Death by a Thousand Cuts: Stress Exposure and Black-White Disparities in Physiological Functioning in Late Life.

OBJECTIVES: This paper investigates Black-White differences in stress-including diverse measures of chronic, acute, discrimination-related, and cumulative stress exposure-and examines whether race differences in these stress measures mediate Black-White disparities in C-reactive protein (CRP) and metabolic dysregulation in later life. METHODS: Using data from the Health and Retirement Study (HRS) (2004-2012), this study uses stepwise ordinary least squares (OLS) regression models to examine the prospective associations between multiple stressors-including traumatic and stressful life events, financial strain, chronic stress, everyday and major life discrimination, and measures of cumulative stress burden-and CRP and metabolic dysregulation. Mediation analyses assessed the contribution of stress exposure to Black-White disparities in the outcomes. RESULTS: Blacks experienced more stress than Whites across domains of stress, and stress exposure was strongly associated with CRP and metabolic dysregulation. Race differences in financial strain, everyday and major life discrimination, and cumulative stress burden mediated Black-White gaps in the outcomes, with measures of cumulative stress burden mediating the greatest proportion of the racial disparities. DISCUSSION: The "thousand cuts" that Blacks experience from their cumulative stress exposure across domains of social life throughout the life course accelerate their physiological deterioration relative to Whites and play a critical role in racial health disparities at older ages.

Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes.

INTRODUCTION: The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). AIM OF THE STUDY: Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. MATERIALS AND METHODS: The study consisted of 138 patients aged 5-18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p < 0.05. RESULTS: The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. CONCLUSIONS: Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.

Assessment of Dietary Patterns Represents a Potential, Yet Variable, Measure of Inflammatory Status: A Review and Update.

Chronic low-grade, systemic inflammation is a well-characterized risk factor in the development of chronic metabolic diseases, such as cardiovascular disease, type 2 diabetes, and metabolic syndrome. Diet could be an effective strategy for reducing inflammation associated with chronic disease. While anti-inflammatory properties of isolated dietary bioactive and functional foods have been routinely studied, the evaluation of dietary patterns on inflammation warrants further review-especially given the recent inclusion of dietary pattern recommendations into dietary guidelines and policies. Therefore, the objective of this narrative review is to examine current evidence linking diet to low-grade, systemic inflammation within the context of chronic disease. Specifically, we provide an update on the findings from human trials that have characterized anti-inflammatory properties of dietary patterns, defined by various methods and indexes. Given the complexity of interpreting results from dietary pattern analysis, we further present recent evidence on the anti-inflammatory roles of isolated bioactive nutrients and functional foods that are common components of distinct dietary patterns, in addition to considerations for interpreting dietary pattern research, population-specific dietary recommendations, and future studies. Overall, we observe a vast range of variability in the evidence from observational studies that have evaluated the relationships between healthy dietary patterns and inflammatory markers. These studies highlight the need for additional intervention studies with study designs that account for metabolic status, diversity in populations, breadth of inflammatory measurements, fasting vs. postprandial effects of diet, and control of confounding factors (e.g., genotype, microbiome profiles, and dietary adherence) in order to better understand the effect that diet has, as a whole, on inflammation. These strategies will help to strengthen diet recommendations aimed at reducing inflammation and chronic disease risk.

Functional and endocrine-metabolic oligomenorrhea: proposal of a new diagnostic assessment tool for differential diagnosis in adolescence.

