RADseq data reveal a lack of admixture in a mouse lemur contact zone contrary to previous microsatellite results.

Microsatellites have been a workhorse of evolutionary genetic studies for decades and are still commonly in use for estimating signatures of genetic diversity at the population and species level across a multitude of taxa. Yet, the very high mutation rate of these loci is a double-edged sword, conferring great sensitivity at shallow levels of analysis (e.g. paternity analysis) but yielding considerable uncertainty for deeper evolutionary comparisons. For the present study, we used reduced representation genome-wide data (restriction site-associated DNA sequencing (RADseq)) to test for patterns of interspecific hybridization previously characterized using microsatellite data in a contact zone between two closely related mouse lemur species in Madagascar (Microcebus murinus and Microcebus griseorufus). We revisit this system by examining populations in, near, and far from the contact zone, including many of the same individuals that had previously been identified as hybrids with microsatellite data. Surprisingly, we find no evidence for admixed nuclear ancestry. Instead, re-analyses of microsatellite data and simulations suggest that previously inferred hybrids were false positives and that the program NewHybrids can be particularly sensitive to erroneously inferring hybrid ancestry. Combined with results from coalescent-based analyses and evidence for local syntopic co-occurrence, we conclude that the two mouse lemur species are in fact completely reproductively isolated, thus providing a new understanding of the evolutionary rate whereby reproductive isolation can be achieved in a primate.

Optimizing centrifugation of coagulation samples in laboratory automation.

BACKGROUND: High acceleration centrifugation conditions are used in laboratory automation systems to reduce the turnaround time (TAT) of clinical chemistry samples, but not of coagulation samples. This often requires separate sample flows. The CLSI guideline and manufacturers recommendations for coagulation assays aim at reducing platelet counts. For measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT) platelet counts (Plt) below 200×10(9)/L are recommended. Other coagulation assays may require even lower platelet counts, e.g., less than 10 × 10(9)/L. Unifying centrifugation conditions can facilitate the integration of coagulation samples in the overall workflow of a laboratory automation system. METHODS: We evaluated centrifugation conditions of coagulation samples by using high acceleration centrifugation conditions (5 min; 3280×g) in a single and two consecutive runs. RESULTS of coagulation assays [PT, APTT, coagulation factor VIII (F. VIII) and protein S] and platelet counts were compared after the first and second centrifugation. RESULTS: Platelet counts below 200×10(9)/L were obtained in all samples after the first centrifugation and less than 10 × 10(9)/L was obtained in 73% of the samples after a second centrifugation. Passing-Bablok regression analyses showed an equal performance of PT, APTT and F. VIII after first and second centrifugation whereas protein S measurements require a second centrifugation. CONCLUSIONS: Coagulation samples can be integrated into the workflow of a laboratory automation system using high acceleration centrifugation. A single centrifugation was sufficient for PT, APTT and F. VIII whereas two successive centrifugations appear to be sufficient for protein S activity.

Antibodies against potassium channel interacting protein 2 induce necrosis in isolated rat cardiomyocytes.

Auto-antibodies against cardiac proteins have been described in patients with dilated cardiomyopathy. Antibodies against the C-terminal part of KChIP2 (anti-KChIP2 [C-12]) enhance cell death of rat cardiomyocytes. The underlying mechanisms are not fully understood. Therefore, we wanted to explore the mechanisms responsible for anti-KChIP2-mediated cell death. Rat cardiomyocytes were treated with anti-KChIP2 (C-12). KChIP2 RNA and protein expressions, nuclear NF-κB, mitochondrial membrane potential Δψm, caspase-3 and -9 activities, necrotic and apoptotic cells, total Ca(2+) and K(+) concentrations, and the effects on L-type Ca(2+) channels were quantified. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB. Anti-KChIP2 (C-12)-treatment for 2 h significantly reduced KChIP2 mRNA and protein expression. Anti-KChIP2 (C-12) induced nuclear translocation of NF-κB after 1 h. After 6 h, Δψm and caspase-3 and -9 activities were not significantly changed. After 24 h, anti-KChIP2 (C-12)-treated cells were 75 ± 3% necrotic, 2 ± 1% apoptotic, and 13 ± 2% viable. Eighty-six ± 1% of experimental buffer-treated cells were viable. Anti-KChIP2 (C-12) induced significant increases in total Ca(2+) (plus 11 ± 2%) and K(+) (plus 18 ± 2%) concentrations after 5 min. Anti-KChIP2 (C-12) resulted in an increased Ca(2+) influx through L-type Ca(2+) channels. In conclusion, our results suggest that anti-KChIP2 (C-12) enhances cell death of rat cardiomyocytes probably due to necrosis.

