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Biomedical subjects

Maria Rosaria Manigrasso

Publications and source records attributed to Maria Rosaria Manigrasso.

5 recordsLinked to original sources

Insulin resistance as a determinant of platelet activation in obese women.

OBJECTIVES: We tested the hypothesis that insulin resistance, per se, contributes to increased platelet activation in obesity, independently of underlying inflammation. BACKGROUND: Obesity, insulin resistance, and atherosclerosis are closely linked phenomena associated with low-grade inflammation. Obesity is associated with persistent platelet activation in otherwise healthy women. METHODS: We performed a cross-sectional study in 40 obese and 20 non-obese healthy women using urinary thromboxane metabolite excretion as a non-invasive index of platelet activation. An index of insulin sensitivity, S(I), and plasma adiponectin, C-reactive protein (CRP), and CD40 ligand (CD40L) levels were measured. RESULTS: Obese women had significantly (p < 0.0001) higher 11-dehydro-thromboxane B2 (11-dehydro-TXB2) excretion (median 718 vs. 211 pg/mg creatinine), CRP (1.13 vs. 0.48 mg/l), and CD40L levels (4.45 vs. 0.90 ng/ml) than controls. Obese women had lower S(I) (median 2.51 vs. 5.0 10(4) min(-1)/[microU/ml], p < 0.002) and adiponectin (6.3 vs. 10 microg/ml, p < 0.01) than control subjects. On multiple regression analysis, waist-to-hip ratio (beta = 0.27, p < 0.05) and S(I) (beta = -0.72, p < 0.04) predicted 11-dehydro-TXB2 excretion rate, independently of adiponectin, CRP, CD40L, and lipid patterns. In order to investigate the cause-effect relationship of these associations, we examined the effects of a 12-week weight loss program or a 3-week pioglitazone treatment on urinary 11-dehydro-TXB2 in 10 women with impaired S(I) and visceral obesity. Successful weight loss (0.6 kg loss/week) achieved in 5 subjects was associated with increased S(I) (+92%) and decreased CD40L (-27%), CRP (-37%), and 11-dehydro-TXB2 (-53%) (p < 0.05). Consistently, improvement of insulin sensitivity achieved with pioglitazone significantly decreased urinary 11-dehydro-TXB2 excretion (-43%, p < 0.05) without changes in body weight. CONCLUSIONS: Insulin resistance is a major determinant of platelet activation in female obesity.

Adult↗

Associations between hypertriglyceridemia and serum ghrelin, adiponectin, and IL-18 levels in HIV-infected patients.

HIV-related metabolic abnormalities include hypertriglyceridemia, hypercholesterolemia, insulin resistance, and diabetes mellitus. Recent studies suggest a role of ghrelin in promoting the deposition of triglycerides (TG) in the liver and regulating the metabolic action of adiponectin. Visceral fat is a key regulator of inflammation and it secretes proinflammatory cytokines (eg, interleukin-18, IL-18), with potential atherogenic activity. The aim of this study was to assay serum concentrations of ghrelin, adiponectin, and IL-18 in HIV+ patients, with and without hypertriglyceridemia, who were receiving highly active antiretroviral therapy (HAART). The 49 HIV+ patients were divided in 2 groups: 17 patients with serum TG concentration >200 mg/dl (group A) and 32 patients with normal serum TG concentration (group B). All subjects underwent viral and immunological evaluations and determinations of serum cholesterol, glucose, ghrelin, adiponectin, and IL-18. No differences of viral and immunological parameters were observed between the 2 groups. Serum levels of ghrelin were 768 +/- 596 pg/dl in group A and 470 +/- 248 pg/dl in group B (p = 0.01). Group A had lower serum adiponectin levels (8.4 +/- 3.6 microg/dl) than group B (18.2 +/- 10.1 microg/dl; p = 0.0001). Serum IL-18 levels were 455 +/- 199 pg/ml in group A and 258 +/- 233 pg/ml in group B (p = 0.005). The patients with hypertriglyceridemia showed a positive correlation between serum triglyceride and ghrelin levels (r = 0.51, p = 0.03). These findings suggest potential roles of ghrelin, adiponectin, and IL-18 in the pathogenesis of metabolic disorders in HIV-infected patients.