Background To develop a diagnostic assessment tool, using clinical, biochemical and sonographic markers, to help clinicians in the differential diagnosis of functional oligomenorrhea (FO) and endocrine-metabolic oligomenorrhea (EMO). Methods Sixty-two adolescents with oligomenorrhea without evident hormonal imbalances or severe energy deficit were selected. They were divided into two groups (EMO and FO) and they all underwent the following assessment: physical examination (height, weight, presence of hirsutism or acne), blood exams and transabdominal ultrasonography. The biochemical markers included: hemoglobin, thyrotropin stimulating hormone (TSH), prolactin (PRL), follicle stimulating hormone (FSH), luteinizing hormone (LH), free (FT) and total testosterone (TT), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG). Uterine and ovarian volume, ovarian morphology, endometrial thickness and pulsatility index (PI) of uterine arteries were evaluated with ultrasound. Results Body mass index (BMI), hemoglobin, LH levels and LH/FSH ratio were significantly higher in women with EMO than in those with FO. Increased androgens values were found in the EMO group, but only A and FT were significantly different (p=0.04). Ovarian volume and uterine artery PI were the only ultrasound features significantly different, with higher values in the EMO population (p<0.05). Considering these variables, with a receiving characteristic operating curve, new cut-offs were calculated, and a diagnostic assessment tool elaborated (area under curve [AUC] 0.88, specificity 99%, sensibility 59%, p<0.001]. Conclusions This diagnostic tool, specific for adolescents, could be useful in the management of oligomenorrhea. Recognizing and distinguishing EMO and FO is very important in order to establish an appropriate treatment and a correct follow-up.

Socioeconomic inequalities in the prevalence of biomarkers of cardio-metabolic disease in South Korea: Comparison of the Health Examinees Study to a nationally representative survey.

BACKGROUND/OBJECTIVES: This study aimed to examine socioeconomic inequalities in the prevalence of biomarkers of cardiovascular disease and diabetes in the newly developed large-scale genomic cohort study of Korean adults, the Health Examinees-Gem (HEXA-G), with a comparison of the nationally representative cross-sectional study, the Korea National Health and Nutrition Examination Survey (K-NHANES). SUBJECTS/METHODS: Using the HEXA-G and the K-NHANES from 2007-2012, we analyzed the age-adjusted relative risk (RR) and prevalence of enlarged waist circumference (EWC), elevated triglycerides (ET), low HDL cholesterol (LHC), elevated blood pressure (EBP) and elevated blood glucose (EBG) by income and educational groups for adults at age 40-69. RESULTS: For men, the prevalence of risk factors was similar across different income and educational groups (p>0.1), and between the K-NHANES and the HEXA-G. Among five risk factors, EBG showed the greatest discrepancy by 7 to 11 percentage points (i.e., the prevalence of 0.43 and 0.36 for college graduates, respectively, in K-NHANES and HEXA-G). For women, socioeconomic inequalities appeared for the five risk factors. Prevalence of risk factors was mostly lower in the HEXA-G than the K-NHANES, by approximately 11.0 percentage points. Especially, the discrepancy between K-NHANES and HEXA-G was largest in EBG (i.e., the prevalence of 0.31 and 0.20 for the lowest income groups, respectively). CONCLUSION: The HEXA-G shows broadly similar socioeconomic inequality in prevalence of cardio-metabolic risk factors to the nationally representative sample with more modest socioeconomic inequality among women in the HEXA-G than the K-NHANES.

Polycystic ovarian syndrome: Assessment of approaches to diagnosis and cardiometabolic monitoring in UK primary care.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age. We examined the specific tests that are done in primary care to lead to the diagnosis of PCOS, and to support the diagnosis once made. METHODS: One thousand seven hundred and ninety-seven women were identified from a pooled GP practice database. The search included all patients defined with PCOS or related terms. Records included demographic information, medical history (diagnoses), blood test results and whether a pelvic ultrasound scan had been performed. RESULTS: The most common age of PCOS diagnosis was 20-29 years; 67.7% of the women had at least one concomitant Read-coded diagnosis. Most pelvic ultrasound scans were performed in the month immediately prior to diagnosis. In the 12 months prior to the diagnosis of PCOS being made, 30.5% of women underwent a measurement of their serum total testosterone level while 29.6% had their serum SHBG measured. For serum oestradiol, the corresponding statistics were 28.4%, LH 45.3% and for FSH 45.5% checked before diagnosis. Fasting blood glucose, random glucose and HbA1c were checked in 10.2%, 18.8% and 4.2%, of women before diagnosis, respectively, but in only 7.9%, 6.0% and 3.4% of women in the 24 months after diagnosis. There was a tendency for endocrine testing (oestradiol, LH, FSH, testosterone, SHBG) to peak in the weeks before diagnosis. For plasma glucose, testing was performed more evenly over time as for serum cholesterol. Of all women diagnosed with PCOS, 32.8% were prescribed metformin, 3.7% antihypertensives, 2.2% statins and 63.5% an oestrogen-containing contraceptive pill or HRT. CONCLUSION: The underlying pathophysiology of PCOS is still not fully understood. As a result, treatment is often focused on individual symptoms, not the syndrome itself. Robust laboratory led protocols would provide the necessary information to enable an appropriate diagnostic evaluation/cardometabolic monitoring.

