A pilot study of Connexin 43 (Cx43) in human bladder tissue in patients with idiopathic detrusor overactivity

OBJECTIVE: Aim of the study was to compare Connexin 43 (Cx43) in human bladder tissue of urodynamically proven idiopathic detrusor overactivity to those of urodynamically stable bladders. STUDY DESIGN: We compared bladder biopsies of patients with detrusor overactivity and those with stable bladder analysing Cx43 message by RNA extraction and PCR amplification. All patients had multichannel urodynamics prior to the biopsies. RESULTS: We investigated the bladder biopsies of 15 female patients with and 15 patients without detrusor overactivity. Cx43 could be detected in nine patients of the detrusor overactivity group and in eight patients of the control group which was not statistically significant. 42 cycles of PCR were necessary to demonstrate Cx43 presence in the positive specimen. The presence of Cx43 was not consistent in the samples from the bladder dome and the side walls meaning there were Cx43 positive results in the dome and negative ones in the side walls of the same patient and vice versa. CONCLUSION: In conclusion, Cx43 is present in human bladder tissue both of overactive bladders and those of controls. However, it is expressed in very small amounts and is not always detectable. The role of Cx43 for the origin of detrusor overactivity remains unclear.

Laser-Sintern. Die Schluesseltechnologie des e-Manufacturing TM

e-Manufacturing™, das ist die schnelle, flexible und kostengünstige Fertigung von Produkten, Formen/Werkzeugen oder Modellen direkt aus elektronischen Daten. e-Manufacturing™ schließt Rapid Prototyping, Rapid Tooling oder Rapid Manufacturing ein, geht aber zugleich weit über den Gedanken der schnellen Verfügbarkeit hinaus. Zwar wird auch in Zukunft die schnelle Produktentwicklung eine immer wichtigere Rolle spielen, bei der e-Manufacturing™ für ein verkürztes Time to Market sorgt, Entwicklungskosten verringert und zur Risikominimierung beiträgt. Darüber hinaus entstehen aber auch neue Geschäftsmodelle, da Kleinserienproduktion, steigende Variantenvielfalt und eine individualisierte Produktion (Mass Customization) plötzlich möglich und wirtschaftlich sind und sich neue Logistikkonzepte wie (Spare) parts on demand entwickeln. Die neue Konstruktionsfreiheit des Laser-Sinterns ermöglicht neue Produktkonzepte. Minimale Einschränkungen durch das Fertigungsverfahren erlauben funktionelle Integration und die Fertigung des „Unmöglichen“, da kreisförmige und lineare Werkzeugbewegungen das Produktdesign nicht mehr beeinflussen bzw. limitieren. Auch die Fertigungskonzepte unterliegen einem Wandel und werden deutlich flexibler. Werkzeuglose Produktion, losgrößenangepasste Fertigung und dezentrale Fertigung on demand sind die Schlagworte der Zukunft. Der vorliegende Beitrag zeigt Beispiele für den erfolgreichen kommerziellen Einsatz von Laser-Sintern in allen Phasen des Produktlebenszyklus. Der Schwerpunkt liegt dabei auf der direkten Herstellung von Funktionsteilen in der Serienfertigung. Die entscheidenden Faktoren für eine erfolgreiche Einführung und Anwendung von e-Manufacturing™ werden diskutiert. Der Beitrag zeigt auf, wie die neuesten technologischen Innovationen im Laser-Sintern, speziell zur Produktivitätssteigerung, das Spektrum der Anwendungsfelder erweitern, in denen dieses Fertigungsverfahren kostengünstige Lösungen bietet.

New MLSB resistance gene erm(43) in Staphylococcus lentus

The search for a specific rRNA methylase motif led to the identification of the new macrolide, lincosamide, and streptogramin B resistance gene erm(43) in Staphylococcus lentus. An inducible resistance phenotype was demonstrated by cloning and expressing erm(43) and its regulatory region in Staphylococcus aureus. The erm(43) gene was detected in two different DNA fragments, of 6,230 bp and 1,559 bp, that were each integrated at the same location in the chromosome in several S. lentus isolates of human, dog, and chicken origin.

