The multifunctionality of FGF-2 in the adrenal medulla

 Chromaffin cells of the adrenal medulla and their tumor counterparts, the pheochromocytoma (PC12) cells, are well-established model systems in neurobiology. The development of sympathoadrenal progenitor cells to chromaffin cells can be studied with regard to developmental signals which trigger the differentiation. With regard to potential treatments of neurological disorders like Parkinson’s disease chromaffin cell grafting can be used as one therapeutical approach. The beneficial effect of chromaffin cell grafts is possibly not only related to the release of dopamine but may also be linked to the release of growth factors. One of the growth factors that is synthesized by chromaffin and PC12 cells is basic fibroblast growth factor (FGF-2). The experimental data available so far, are in agreement with different functional roles of FGF-2. This article summarizes the putative physiological functions of FGF-2 in the adrenal medulla. Three differential functional roles of FGF-2 are discussed: (1) as a differentiation factor for sympathoadrenal progenitor cells; (2) as a target-derived neurotrophic factor for preganglionic sympathetic neurons which innervate adrenal medullary cells; (3) as an auto-/paracrine factor in the adrenal medulla. Accepted: 21 August 1996     

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta?=??0.0264, p value?=?3.5?×?10^–8) in the discovery panel and was replicated in replication panel (beta?=??0.07, p value?=?0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value?=?1.4?×?10^–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

     

Impact of COVID-19 pandemic lockdown on myocardial infarction care

European Journal of Epidemiology - The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors...     

Serum cobalt and serum chromium level in 2 patients with chronic renal failure after total hip prosthesis implantation with metal-metal gliding contact

PURPOSE: The influence of chronic renal failure on serum cobalt and serum chromium in two patients with metal-on-metal bearing (Metasul) and cementless total hip arthroplasty (Alloclassic) is investigated. METHODS: Serum cobalt and serum chronium levels were determined in the postoperative course using atomic absorption spectrometry. RESULTS: Maximum values are found to be more than 100-fold elevated when compared to the reported median serum cobalt concentrations in patients with the same prosthesis type and no known renal disease. CONCLUSION: Chronic renal failure seems to be responsible for the marked elevation of serum cobalt and serum chromium. CLINICAL RELEVANCE: Despite evidence of adverse health reactions, a possible effect of long-term cobalt and chromium loading cannot be neglected. In our opinion, metal-on-metal bearings in THA should not be inserted in patients with chronic renal failure. Follow-up investigations (serum cobalt, serum chromium, serum creatinine, BUN, echocardiography) should be performed at short intervals.     

Prognostic value of apolipoprotein B and A-I in the prediction of myocardial infarction in middle-aged men and women: results from the MONICA/KORA Augsburg cohort study.

AIMS: To investigate the association between apolipoprotein B (apoB), A-I (apoA-I), the apoB/apoA-I ratio, and the incidence of coronary events. METHODS AND RESULTS: Analysis included 1414 men and 1436 women aged 35-64 years without a prior coronary event who participated in the population-based MONICA Augsburg survey 1984-85 (median followed-up period 13 years). Incidence of fatal and non-fatal myocardial infarction, and sudden cardiac death was assessed using data of the MONICA/KORA Augsburg coronary event registry. During follow-up, 114 incident coronary events occurred in men and 31 in women. In multivariable analysis, an increase of 1 standard deviation in the serum concentration of apoB was associated with an increased risk of coronary events in men [hazard ratio (HR)=1.49; 95% confidence interval (CI); 1.25-1.78] and in women (HR=1.73; 95% CI; 1.32-2.27). By contrast, elevated concentrations of apoA-I were not associated with a significantly decreased risk of coronary events in either sex (HR=0.91). Furthermore, the predictive power of the apoB/apoA-I ratio was similar to that of the total cholesterol/HDL cholesterol ratio in men and women. CONCLUSION: ApoB and the apoB/apoA-I ratio were strong predictors of coronary events in middle-aged men and women, whereas apoA-I did not add significantly to the estimation of future coronary risk.     

