hypothesize a prominent pathological role for the TNFalpha-signaling axis and neuroinflammation in the pathogenesis of both diseases. A discussion is maderegarding the relevance of neuroinflammation to potential therapeutic implications for both ALS and AD.

J Alzheimers Dis. 2004 Apr;6(2):147-57

The combined effect of transferrin saturation and low density lipoprotein on mortality.

BACKGROUND AND OBJECTIVES: Evidence suggests that cardiovascular disease (CVD) is accelerated by the oxidation of low-density lipoprotein (LDL) in the presence of iron. This study examined whether adults with elevated iron, as measured by transferrin saturation (TS), and elevated LDL are at an increased risk for mortality. METHODS: This is a cohort study of the adult US population using the National Health and Nutrition Examination Survey 1976-1980 (NHANES II) merged with the NHANES II Mortality Study in 1992. Multivariate Cox regression was performed to determine hazard ratios (HR) for CVD and all-cause mortality for high (>55%) or low (<55%) levels of TS and high (>160 mg/dl) or low (<160 mg/dl) levels of LDL. RESULTS: An elevated LDL alone did not significantly increase CVD mortality or all-cause mortality in the adjusted model. Individuals with elevated LDL and elevated TS had a statistically significant increase in both CVD mortality and all-cause mortality (HR=5.74 and 3.53, respectively) compared to the low LDL and low TS group. CONCLUSIONS: The results of this study indicate an increased risk associated with the combination of elevated LDL and elevated TS, which suggests that iron-mediated oxidation of LDL may be a significant factor in the progression of CVD.

Fam Med. 2004 May;36(5):324-9

Copper mediates dityrosine cross-linking of Alzheimer’s amyloid-beta.

We have previously reported that amyloid Abeta, the major component of senile plaques in Alzheimer’s disease (AD), binds Cu with high affinity via histidine and tyrosine residues and produces H(2)O(2) by catalyzing the reduction of Cu(II) or Fe(III). Incubation with Cu induces the SDS-resistant oligomerization of Abeta, a feature characteristic of neurotoxic soluble Abeta extracted from the AD brain. Since residues coordinating Cu are most vulnerable to oxidation, we investigated whether modifications of these residues were responsible for Abeta cross-linking. SDS-resistant oligomerization of Abeta caused by incubation with Cu was found to induce a fluorescence signal characteristic of tyrosine cross-linking. Using ESI-MS and a dityrosine specific antibody, we confirmed that Cu(II) (at concentrations lower than that associated with amyloid plaques) induces the generation of dityrosine-cross-linked, SDS-resistant oligomers of human, but not rat, Abeta peptides. The addition of H2O2 strongly promoted Cu-induced dityrosine cross-linking of Abeta1-28, Abeta1-40, and Abeta1-42, suggesting that the oxidative coupling is initiated by interaction of H2O2 with a Cu(II) tyrosinate. The dityrosine modification is significant since it is highly resistant to proteolysis and is known to play a role in increasing structural strength. Given the elevated concentration of Cu in senile plaques, our results suggest that Cu interactions with Abeta could be responsible for causing the covalent cross-linking of Abeta in these structures.

Biochemistry. 2004 Jan 20;43(2):560-8

Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models.

Curcumin is a polyphenolic diketone from turmeric. Because of its anti-oxidant and anti-inflammatory effects, it was tested in animal models of Alzheimer’s disease, reducing levels of amyloid and oxidized proteins and preventing cognitive deficits. An alternative mechanism of these effects is metal chelation, which may reduce amyloid aggregation or oxidative neurotoxicity. Metals can induce Abeta aggregation and toxicity, and are concentrated in AD brain. Chelators desferrioxamine and clioquinol have exhibited anti-AD effects. Using spectrophotometry, we quantified curcumin affinity for copper, zinc, and iron ions. Zn2+ showed little binding, but each Cu2+ or Fe2+ ion appeared to bind at least two curcumin molecules. The interaction of curcumin with copper reached half-maximum at approximately 3-12 microM copper and exhibited positive cooperativity, with Kd1 approximately 10-60 microM and Kd2 approximately 1.3 microM (for binding of the first and second curcumin molecules, respectively). Curcumin-iron interaction reached half-maximum at approximately 2.5-5 microM iron and exhibited negative cooperativity, with Kd1 approximately 0.5-1.6 microM and Kd2 approximately 50-100 microM. Curcumin and its metabolites can attain these levels in vivo, suggesting physiological relevance. Since curcumin more readily binds the redox-active metals iron and copper than redox-inactive zinc, curcumin might exert a net protective effect against Abeta toxicity or might suppress inflammatory damage by preventing metal induction of NF-kappaB.

Alzheimers Dis. 2004 Aug;6(4):367-77

Alpha-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats.

Several lines of evidence have suggested that triglyceride accumulation in skeletal muscle and pancreatic islets is causally related to type 2 diabetes mellitus. We recently showed that alpha-lipoic acid (ALA), a potent antioxidant and cofactor of mitochondrial respiratory enzymes, reduces body weight of rodents by suppressing food intake and increasing energy expenditure. We sought to determine if ALA can prevent the development of diabetes mellitus in obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Most (78%) untreated OLETF rats showed glycosuria at 40 weeks of age, but this was completely prevented by ALA. Compared with untreated OLETF rats, ALA reduced body weight and protected pancreatic beta-cells from destruction. ALA also reduced triglyceride accumulation in skeletal muscle and pancreatic islets. These results indicate that ALA prevents diabetes mellitus in obese diabetes-prone rats by reducing lipid accumulation in non-adipose tissue as well as in adipose tissue.

Biochem Biophys Res Commun. 2005 Jan 7;326(1):197-2

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