Zinc ions in beta-cells of obese, insulin-resistant, and type 2 diabetic rats traced by autometallography

Zinc ions in the secretory granules of beta-cells are known to glue insulin molecules, creating osmotically stable hexamers. When the secretory granules open to the surface, the zinc ion pressure decreases rapidly and pH levels change from acid to physiological, which results in free insulin monomers and zinc ions. The released zinc ions have been suggested to be involved in a paracrine regulation of alpha- and beta-cells. Since zinc is intimately involved in insulin metabolism and because zinc homeostasis is known to be disturbed in type 2 diabetes, we decided to study the ultrastructural localisation of zinc ions in insulin-resistant and type 2 diabetic rats as compared to controls. By means of autometallography, the only method available for demonstrating zinc ions at ultrastructural levels, we found zinc ions in the secretory granules and adjacent to the plasma membrane. The membrane-related staining outside the plasma membrane reflects release of zinc ions during exocytosis. No apparent difference was found in the ultrastructural localisation of zinc ions when we compared the obese Zucker (fa/fa) rats, representing the insulin resistance syndrome, and the GK rats, representing type 2 diabetes, with controls. This suggests that the ultrastructural localisation of zinc ions is unaffected by the development of type 2 diabetes in rats in a steady state of glycaemia.     

Rekonvaleszentenserumbehandlung der Encephalitis und Frage Ihrer ätiologie

Zusammenfassung Auch die sporadischen Fälle von Economo-Encephalitis sollen — zur Unterscheidung von anderen sporadischen Encephalitiden — als Encephaliticaepidemica bezeichnet werden, weil dieser Begriff als Krankheitsbezeichnung allgemein eingeführt ist.Zwei frische Fälle (1930) typischer schwerer kindlicher Economo-Encephalitis wurden durch i.m. Injektion von R.S. der Göttinger Encephalitisstation prompt beeinflußt und vorläufig geheilt.Jeder frische Fall von epidemischer Encephalitis soll auch im Kindesalter alsbald mit R.S. behandelt werden.Die Ergebnisse der Hornhautimpfungen vonKnauer undJaensch bilden keinen hinreichenden Grund, etwa aus ätiologischen Gründen die nosologische Krankheitseinheit Encephalitica epidemica in ihrer bisherigen Form aufzugeben.Klinischer Verlauf und Obduktionsbefund zweier Fälle, die das Bild der abakteriellen eitrigen Meningitis darboten, werden mitgeteilt. Keine Beeinflussung durch das Göttinger R.S., Hornhautimpfung mit den Liquores (Prof.Grüter) negativ.Nach einem Vortrage, gehalten auf der Tagung Südwestdeutscher und Rheinischwestfälischer Kinderärzte in Gießen am 12. April 1931.     

Cost-effectiveness of preoperative localization studies in primary hyperparathyroid disease.

OBJECTIVE: To evaluate the effect of preoperative localization studies on the surgical management of patients with primary hyperparathyroid disease (PHPT). SUMMARY BACKGROUND DATA: Reported cure rates of initial surgical exploration for PHPT are close to 95%. Preoperative localization studies are frequently obtained to improve surgical success and decrease operative time. METHODS: Initial cervical exploration was performed in 113 patients with PHPT from 1981 to 1993. Twenty-four patients (21%) had surgery without preoperative localization studies. The remaining 89 patients (79%) had 132 noninvasive preoperative localization studies. Success of the localization studies in tumor localization, pathologic findings, postoperative serum calcium levels, and operative times were compared. Patient costs of the studies were calculated. RESULTS: Disease was identified during operation in 23 of 24 patients (96%) having cervical exploration without preoperative localization studies, and they had normal calcium levels after surgery. Eighty-seven of 89 patients (98%) having preoperative localization studies were surgically cured. The highest sensitivity rate (60%) and highest positive predictive value (79%) of the localization studies were found with thallium-technetium scintiscanning. Average cost of the localization studies was $901 per patient. Combination studies were obtained in 32 patients at an average cost of $1,314 per patient without improving sensitivity. Mean operating time did not differ for localized and nonlocalized patients. CONCLUSIONS: Preoperative localization studies did not improve parathyroid localization or cure rate and did not substantially shorten operating time in initial cervical exploration for PHPT. The economic burden of routine preoperative localization studies in these patients is not justified.     

Early Oestrogens in Shaping Reproductive Networks: Evidence for a Potential Organisational Role of Oestradiol in Female Brain Development

A central tenet of contemporary theories on mammalian brain and behavioural sexual differentiation is that an organisational action of testosterone, secreted by the male’s testes, controls male‐typical aspects of brain and behavioural development, whereas no active perinatal sex hormone signalling is required for female‐typical sexual differentiation. Furthermore, the available evidence suggests that many, although not all, of the perinatal organisational actions of testosterone on the development of the male brain result from the cellular effects of oestradiol formed via neural aromatisation of testosterone. However, a default developmental programme for the female brain has been criticised. Indeed, we review new results obtained in aromatase knockout mice indicating that oestradiol actively contributes to the differentiation of female‐typical aspects of brain and behavioural sexual differentiation. Furthermore, we propose that male‐typical neural and behavioural differentiation occurs prenatally in genetic males under the influence of oestradiol, which is avoided in foetal genetic females by the neuroprotective actions of α‐fetoprotein, whereas female‐typical neural and behavioural differentiation normally occurs postnatally in genetic females under the influence of oestradiol that is presumably produced by the ovaries.     

Turning back from the brink: Detecting an impending regime shift in time to avert it

Ecological regime shifts are large, abrupt, long-lasting changes in ecosystems that often have considerable impacts on human economies and societies. Avoiding unintentional regime shifts is widely regarded as desirable, but prediction of ecological regime shifts is notoriously difficult. Recent research indicates that changes in ecological time series (e.g., increased variability and autocorrelation) could potentially serve as early warning indicators of impending shifts. A critical question, however, is whether such indicators provide sufficient warning to adapt management to avert regime shifts. We examine this question using a fisheries model, with regime shifts driven by angling (amenable to rapid reduction) or shoreline development (only gradual restoration is possible). The model represents key features of a broad class of ecological regime shifts. We find that if drivers can only be manipulated gradually management action is needed substantially before a regime shift to avert it; if drivers can be rapidly altered aversive action may be delayed until a shift is underway. Large increases in the indicators only occur once a regime shift is initiated, often too late for management to avert a shift. To improve usefulness in averting regime shifts, we suggest that research focus on defining critical indicator levels rather than detecting change in the indicators. Ideally, critical indicator levels should be related to switches in ecosystem attractors; we present a new spectral density ratio indicator to this end. Averting ecological regime shifts is also dependent on developing policy processes that enable society to respond more rapidly to information about impending regime shifts.