Adiponectin↗

Association of inflammation markers with impaired insulin sensitivity and coagulative activation in obese healthy women.

Insulin resistance is associated with a low chronic inflammatory state. In this study we investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. We examined 32 healthy obese women (body mass index > or = 28), with normal insulin sensitivity (NIS, n = 14) or impaired insulin sensitivity (n = 18), and 10 nonobese women (body mass index < 25). Impaired insulin sensitivity patients had significantly higher levels of C-reactive protein (CRP), TGF-beta 1, plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragment 1 + 2 (F1 + 2) compared with either control subjects or NIS patients. On the other hand, NIS patients had higher CRP, TGF-beta 1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-beta 1, CRP, PAI-1, factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-beta 1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-beta 1 and the insulin sensitivity index were independently related to F1 + 2. Our results are the first to document an in vivo relationship between insulin sensitivity and coagulative activation in obesity. The elevated TGF-beta 1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease.

Adult↗

New medical licensing examination using computer-based case simulations and standardized patients.

PURPOSE: To evaluate a new method, used for the first time in Italy, of administering the Medical Licensing Examination (MLE). METHOD: Eighty medical school graduates taking the MLE were studied. The MLE was based on the Multimedia Integrated Pilot Project (MIPP), a single two-step examination that combines computer-based case simulations (step 1) and clinical encounters using standardized patients (step 2). Step 1 assessed mainly clinical knowledge and decision-making skills. Step 2 measured the ability to obtain a focused history, perform a relevant physical examination, prioritize a differential diagnosis and management plan, and provide patient education or counseling. The correlations between the total MIPP scores and the exam scores students obtained during the six-year medical school curriculum were evaluated. RESULTS: The step 1, step 2, and total MIPP scores were moderately correlated with the curriculum scores. A moderate correlation also existed between the scores reported in step 1 and those of step 2. CONCLUSIONS: The MIPP is a good tool for assessing clinical competence. Internationally, computer-based and standardized patient assessments are being used more often in licensing examinations. Continuous use of this method could improve medical graduates' performances.

Clinical Competence↗

[The "problem obesity": viewpoint of the internist].

The prevalence of obesity has reached epidemic dimension in industrialized countries and it is known that obesity is associated with increased risk of cardiovascular morbidity and mortality. Commonly, obesity is defined by the Body Mass Index (BMI). However, BMI fails to consider body fat distribution. The relationship between the risk of metabolic-cardiovascular diseases and body fat distribution indices such as the waist-to-hip ratio (WHR) and the waist circumference, rather than measures of the degree of body fatness as expressed by BMI, has long been recognized. Recently, clinical and epidemiological research has found waist circumference to be the best anthropometric indicator of both total body fat and intra-abdominal fat mass. Android or visceral obesity is associated with metabolic syndrome and increased cardiovascular morbidity and mortality through a variety of molecular mechanisms possibly linking the metabolic syndrome to hemostatic and vascular abnormalities. Obesity guidelines suggest the need for weight reduction using behavioural change to reduce caloric intake and increasing physical activity. A realistic goal for weight reduction is to reduce body weight by 5% to 10% over a period of 6 to 12 months. Combined intervention of a low calories diet, increased physical activity, and behaviour therapy provides better outcomes for long-term weight reduction and weight maintenance than programs that use only one or two of these modalities. The drugs used to promote weight loss have been anorexic drugs or appetite suppressants. All classes of anorexic drugs affect neurotransmitters in the brain. The new agent sibutramine has norepinephrine and serotonin effects. Another new agent, orlistat, has a different mechanism of action, the reduction of fat absorption. Weight loss drugs approved by the FDA for long-term use may be useful as an adjunct to diet, physical activity and behaviour therapy for patients with a BMI of > or =30 with no concomitant obesity-related risk factors or diseases, and for patients with a BMI of > or =27 with concomitant obesity-related risk factors or diseases.

Anti-Obesity Agents↗