Clinical correlates of sex hormones in women: The study of health in Pomerania.

BACKGROUND: Despite associations of sex hormones in women with increased cardiometabolic risk and mortality, the clinical correlates of altered sex hormone concentrations in women are less clearly understood. We investigated a broad range of clinical correlates of sex hormones in women from a large population-based sample. METHODS: Data from 2560 women from two cohorts of the Study of Health in Pomerania were used. Stepwise multivariable regression models were implemented to investigate a broad range of behavioral, socio-demographic, and cardiometabolic clinical correlates related to total testosterone (TT), free testosterone (fT), androstenedione (ASD), dehydroepiandrosterone-sulfate (DHEAS), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG). RESULTS: Waist circumference and BMI (ß-coefficient: -0.03; 95% CI: -0.04; 0.03) were inversely related to SHBG, and BMI was positively related to TT (ß-coefficient: 0.005; 95% CI: 0.001; 0.009), fT, E1, and E2. Smoking was positively related to TT (ß-coefficient: 0.04; 95% CI: 0.01; 0.06), ASD, and fT. Systolic blood pressure (TT: ß-coefficient: 0.002; 95% CI: 0.001; 0.003), hypertension (TT: ß-coefficient: 0.05; 95% CI: 0.003; 0.11), low-density lipoprotein (LDL) cholesterol (TT: ß-coefficient: 0.02; 95% CI: 0.01; 0.05), and total cholesterol (TT: ß-coefficient: -0.03; 95% CI: 0.01; 0.05) were positively related to TT and ASD. Finally, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) were positively related to fT, but inversely related to SHBG. CONCLUSIONS: Our population-based study, with sex hormone concentrations measured by liquid chromatography tandem mass spectrometry, revealed associations between clinical correlates including waist circumference, smoking, cohabitation, systolic blood pressure, cholesterol, and MetS with sex hormones. Thus, sex hormones and SHBG may play a role in the cardiovascular risk profile of women.

Alteration of the growth hormone axis, visceral fat dysfunction, and early cardiometabolic risk in adults: the role of the visceral adiposity index.

The aim of the study is to clarify the relationship between adipose tissue dysfunction, metabolic profile and growth hormone (GH)/insulin-like growth factor (IGF)-I secretion in healthy adult subjects. We investigated the metabolic profile in a cohort of 231 consecutive healthy subjects in relation to GH, IGF-I levels, and visceral adiposity index (VAI). Anthropometric measures, lipid profile, and glucose and insulin levels during oral glucose tolerance test, Homa-IR and ISI Matsuda, IGF-I and GH peak after GHRH plus Arginine test were analyzed. The subjects with high VAI showed lower GH peak (22.8 ± 11.1 vs. 42.2 ± 21.3 µg/L; p = 0.049) and lower IGF-I (presented as IGF-I under normal range, UNR) (0.54 ± 0.14 vs. 0.64 ± 0.12; p = 0.005) than group with normal VAI. ROC curve analysis identified the cut-off, able to detect subjects with high VAI, i.e., 31.8 µg/L for GH peak and 0.63 for IGF-1 UNR. The subjects with GH peak and IGF-I UNR under the cut-off showed significantly higher levels of VAI, systolic and diastolic blood pressure, glucose and insulin levels, Homa-IR, and lower ISI Matsuda, with a concomitant worse lipid profile (all p < 0.001). A strong relationship between GH axis, VAI and metabolic risk has been demonstrated. A percentage of apparently healthy subjects show a degree of visceral adipose dysfunction associated with GH and IGF-I levels that do not meet the criteria of overt GH deficiency (GHD). Long-term prospective studies could help to clarify and confirm whether a hypothetical condition of subclinical GHD could be taken into account as a new clinical entity.