Beta-trace protein in ascites and pleural effusions: limits of CSF leakage detection.

Rhino- and/or otoliquorrhea can be diagnosed by detecting beta-trace protein (ß-TP) in nasal or ear secretions, as ß-TP is found in high concentrations in cerebrospinal fluid (CSF) but not in serum. CSF fistulae following trauma or surgery can also occur at other anatomical sites, resulting in CSF leakage into the thoracic and abdominal cavities. By analogy, determination of ß-TP has also been used to diagnose CSF admixture in pleural effusions and ascites. However, no systematic study has yet evaluated the concentrations of ß-TP in such fluids in the absence of CSF. To determine the validity of ß-TP determination as a marker for the presence of CSF, we investigated ß-TP concentrations in pleural effusions and ascites without CSF admixture. Patients from whom samples of ascites or pleural effusion and a paired plasma sample were available were investigated. One hundred sixty-four patients were prospectively recruited. ß-TP concentrations were determined by nephelometry. Mass spectrometric proteome analysis confirmed the presence of ß-TP in the samples. Median ß-TP concentrations detected in ascites and pleural effusions (range, 0.014-26.5 mg/L, median 2.29 mg/L) exceeded the corresponding plasma concentrations 2.6-fold. According to cutoffs published to diagnose rhino- and otoliquorrhea, between 6.1% and 95.7% of the specimens would have been erroneously rated CSF-positive. Protein analysis confirmed the presence of ß-TP in pleural effusion and ascites. Ascites and pleural effusion contain high concentrations of ß-TP that exceed the levels in corresponding plasma. Therefore, ß-TP is not a specific marker for the presence of CSF in these fluids.

Are serum TSH levels associated with oxidized low-density lipoprotein? Results from the Study of Health in Pomerania.

OBJECTIVE: Oxidized LDL (oxLDL) is involved in the pathogenesis of atherosclerosis. Thus, it is important to investigate putative risk factors for increased oxLDL. Evidence suggests that, compared to euthyroid individuals, LDL-cholesterol (LDL-C) levels are lower in individuals with overt hyperthyroidism. Whereas oxidization of LDL-C into oxLDL is increased in overt hyper- and hypothyroidism, it has not been investigated whether subclinical thyroid dysfunction impacts on oxLDL levels in general. We have analysed the association between serum thyrotrophin (TSH) levels and oxLDL in a population-based study. DESIGN, PATIENTS AND MEASUREMENTS: Of the 4308 individuals enrolled in the Study of Health in Pomerania, data from 3519 individuals were analysed (680 missing the oxLDL variable). oxLDL was measured by the oxLDL competitive ELISA on a BEP 2000. Multivariable linear regression models were performed to assess the association between serum TSH and oxLDL levels. RESULTS: TSH was positively associated with oxLDL in a curvilinear fashion with increasing serum TSH levels. Subgroup analyses revealed a significant association only in the group of individuals >60 years. Additionally, serum TSH levels were not associated with the ratio of oxLDL to LDL (ß = -0·04; 95% CI = -0·08, 0·01; P = 0·084). CONCLUSIONS: We demonstrate an association between serum TSH and oxLDL levels especially in the range of subclinical thyroid disease. Our study suggests that serum TSH levels affect LDL-C production or clearance rather than the LDL-C oxidation processes.