High prevalence of undiagnosed diabetes mellitus in Southern Germany: Target populations for efficient screening. The KORA survey 2000

AIMS/HYPOTHESIS: To estimate the prevalence of undiagnosed diabetes mellitus, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), and their relations with cardiovascular risk factors in the general population aged 55 to 74 years in Southern Germany. METHODS: Oral glucose tolerance tests were carried out in a random sample of 1353 subjects aged 55 to 74 years participating in the KORA (Cooperative Health Research in the Region of Augsburg) Survey 2000. Prevalences of glucose tolerance categories (1999 WHO criteria) were adjusted for sample probabilities. The numbers needed to screen (NNTS) to identify one person with undiagnosed diabetes were estimated from age-adjusted logistic regression models. RESULTS: Sample design-based prevalences of known and unknown diabetes, IGT, and IFG were 9.0%, 9.7%, 16.8%, 9.8% in men, and 7.9%, 6.9%, 16.0%, 4.5% in women, respectively. In both sexes, participants with undiagnosed diabetes had higher BMI, waist circumference, systolic blood pressure, triglycerides, uric acid, and lower HDL-cholesterol than normoglycaemic subjects. A combination of abdominal adiposity, hypertension, and parental diabetes in men resulted in a NNTS of 2.9 (95%CI: 2.0-4.6). In women, the combination of increased triglycerides, hypertension and parental diabetes history yielded a NNTS of 3.2 (95%CI: 2.2-5.1). CONCLUSION/INTERPRETATION: About 40% of the population aged 55 to 74 years in the Augsburg region have disturbed glucose tolerance or diabetes. Half of the total cases with diabetes are undiagnosed. Cardiovascular risk factors worsen among glucose tolerance categories, indicating the need for screening and prevention. Screening for undiagnosed diabetes could be most efficient in individuals with abdominal adiposity (men), hypertriglyceridaemia (women), hypertension, and parental diabetes history.     

Leisure time physical activity and the risk of type 2 diabetes in men and women from the general population

Aims/hypothesis The aim of this study was to examine sex-specific associations between leisure time physical activity and incident type 2 diabetes in a representative population sample in Germany.Methods The study was based on 4,069 men and 4,034 women (aged 25 to 74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995. Subjects were free of diabetes at baseline. Incident cases of type 2 diabetes were assessed in 1998 using a follow-up questionnaire. Sex-specific hazard ratios (HRs) were estimated from Cox proportional hazard models.Results A total of 145 cases of incident type 2 diabetes among men and 82 among women were registered during the mean follow-up period of 7.4 years. In both sexes, a high leisure time physical activity level was associated with a reduced risk of incident type 2 diabetes. After adjustment for confounding factors, the HR in highly active men (more than 2 h physical activity per week in summer and winter) was 0.83 (95% CI: 0.50–1.36). In contrast, highly active women had the lowest risk of type 2 diabetes even after multivariable adjustment (HR 0.24; 95% CI: 0.06–0.98). In subgroup analyses, after multivariable adjustment, the protective effect of moderate to high physical activity was significant in women with a BMI below 30 kg/m² (HR 0.24; 95% CI: 0.09–0.65) but not in women with a BMI of 30 kg/m² or higher (HR 0.97; 95% CI: 0.44–2.11).Conclusions/interpretation Leisure time physical activity is effective in preventing type 2 diabetes, especially in nonobese women, in the general population.     

Observational Study Mortality in Treated Primary Aldosteronism: The German Conn's Registry

In comparison with essential hypertension, primary aldosteronism (PA) is associated with an increased risk of cardiovascular morbidity. To date, no data on mortality have been published. We assessed mortality of patients treated for PA within the German Conn's registry and identified risk factors for adverse outcome in a case-control study. Patients with confirmed PA treated in 3 university centers in Germany since 1994 were included in the analysis. All of the patients were contacted in 2009 and 2010 to verify life status. Subjects from the population-based F3 survey of the Cooperative Health Research in the Region of Augsburg served as controls. Final analyses were based on 600 normotensive controls, 600 hypertensive controls, and 300 patients with PA. Kaplan-Meyer survival curves were calculated for both cohorts. Ten-year overall survival was 95% in normotensive controls, 90% in hypertensive controls, and 90% in patients with PA (P value not significant). In multivariate analysis, age (hazard ratio, 1.09 per year [95% CI, 1.03-1.14]), angina pectoris (hazard ratio, 3.6 [95% CI, 1.04-12.04]), and diabetes mellitus (hazard ratio, 2.55 [95% CI, 1.07-6.09]) were associated with an increase in all-cause mortality, whereas hypokalemia (hazard ratio, 0.41 per mmol/L [95% CI, 0.17-0.99]) was associated with reduced mortality. Cardiovascular mortality was the main cause of death in PA (50% versus 34% in hypertensive controls; P<0.05). These data indicate that cardiovascular mortality is increased in patients treated for PA, whereas all-cause mortality is not different from matched hypertensive controls.