Telemedicine as a tool to mitigate cardiometabolic risk associated with serious mental illness.

People with serious mental illness suffer from substantially higher rates of cardiometabolic morbidity and mortality than the general population. We have evaluated the efficacy of telemedicine for providing cardiometabolic risk management services compared to in-person care. A retrospective chart review was conducted in order to compare changes in body mass index (BMI), systolic blood pressure and serum triglycerides before and after telemedicine (n=38). The comparator group (n=38) was selected from a list of all clients who had a conventional appointment at the metabolic clinic. Analysis of Variance showed an overall effect of treatment on BMI (P<0.001), but no significant differences between the groups on BMI (P=0.89), systolic blood pressure (P=0.62) or fasting serum triglycerides (P=0.81). This suggests that telemedicine may be as effective as in-person care and that telemedicine has the potential to improve access to cardiometabolic risk management services for people with serious mental illness.

Vitamin D status and cardiometabolic assessment in infancy.

BACKGROUND: Infants are at risk of vitamin D insufficiency, owing to their limited exposure to direct sunlight and the low levels of vitamin D in breast milk. Although vitamin D insufficiency has been associated with cardiometabolic risk factors in children, these associations have not been studied in infants, despite their unique risks. Therefore, we sought to determine whether vitamin D status was associated with cardiometabolic measures in infants. METHODS: Ninety-nine full-term infants were evaluated at the age of 1 y with measurement of 25-hydroxy vitamin D (25-OH-D) and an array of traditional (fasting glucose, insulin, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, triglycerides) and emerging (C-reactive protein, adiponectin, leptin) cardiometabolic risk factors. On the basis of 25-OH-D levels, infants were classified as vitamin D sufficient (n = 59), vitamin D insufficient (n = 29), or vitamin D deficient (n = 11). RESULTS: Duration of exclusive breastfeeding and prevalence of nonwhite ethnicity were highest in the vitamin D-deficient group (P = 0.05 and 0.03, respectively). Current use of vitamin D supplementation was highest in the sufficient group (P = 0.02). Of note, however, there were no significant differences among the three groups in any of the cardiometabolic risk factors, on both unadjusted and covariate-adjusted analyses. CONCLUSION: Vitamin D insufficiency/deficiency is not associated with an adverse cardiometabolic risk factor profile in 1-y-old infants.

Fetuin-A does not explain ethnic disparity in cardiometabolic risk factors and subclinical atherosclerosis between Hispanics and non-Hispanic whites.

BACKGROUND: Fetuin-A has been associated with insulin resistance and inversely related with vascular calcification. The present study evaluated whether serum fetuin-A explains the ethnic disparity in the subclinical atherosclerosis and risk for diabetes between healthy Hispanic and non-Hispanic white (NHW) subjects. METHODS: Fetuin-A was measured in serum of 76 age-matched healthy males (41 NHW, 35 Hispanics). Body mass index, blood pressure, serum lipoprotein cholesterol and triglyceride levels, coronary artery calcium (CAC), fasting glucose and insulin concentrations, and plasma glucose levels 2 h after a 75-g oral glucose tolerance test were measured in all participants. Insulin resistance was estimated using the homeostasis model assessment (HOMA). RESULTS: Fasting insulin, fasting and 2-h serum glucose, and HOMA values were all significantly higher in Hispanics (p < 0.05 for all), yet CAC trended lower and the prevalence of very high CAC (>400 Agatston score) was lower (P = 0.03). There was no statistically significant difference in serum fetuin-A when comparing Hispanics and NHW (P = 0.12). Furthermore, there was no correlation between fetuin-A levels and CAC (P = 0.9). CONCLUSIONS: Serum fetuin-A concentration was not associated with measures of insulin resistance or with preclinical atherosclerosis in Hispanics and NHW. These data indicate that the disparity in prevalence of insulin resistance, type 2 diabetes, and subclinical atherosclerosis between Hispanics and NHW does not appear attributable to differences in fetuin-A concentrations.