Association of plasma aldosterone with the metabolic syndrome in two German populations.

OBJECTIVE: The aim of this study was to analyze the potential association of the plasma aldosterone concentration (PAC) with the metabolic syndrome (MetS) and its components in two German population-based studies. METHODS: We selected 2830 and 2901 participants (31-80 years) from the follow-ups of the Study of Health in Pomerania (SHIP)-1 and the Cooperative Health Research in the Region of Augsburg (KORA) F4 respectively. MetS was defined as the presence of at least three out of the following five criteria: waist circumference ≥94 cm (men (m)) and ≥80 cm (women (w)); high-density lipoprotein (HDL) cholesterol <1.0 mmol/l (m) and <1.3 mmol/l (w); blood pressure ≥130/85 mmHg or antihypertensive treatment; non-fasting glucose (SHIP-1) ≥8 mmol/l, fasting glucose (KORA F4) ≥5.55 mmol/l or antidiabetic treatment; non-fasting triglycerides (SHIP-1) ≥2.3 mmol/l, fasting triglycerides (KORA F4) ≥1.7 mmol/l, or lipid-lowering treatment. We calculated logistic regression models by comparing the highest study- and sex-specific PAC quintiles versus all lower quintiles. RESULTS: MetS was common with 48.1% (m) and 34.8% (w) in SHIP-1 and 42.7% (m) and 27.5% (w) in KORA F4. Our logistic regression models revealed associations of PAC with MetS, elevated triglycerides, and decreased HDL cholesterol in SHIP-1 and KORA F4. CONCLUSIONS: Our findings add to the increasing evidence supporting a relation between aldosterone and MetS and suggest that aldosterone may be involved in the pathophysiology of MetS and lipid metabolism disorders.

Common carotid intima-media thickness and framingham risk score predict incident carotid atherosclerotic plaque formation: longitudinal results from the study of health in Pomerania.

BACKGROUND AND PURPOSE: Cross-sectional studies describe a positive association between common carotid artery intima-media thickness (CCA-IMT) and carotid plaques (CP). However, longitudinal data on the predictive value of CCA-IMT for occurrence of CP are limited. Therefore, the role of increasing CCA-IMT in the atherosclerotic process is still discussed controversially. METHODS: We investigated the predictive value of CCA-IMT and the Framingham risk score (FRS) for incident CP formation in a population-based longitudinal study of 1922 subjects aged 45 to 81 years who underwent ultrasonography of both carotid arteries and received vascular risk factor assessment at baseline and after 5 years. CP was defined as any protruding focal thickening of the intima-media complex. Incident CP formation during follow-up was defined as the appearance of at least 1 CP in a previously plaque-free arterial segment (right and left common, internal, and external carotid arteries and carotid bifurcation). RESULTS: Among the 636 subjects without CP at baseline, 418 (66%) had at least 1 incident CP during follow-up. In a multivariable negative binominal regression model adjusted for age, gender, and the FRS, the number of arterial segments affected by incident CP was 1.53-fold higher (CI, 1.12-2.07; P<0.01) for subjects in the highest quartile of the overall CCA-IMT distribution compared to those in the lowest quartile. CONCLUSIONS: Both CCA-IMT and FRS independently predict incident CP formation. The risk of CP formation may actually be underestimated in subjects with low FRS and high IMT.

A descriptive analysis of relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke.

