CT mapping of the vertebral level of right adrenal vein

PURPOSEWe aimed to evaluate the accuracy of multidetector computed tomography (MDCT) venous mapping for the localization of the right adrenal veins (RAV) in patients suffering from primary aldosteronism.METHODSMDCT scans of 75 patients with primary aldosteronism between March 2008 and November 2011 were evaluated by two readers (a junior [R1] and a senior [R2] radiologist) according to the following criteria: quality of RAV depiction (scale, 1–5), localization of the RAV confluence with regard to the inferior vena cava, and depiction of anatomical variants. Results were compared with RAV venograms obtained during adrenal vein sampling and corroborated by laboratory testing of cortisol in selective RAV blood samples. Kappa statistics were calculated for interobserver agreement and for concordance of MDCT mapping with the gold standard.RESULTSSuccessful RAV sampling was achieved in 69 of 75 patients (92%). Using MDCT mapping, adrenal veins could be visualized in 78% (R1, 54/69) and 77% (R2, 53/69) of patients. MDCT mapping led to correct identification of RAV in 70% (R1, 48/69) and 88% (R2, 61/69) of patients. Venograms revealed five cases of anatomical variants, which were correctly identified in 60% (R1, R2). MDCT-based localizations were false or misleading in 16% (R1, 11/69) and 7% (R2, 5/69) of cases.CONCLUSIONPreinterventional MDCT mapping may facilitate successful catheterization in adrenal vein sampling

Voting for Direct Democracy: Evidence from a Unique Popular Initiative in Bavaria

We analyze a constitutional change in the German State of Bavaria where citizens, not politicians, granted themselves more say in politics at the local level through a constitutional initiative at the state level. This institutional setting allows us to focus on revealed preferences for direct democracy and to identify factors which explain this preference. Empirical results suggests support for direct democracy is rather related to dissatisfaction with representative democracy in general than with an elected governing party

Consumption of pasteurized human lysozyme transgenic goats’ milk alters serum metabolite profile in young pigs

Nutrition, bacterial composition of the gastrointestinal tract, and general health status can all influence the metabolic profile of an organism. We previously demonstrated that feeding pasteurized transgenic goats’ milk expressing human lysozyme (hLZ) can positively impact intestinal morphology and modulate intestinal microbiota composition in young pigs. The objective of this study was to further examine the effect of consuming hLZ-containing milk on young pigs by profiling serum metabolites. Pigs were placed into two groups and fed a diet of solid food and either control (non-transgenic) goats’ milk or milk from hLZ-transgenic goats for 6 weeks. Serum samples were collected at the end of the feeding period and global metabolite profiling was performed. For a total of 225 metabolites (160 known, 65 unknown) semi-quantitative data was obtained. Levels of 18 known and 4 unknown metabolites differed significantly between the two groups with the direction of change in 13 of the 18 known metabolites being almost entirely congruent with improved health status, particularly in terms of the gastrointestinal tract health and immune response, with the effects of the other five being neutral or unknown. These results further support our hypothesis that consumption of hLZ-containing milk is beneficial to health

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Understanding how we age: insights into inflammaging

Inflammaging is characterized by the upregulation of the inflammatory response that occurs with advancing age; its roots are strongly embedded in evolutionary theory. Inflammaging is believed to be a consequence of a remodelling of the innate and acquired immune system, resulting in chronic inflammatory cytokine production. Complex interrelated genetic, environmental and age-related factors determine an individual’s vulnerability or resilience to inflammaging. These factors include polymorphisms to the promoter regions of cytokines, cytokine receptors and antagonists, age-related decreases in autophagy and increased adiposity. Anti-inflammaging describes the upregulation of the hypothalamic-pituitary axis in response to inflammaging, leading to higher levels of cortisol, which in turn may be detrimental, contributing to less successful ageing and frailty. This may be countered by the adrenal steroid dehydroepiandrosterone, which itself declines with age, leaving certain individuals more vulnerable. Inflammaging and anti-inflammaging have both been linked with a number of age-related outcomes, including chronic morbidity, functional decline and mortality. This important area of research offers unique insights into the ageing process and the potential for screening and targeted interventions

Aldosterone excess impairs first phase insulin secretion in primary aldosteronism.

Context: Primary aldosteronism (PA) represents the most frequent cause of secondary arterial hypertension. Conflicting data have been published regarding the effect of aldosterone excess on glucose metabolism. Objective: Our aim was to analyze insulin sensitivity and beta-cell function in a cohort of PA patients. Prospective follow-up investigations were performed in a subgroup of patients before and after adrenalectomy to assess the metabolic outcome. Design: Oral glucose tolerance test, combined intravenous glucose tolerance test, hyperinsulinemic-euglycemic glucose clamp test, and arginine test were carried out after a 12-hour fasting period. Patients: Twenty-two consecutive patients with both unilateral aldosterone-producing adenoma and bilateral idiopathic adrenal hyperplasia were recruited through the Munich center of the German Conn's Registry. The control group of patients with essential hypertension (n = 11) of corresponding age and body mass index was recruited from our hypertension unit. Anormotensive cohort (n = 11) served as a further control group. Results: At baseline, first-phase insulin reaction in intravenous glucose tolerance test was significantly reduced in patients with PA as compared to normal controls(36.0 [24.0; 58.7] vs 90.1 [52.6; 143.8] mu U/mL, P = .031) and lower in comparison to essential hypertension without reaching statistical significance (53.2 [30.8; 73.3] mu U/mL, P = .123). The study was repeated 6 months after unilateral adrenalectomy in 9 consecutive patients with aldosterone-producing adenoma. At this time point, blood pressure had been normalized in most of the patients while body mass index remained unchanged (26.9 [25.5; 37.6] vs 27.5 [25.1; 35.6] kg/m(2), P = .401). First-phase insulin reaction in response to glucose significantly increased at follow-up (from 36.0 [25.5; 58.7] to 48.5 [40.4; 95.2] mu U/mL, P = .038, n = 9). In contrast, insulin sensitivity and response to iv arginine did not differ before and after adrenalectomy. Conclusion: Aldosterone excess has a direct negative effect on beta-cell function in patients with PA. After adrenalectomy, glucose-induced first-phase insulin secretion improves significantly in the patients

Volumetric and densitometric evaluation of the adrenal glands in patients with primary aldosteronism

OBJECTIVE To evaluate volumetric and densitometric properties of the adrenal glands in patients with unilateral and bilateral disease in comparison with normal controls. DESIGN A total of 77 patients (56 males and 21 females) diagnosed with primary aldosteronism (PA) with a mean age of 53 ± 10 years were prospectively enrolled. Unenhanced and contrast-enhanced computed tomography scans were analysed for adrenal volumes and mean densities. These values were compared with normal controls and between PA subtypes. RESULTS Adrenals containing an aldosterone-producing adenoma (APA, n = 56) had on average higher attenuation values as compared to adrenals with bilateral adrenal hyperplasia (n = 21). Mean adrenal gland volume in PA patients was not significantly different between PA subtypes. In comparison with normal adrenal glands, volumes were significantly higher in PA patients (P < 0·0001) including adrenals contralateral to APAs, which were significantly larger in comparison with controls. CONCLUSION Independent of subtype differentiation, adrenal volumetry reveals higher adrenal volumes in PA patients in comparison with normal controls. These findings provide indirect evidence for a general adrenal growth dysregulation in the context of PA