Association between anthropometric indicators of body fat and metabolic risk markers in post-menopausal women.

OBJECTIVE: to evaluate anthropometric indicators of body fat and their association with metabolic risk markers in postmenopausal women. METHODS: A cross-sectional study with 80 Brazilian women (40-70 years) was carried out. Body mass index (BMI = weight/height(2)), waist circumference (WC) and waist-to-hip ratio (WHR) were obtained for anthropometric evaluation. Trunk fat mass (TFM) was measured by dual-energy X-ray absorptiometry. The following metabolic variables were evaluated: total cholesterol (TC), HDL, LDL, triglycerides (TG), as well as glycemia and insulin to determine insulin resistance (HOMA-IR). RESULTS: Overweight and obesity were observed in 81% of the women. Values of WC >88 cm were observed in 68.5% of the women. On average, TC, LDL and TG levels were above normal levels in 60, 50 and 42.5% of the women, respectively; and HDL was normal in 82.5%. IR was observed in 37.5% of the women. Positive correlations were found between anthropometric indicators and TFM (P < 0.05). WC was most correlated with TFM (r = 0.92), followed by BMI (r = 0.88) and by WHR (r = 0.48; P < 0.05). All anthropometric indicators and TFM showed significant negative correlations with HDL and significant positive correlations with HOMA-IR (P < 0.05). Only WHR was significantly associated with dysglycemia (R(2) = 12%), hypertriglyceridemia (R(2) = 17%) and decreased HDL (R(2) = 27%). WC was significantly associated with HOMA-IR (R(2) = 34%). CONCLUSION: WC and WHR are anthropometric measures that showed strong correlation with TFM and with metabolic risk markers in postmenopausal women.

Metabolic assessment of aripiprazole as adjunctive therapy in major depressive disorder: a pooled analysis of 2 studies.

In 2 identical multicenter, double-blind, placebo-controlled trials, an 8-week prospective treatment phase to ensure inadequate response to standard antidepressants was followed with 6 weeks of aripiprazole (2-20 mg/d) or placebo, plus a standard antidepressant. This pooled analysis involving 737 patients across the 2 studies evaluated the metabolic effects of adjunctive aripiprazole in patients with major depressive disorder. Outcomes included mean change from end of prospective treatment phase to endpoint in body weight, waist circumference, fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting plasma glucose, and glycosylated hemoglobin (hemoglobin A1C). Logistic regression determined whether baseline variables were associated with weight gain or whether weight change was associated with clinical outcome. Statistically significant increases occurred in mean body weight (adjunctive aripiprazole, +1.73 kg, vs adjunctive placebo, +0.38 kg; P < 0.001). Significantly more subjects receiving adjunctive aripiprazole had clinically relevant (> or = 7%) weight gain versus placebo (5.2% vs 0.6%; P < 0.001). More patients treated with adjunctive aripiprazole shifted body mass index category group from normal to overweight and from overweight to obese than those treated with adjunctive placebo. Body mass index, sex, age, Montgomery-Asberg Depression Rating Scale score, fasting TG, fasting glucose, and standard antidepressants were not clinically meaningful predictors of weight gain with adjunctive aripiprazole, and change in weight had no correlation with clinical outcome. Adjunctive aripiprazole produced no significant changes versus placebo in mean waist circumference, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TG, fasting plasma glucose, or hemoglobin A1C. Also, there was no apparent change in the incidence of National Cholesterol Education Program-defined abnormal metabolic measures after treatment with aripiprazole.