BACKGROUND: The aims of the present study were to examine relations between parents' self-reported smoking behavior and infants' daily exposure to environmental tobacco smoke, as assessed by urinary cotinine-to-creatinine ratio (CCR), and to describe the CCR over seven days among infants at home. METHODS: A convenience sample of 27 households was drawn. Each household had to have at least one daily tobacco smoker and one child up to three years of age. Over a seven-day period, urine samples were obtained from the child daily. To examine relations between parents' self-reported smoking and infants' daily CCR, generalized estimating equation (GEE) analysis was used. RESULTS: The data revealed that infants from households with indoor smoking had higher CCRs than infants in households with outdoor smoking. CCRs were higher in girls than in boys. Older infants had lower CCRs than younger infants. Smoking outside the home versus inside the home, infant's gender, and infants' age accounted for 68% of the variance in CCR in a GEE data analysis model. No increase or decrease of CCR over time was found. CONCLUSION: The findings suggest that parents' self-reported smoking indoors at home versus outdoors is predictive of CCR among infants three and younger. Higher CCR concentrations in girls' urine need further examination. Furthermore, significant fluctuations in daily CCR were not apparent in infants over a seven-day time period.

Reference intervals for eight measurands of the blood count in a large population based study.

BACKGROUND: The blood count is widely used in clinical practice. Well defined reference intervals for each measurand are essential for correct clinical interpretation of results. Most previous studies have not been population-based. We therefore calculated reference intervals for several hematological measurands from a sample of the general adult population of Northeastern Germany. METHODS AND RESULTS: We used data from 2967 healthy individuals recruited for the population-based Study of Health in Pomerania (SHIP). Reference intervals were calculated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) using the bootstrap method for the age range from 20 to 79 years and, in addition, stratified according to age and gender with both bootstrap and quantile regression procedures. Reference ranges for erythrocytes, hemoglobin and hematocrit increased with age in women but decreased in men. CONCLUSIONS: Our reference intervals were lower than those previously published for erythrocytes, hemoglobin, hematocrit and leukocytes but higher for Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH). Different laboratory methods and study populations may lead to disparity in results.

Regional differences in the prevalence of left ventricular hypertrophy within Germany.

BACKGROUND: There are considerable regional disparities in the prevalence of cardiovascular risk factors within Germany. We undertook this study to investigate differences in the prevalence of left ventricular hypertrophy (LVH) between northeast and southwest Germany. METHODS: Data from two population-based studies, Kooperative Gesundheitsforschung im Raum Augsburg (KORA) conducted in southwest and Study of Health in Pomerania (SHIP) conducted in northeast Germany, were utilized. The study population comprised 2,516 women and men (835 from KORA and 1,681 from SHIP) aged 45-74 years who had no history of myocardial infarction. Echocardiograms were obtained according to standard protocols. Left ventricular mass (LVM), left ventricular mass indexed for body height, and left ventricular hypertrophy were used as dependent variables in multivariable analyses. RESULTS: SHIP participants had higher LVM and left ventricular mass index values compared with KORA participants. These differences remained after analyses were adjusted for major confounders including obesity and hypertension. Consequently, there were higher proportions of LVH in SHIP compared with KORA across all 10-year age groups. Multivariable logistic regression revealed that the odds for LVH in participants living in northeast Germany were higher in women and men, respectively, by 1.57 (95% confidence interval: 1.18-2.09) and 1.68 (95% confidence interval: 1.25-2.27) than in participants living in southwest Germany. Potential methodological differences between studies do not seem to account for these findings. CONCLUSION: There is a higher prevalence of LVH in northeast compared with southwest Germany. Regional disparities in hypertension and overweight only partly explain this difference.

Mortality and serum insulin-like growth factor (IGF)-I and IGF binding protein 3 concentrations.