Nonlinear behaviour of conduction and block in cardiac tissue with heterogeneous expression of connexin 43

Altered gap junctional coupling potentiates slow conduction and arrhythmias. To better understand how heterogeneous connexin expression affects conduction at the cellular scale, we investigated conduction in tissue consisting of two cardiomyocyte populations expressing different connexin levels. Conduction was mapped using microelectrode arrays in cultured strands of foetal murine ventricular myocytes with prede fi ned contents of connexin 43 knockout (Cx43KO) cells. Corresponding computer simulations were run in randomly generated two-dimensional tissues mimicking the cellular architecture of the strands. In the cultures, the relationship between conduction velocity (CV) and Cx43KO cell content was nonlinear. CV fi rst decreased signi fi cantly when Cx43KO content was increased from 0 to 50%. When the Cx43KO content was ≥ 60%, CV became comparabletothatin100%Cx43KOstrands.Co-culturingCx43KOandwild-typecellsalsoresultedinsigni fi cantly more heterogeneous conduction patterns and in frequent conduction blocks. The simulations replicated this behaviour of conduction. For Cx43KO contents of 10 – 50%, conduction was slowed due to wavefront meandering between Cx43KO cells. For Cx43KO contents ≥ 60%, clusters of remaining wild-type cells acted as electrical loads thatimpairedconduction.ForCx43KOcontentsof40 – 60%,conductionexhibitedfractal characteristics,wasprone to block, and was more sensitive to changes in ion currents compared to homogeneous tissue. In conclusion, conduction velocity and stability behave in a nonline ar manner when cardiomyocytes expressing different connexin amounts are combined. This behaviour results from heterogeneous current-to-load relationships at the cellular level. Such behaviour is likely to be arrhythmogenic in various clinical contexts in which gap junctional coupling is heterogeneous.

Butyrate increases intracellular calcium levels and enhances growth hormone release from rat anterior pituitary cells via the G-protein-coupled receptors GPR41 and 43

Butyrate is a short-chain fatty acid (SCFA) closely related to the ketone body ß-hydroxybutyrate (BHB), which is considered to be the major energy substrate during prolonged exercise or starvation. During fasting, serum growth hormone (GH) rises concomitantly with the accumulation of BHB and butyrate. Interactions between GH, ketone bodies and SCFA during the metabolic adaptation to fasting have been poorly investigated to date. In this study, we examined the effect of butyrate, an endogenous agonist for the two G-protein-coupled receptors (GPCR), GPR41 and 43, on non-stimulated and GH-releasing hormone (GHRH)-stimulated hGH secretion. Furthermore, we investigated the potential role of GPR41 and 43 on the generation of butyrate-induced intracellular Ca2+ signal and its ultimate impact on hGH secretion. To study this, wt-hGH was transfected into a rat pituitary tumour cell line stably expressing the human GHRH receptor. Treatment with butyrate promoted hGH synthesis and improved basal and GHRH-induced hGH-secretion. By acting through GPR41 and 43, butyrate enhanced intracellular free cytosolic Ca2+. Gene-specific silencing of these receptors led to a partial inhibition of the butyrate-induced intracellular Ca2+ rise resulting in a decrease of hGH secretion. This study suggests that butyrate is a metabolic intermediary, which contributes to the secretion and, therefore, to the metabolic actions of GH during fasting.

Tôṣe'ôt ḥayyîm : sēfer kôlēl kōl ofnê tefillôt û-taḥanûnîm le-hitpallēl baʿad ha-ḥôlîm we-ham-mētîm ... bi-lšôn ʿivrî û-vi-lšôn aškenazz i

ʿal yedê Yiṣḥāq Ben-Aryê Yôsēf Dōv ...