Prevention of non-communicable disease in a population in nutrition transition: Tehran Lipid and Glucose Study phase II.

BACKGROUND: The Tehran Lipid and Glucose Study (TLGS) is a long term integrated community-based program for prevention of non-communicable disorders (NCD) by development of a healthy lifestyle and reduction of NCD risk factors. The study begun in 1999, is ongoing, to be continued for at least 20 years. A primary survey was done to collect baseline data in 15005 individuals, over 3 years of age, selected from cohorts of three medical heath centers. A questionnaire for past medical history and data was completed during interviews; blood pressure, pulse rate, and anthropometrical measurements and a limited physical examination were performed and lipid profiles, fasting blood sugar and 2-hours-postload-glucose challenge were measured. A DNA bank was also collected. For those subjects aged over 30 years, Rose questionnaire was completed and an electrocardiogram was taken. Data collected were directly stored in computers as database software- computer assisted system. The aim of this study is to evaluate the feasibility and effectiveness of lifestyle modification in preventing or postponing the development of NCD risk factors and outcomes in the TLGS population. DESIGN AND METHODS: In phase II of the TLGS, lifestyle interventions were implemented in 5630 people and 9375 individuals served as controls. Primary, secondary and tertiary interventions were designed based on specific target groups including schoolchildren, housewives, and high-risk persons. Officials of various sectors such as health, education, municipality, police, media, traders and community leaders were actively engaged as decision makers and collaborators. Interventional strategies were based on lifestyle modifications in diet, smoking and physical activity through face-to-face education, leaflets & brochures, school program alterations, training volunteers as health team and treating patients with NCD risk factors. Collection of demographic, clinical and laboratory data will be repeated every 3 years to assess the effects of different interventions in the intervention group as compared to control group. CONCLUSION: This controlled community intervention will test the possibility of preventing or delaying the onset of non-communicable risk factors and disorders in a population in nutrition transition. TRIAL REGISTRATION: ISRCTN52588395.

Comparison of high-sensitivity C-reactive protein serum assay results obtained using Dade-Behring BNII nephelometer and Ortho Vitros FS 5.1 clinical analyzer in respect of CRP-related risk assessment of chronic metabolic diseases.

BACKGROUND: Serum concentration of high sensitive C-reactive protein (hsCRP) can predict the risk of chronic metabolic and cardiovascular diseases but it is unclear whether turbidimetric high sensitive assays of CRP are adequate. METHODS: Concentrations of serum CRP in 126 samples of serum were measured with high-sensitivity methods using nephelometry (BN II Nephelometer) and turbidimetry (Ortho Vitros FS 5.1). RESULTS: For CRP concentrations measured by nephelometry and turbidimetry intra-assay CVs were 3.2 and 0.9% at mean CRP concentrations of 1.4 and 2.1 mg/l, inter-assay CVs for commercial controls were 3.1% and 3.6% at mean concentrations of 1.3 and 1.7 mg/l, and mean biases were 7.62% and 2.26%, respectively. Measurements were strongly, linearly correlated (r = 0.99; CRP vitros = 0.03 +1.03 CRP (BN II)). When disease risk was assessed by nephelometry and turbidimetry, results were similar. If the risk of disease was classified as moderate (1.0 < CRP < or = 3.0 mg/l) or high (CRP > 3.0 mg/l), the frequency of misclassified cases was only 2.3 and 2.1%, respectively. The classification agreement weighted kappa coefficient was 0.94 (95% C.I.: 0.89-0.98). CONCLUSIONS: turbidimetric high sensitive CRP assays can properly classify CRP-related prediction of chronic metabolic diseases with special consideration on cardiovascular risk.

Fatty acid sensor for low-cost lifetime-assisted ratiometric sensing using a fluorescent fatty acid binding protein.