BACKGROUND: Previous studies provided conflicting results regarding the association of serum IGF-I or IGF-binding protein-3 (IGFBP-3) and mortality. The aim of this study was to assess the relation of IGF-I and IGFBP-3 levels with mortality from all causes, cardiovascular disease (CVD), and cancer in a prospective population-based study. METHODS: From the Study of Health in Pomerania (SHIP) 1988 men and 2069 women aged 20-79 yr were followed up on average 8.5 yr. Causes of deaths were coded according to the International Classification of Diseases, 10th revision. Serum IGF-I and IGFBP-3 levels were determined by chemiluminescence immunoassays and categorized into three groups (low, normal, high) according to the sex- and age-specific 10th and 90th percentiles. RESULTS: Adjusted analyses revealed that men with low but not high IGF-I levels had an almost 2-fold higher risk of all-cause mortality [hazard ratio (HR) 1.92 (95% confidence interval [CI] 1.35; 2.73)], CVD mortality [HR 1.92 (95% CI 1.00; 3.71)], and cancer mortality [HR 1.85 (95% CI 1.00; 3.45)] compared with men with normal IGF-I levels. In women, no association between IGF-I and mortality was found. Moreover, low IGFBP-3 levels were associated with higher all-cause mortality in men [HR 1.87 (95% CI 1.31; 2.64)] and women [HR 1.63 (95% CI 0.96; 2.76)]. CONCLUSIONS: The present study found inverse associations between IGF-I or IGFBP-3 levels and mortality from all causes, CVD, or cancer in men and between IGFBP-3 and all-cause mortality in women.

Prevalence and determinants of increased serum lipase levels in a general population.

OBJECTIVES: There is little information on the prevalence of increased serum lipase levels and its determinants from population-based studies. The present study was performed to provide such information. METHODS: We used data from the 4275 subjects aged 20 to 79 years who were recruited for the population-based Study of Health in Pomerania. Serum lipase levels were determined colorimetrically; levels > or =3.17 micromol/s x l were considered increased. RESULTS: The prevalence of increased serum lipase levels was 3.4%. The prevalence of self-reported chronic pancreatitis in this population was 0.7%. Subjects with and without increased serum lipase levels did not differ with respect to symptoms indicative of pancreatitis including abdominal feeling of fullness, abdominal pain, nausea, and loss of weight. High serum lipase levels correlated with advanced age, increased serum creatinine levels, and use of steroids or enalapril. CONCLUSIONS: Increased serum lipase levels are unrelated to pancreatitis-related symptoms. Renal insufficiency and prevalent pancreatitis explain increased serum lipase levels in a minority of subjects. In clinical practice, drugs including steroids and enalapril should be excluded as cause of increased serum lipase levels. The predictive roleof lipase measurements with respect to other pancreatic or extrapancreatic disorders has to be investigated in cohort studies.

No association of seropositivity for anti-Borrelia IgG antibody with mental and physical complaints.

Undiagnosed chronic Lyme disease caused by Borrelia burgdorferi is considered a differential diagnoses in medically unexplained symptoms like arthralgias, distal paresthesias, depressive symptoms, lack of concentration and fatigue. The aims of the study were to assess the association of mental and physical complaints with seropositivity for anti-Borrelia IgG in a general population sample. Seropositivity indicated an infection with Borrelia in the past. The Study of Health in Pomerania was conducted in a community living in a region with endemic Lyme disease. Mental and physical complaints were assessed on 38 items with the von Zerssen's complaint scale. IgG antibodies to Borrelia were determined by ELISA in 4264 individuals. Seropositivity was analyzed applying two cut-off scores (>5 and >10 IU/ml). IgG antibodies to Borrelia were found positive in 388 subjects (9.1%) applying the >5 IU/ml cut-off and in 130 subjects (3.0%) applying the >10 IU/ml cut-off. In multivariate analyses (MANCOVA), both definitions of seropositivity were not associated with increased mental or physical complaints while adjusting for gender, age, employment status, rural residency, physical activity, diabetes mellitus and number of chronic diseases. In the general population, seropositivity for anti-Borrelia IgG antibodies was not associated with an increase of self-rated mental or physical complaints or impairments. Therefore, clinicians should not overvalue seropositivity for anti-Borrelia IgG as a medical cause for unexplained mental or physical complaints.

Inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus.

AIM: In a general adult population, we have demonstrated an inverse association between periodontitis and respiratory allergies that is in line with the hygiene hypothesis suggesting a protective effect of infections against the development of allergies. The objective of the present study was to investigate the association between periodontitis and respiratory allergies in a type 1 diabetes mellitus population. MATERIAL AND METHODS: The study population comprised 170 patients with type 1 diabetes mellitus aged 17-80 years. Respiratory allergies were present in 22 subjects. The attachment loss (AL) was measured. Periodontitis was defined according to the percentage of surfaces that exceeded 3 mm AL (healthy, mild, moderate, severe periodontal conditions). RESULTS: Our adjusted analyses revealed an inverse association between periodontitis and respiratory allergies. For increasing AL, a trend towards a decreasing risk was present for respiratory allergies (p(trend)<0.05). Compared with subjects with healthy periodontal conditions, individuals with severe periodontal conditions had the lowest risk of respiratory allergies [odds ratios (OR) 0.06 (95% confidence interval (CI) 0.01-0.39)], followed by subjects with moderate AL [OR 0.14 (95% CI 0.03-0.63)] and mild AL [OR 0.32 (95% CI 0.09-1.08)]. CONCLUSION: There is a strong inverse association between periodontitis and respiratory allergies in patients with type 1 diabetes mellitus. These findings further support the hygiene hypothesis.

Dose-dependent titration of prorenin and blood pressure in Cyp1a1ren-2 transgenic rats: absence of prorenin-induced glomerulosclerosis.

OBJECTIVE: Prorenin has been associated with cardiovascular disease and the development of glomerulosclerosis via a renin/prorenin receptor. In cyp1a1ren-2 transgenic rats, prorenin levels and arterial pressure can be increased by oral administration of indole-3-carbinol (I3C). The transgenic strain has been used as a model of malignant hypertension. METHODS: The present study was designed to test the hypotheses that (i) low doses of I3C would result in dose-dependent sustained increases in arterial pressure without signs of malignancy, making cyp1a1ren-2 transgenic rats a useful model to study nonmalignant hypertension, and (ii) cyp1a1ren-2 transgenic rats would develop glomerulosclerosis when they were chronically exposed to 0.125% I3C in their diet. RESULTS: I3C treatment for 2 weeks resulted in increases of plasma prorenin concentrations and arterial pressure in a dose-dependent manner. Rats thrived well over a period of 12 weeks on dietary I3C concentrations (wt/wt) of 0.125%. Plasma prorenin concentration rose from 0.1 +/- 0.1 microg to 17.9 +/- 5.0 mug angiotensin I/ml per h (P < 0.01) and mean arterial pressure increased to a plateau of 170 +/- 5 mmHg (P < 0.001) between weeks 6 and 12. After 12 weeks of 0.125% I3C, rats exhibited moderate hypertensive renal vasculopathy, but no histological signs of glomerulosclerosis. CONCLUSIONS: The cyp1a1ren-2 transgenic rat model allows for chronic dose-dependent titration of arterial pressure by a simple and non-invasive intervention, making this strain a useful model to study malignant and nonmalignant arterial hypertension. High circulating prorenin levels per se do not cause glomerulosclerosis.

Reference ranges of serum IGF-1 and IGFBP-3 levels in a general adult population: results of the Study of Health in Pomerania (SHIP).

OBJECTIVE: Insulin-like growth factor I (IGF-1), which is mostly carried by IGF binding protein 3 (IGFBP-3), mediates endocrine actions of growth hormone and represents an important prognostic factor for systemic diseases. The main objectives of the present study were (1) to calculate age- and sex-specific reference values for serum IGF-1 and IGFBP-3 levels using the Gaussian mean+/-1.96 *standard deviation method and the quantile regression method and (2) to perform a comparison of the results from both statistical methods. DESIGN: Cross-sectional study (Study of Health in Pomerania). The study population included 2499 men and women aged 20-79 years. METHODS: Serum IGF-1 and IGFBP-3 levels were determined by chemiluminescence immunoassays. Linear and quantile regressions were performed to calculate age- and sex-related reference ranges. RESULTS: Both statistical methods generated different results: The reference ranges based on linear regression identified 43 (1.7%) subjects with serum IGF-1 levels and 99 (4.0%) subjects with serum IGFBP-3 levels outside the reference range. Using quantile regression, 117 (4.7%) or 118 subjects (4.7%) with serum IGF-1 or IGFBP-3 levels outside the range were detected, respectively. CONCLUSION: The present study established age- and sex-specific reference ranges for serum IGF-1 and IGFBP-3 levels. Quantile regression should be preferred to calculate reference ranges because a better concordance to original data is possible due to no distribution assumption are required and the robustness against outliers is given.