Elevated free fatty acid (FA) levels lead to insulin resistance, hypertension, and microangiopathy, all of which are associated with type 2 diabetes. On the other hand, deficiencies of FA are indicative of certain neurodegenerative diseases, including autism. Thus, free FA levels are a diagnostic indicator for a variety of disorders. Here we describe the use of a commercially available FA binding protein labeled with acrylodan (ADIFAB), which we modified with a ruthenium metal-ligand complex with the intention of creating a low-cost FA sensor. The dual-labeled FA binding protein was used in lifetime-assisted ratiometric sensing (LARS) of oleic acid. For both steady-state and time-resolved luminescence decay experiments, the protein is responsive to oleic acid in the range of 0.02-4.7 microM. The emission at 432 nm, which is associated with the acrylodan occupying the FA binding site, decreases in intensity and red shifts to 505 nm on the addition of oleic acid. The intensities of the 505-nm peak due to the acrylodan displaced from the binding site by FA and of the 610-nm emission peak of ruthenium remained nearly unchanged. Fitting of the fluorescence decay data using the method of least squares revealed three emitting components with lifetimes of approximately 0.60, 4.00, and 370 ns. Fractional intensities of the emitting species indicate that changes in modulation between 2 and 10 MHz on binding of the protein with oleic acid are due mainly to the 4.00-ns component. The 0.60- and 370-ns components are assigned to acrylodan (505 nm) and ruthenium, respectively. Note that because ruthenium has a lifetime that is two orders of magnitude longer than that of acrylodan, the FA measurements were carried out at excitation frequencies lower than what can be done with acrylodan alone. Thus, low-cost instrumentation can be designed for a practical FA sensor without sacrificing the quality of measurements.

[Assessment of postload glycemic curves in the prediction of carbohydrate metabolic disturbances in patients with bronchial asthma].

The sensitivity and responses to exogenous insulin were studied in 78 patients with bronchial asthma. The study identified 6 types of postinsulin blood glucose concentration curves that reflected hormonal control impairments of different phases. Decreased insulin sensitivity, a delayed biological effect, and insulin resistance may serve as the early predictors of carbohydrate metabolic disturbances and severe metabolic pathology.

Homocysteinemia: new information about an old risk factor for vascular disease.

OBJECTIVE: To determine the importance of homocysteinemia as a risk factor for atherosclerotic vascular disease. DESIGN: Literature review of published studies homocysteine as risk factor for atherosclerotic vascular disease. METHODS: MEDLINE search from 1969 to 1998 using homocysteine and vascular disease as search terms, from which 13 articles were selected for review. RESULTS: Homocysteine is a sulfur containing amino acid derivative formed during methionine metabolism. Inherited deficiencies of cystathionine B synthase or MTHF reductase result in markedly elevated plasma homocysteine levels and homocystinuria. Although rare, hereditary homocystinuria results in a variety of life threatening vascular complications occurring at a young age. Lesser degrees of homocysteinemia may result from vitamin B12, folate and pyridoxine deficiencies as well as a recently described mutation of the MTHF reductase gene. Homocysteinemia from these causes has been shown to increase the risk of coronary artery disease, peripheral artery disease, stroke, and venous thrombosis. Postulated mechanisms for this association are discussed. CONCLUSION: Homocysteinemia is a risk factor for premature vascular disease. The strength of this association is similar to that due to hyperlipidemia and tobacco use. Although vitamin supplementation with folic acid, B12, and B6 is able to reduce homocysteine levels in many persons, proof of the effectiveness of vitamin treatment in preventing or halting the progression of vascular disease is not yet available.

[A decision tree for abnormalities of plasma and urine lysine level]. / 'Un arbre de décision pour les anomalies de concentration de la lysine plasmatique et urinaire.

Variations of plasma lysine were divided in four situations: decreased, slightly decreased to normal, normal to slightly increased and always very increased. From each of these situations, and with the concentrations of urinary lysine; a flow chart is proposed for aminoacidopathies and organic acidurias in which lysine metabolism is primarily or secondarily disturbed.