Association between serum insulin-like growth factor-I levels and thyroid disorders in a population-based study.

OBJECTIVE: There is current debate on whether serum IGF-I levels are associated with thyroid disorders. The aims of the present study were: 1) to investigate possible associations between serum IGF-I levels and thyroid disorders and 2) to analyze the role of serum IGF binding protein (IGFBP)-3 and TSH levels for these associations. DESIGN: This was a cross-sectional Study of Health in Pomerania. SETTING: The study was conducted in the general population of northeast Germany. SUBJECTS: The study population comprised 3662 subjects (1746 women) without history of thyroid disorders. INTERVENTIONS: No interventions have been performed. MAIN OUTCOME MEASURES: Goiter and thyroid nodules were determined by ultrasound. Serum TSH levels less than 0.25 mIU/liter were considered decreased. RESULTS: Adjusted for major confounders and risk factors for thyroid disorders, subjects with serum IGF-I levels above the upper tertile had higher odds for goiter relative to subjects with serum IGF-I levels below the lower tertile [odds ratio (OR) 1.67; 95% confidence interval (CI) 1.24-2.26 in women; OR 2.04; 95% CI 1.55-2.68 in men]. A similar association was present for thyroid nodules in men (OR 1.64; 95% CI 1.17-2.32) and for decreased serum TSH levels in women (OR 1.65; 95% CI 1.00-2.69). Serum IGFBP-3 levels were not associated with thyroid disorders and did not represent effect modifiers for the association between serum IGF-I levels and the endpoints. CONCLUSIONS: We conclude that high serum IGF-I levels are associated with goiter. Whereas high serum IGF-I levels are also related to thyroid nodules in men, they are related to decreased serum TSH levels in women. Serum IGFBP-3 and TSH levels did not modulate these associations.

Impaired coronary function in Wistar Ottawa Karlsburg W rats-a new model of the metabolic syndrome.

The metabolic syndrome is associated with an increased risk for coronary heart disease. The underlying mechanisms are not well understood. The present study was designed to investigate coronary function in Wistar Ottawa Karlsburg W (WOKW) rats, a new animal model of the metabolic syndrome. The responses of coronary artery segments from WOKW and Dark Agouti (DA) control rats of different ages to several physiological vasoconstrictors and vasodilators were measured in a small vessel wire myograph, and potential mechanisms involved in the differential responses between the two strains were investigated. WOKW showed increased alpha(1)-adrenoceptor-mediated coronary constriction at 3 and 10 months of age, as well as seriously blunted beta-adrenoceptor-mediated coronary relaxation at 16 months of age. Responses to non-adrenergic agonists were not altered in WOKW compared to DA. The alpha(1)-adrenoceptor-mediated coronary constriction in WOKW was completely blocked by rho-kinase inhibition. Induced hyperinsulinemia did not cause increased alpha(1)-adrenoceptor-mediated coronary constriction or impaired beta-adrenoceptor-mediated coronary relaxation in DA. The association between blunted coronary beta-adrenoceptor responsiveness and the metabolic syndrome was confirmed in Zucker diabetic fatty rats. We conclude that the metabolic syndrome in WOKW rats is associated with impaired coronary function due to altered adrenoceptor sensitivity. The latter may contribute to inappropriately elevated coronary tone in insulin-resistant subjects, especially when sympathetic activity to the heart is increased.