Activation of neurokinin receptors modulates K and Cl channel activity in cultured astrocytes from rat cortex

Short application of the neurokinin receptor agonist substance P (SP) leads to a biphasic depolarization of astrocytes cultured from rat cortex. The rapid and transient depolarizing event lasted few seconds, the slow one several minutes. In some cells, only the slow depolarizing component was observed. During the slow depolarizing event, the sensitivity of the membrane potential for a change in the K+ gradient decreased, indicating a decrease in the relative K+ permeability of the membrane. The rapid SP-induced depolarization could be reversed, when the membrane potential was depolarized to about 0 mV by elevation of the extracellular K+ concentration, indicating a reversal potential close to the Cl- equilibrium potential. When the membrane was clamped close to the resting membrane potential using the whole-cell patch-clamp technique, SP induced a biphasic inward current with a similar time course as the SP-induced membrane depolarization. Evaluating current-to-voltage curves indicated a conductance decrease during the slow inward current with a reversal potential of the SP-dependent current close to the K+ equilibrium potential. The mean open time of single K+ channels, measured in the cell-attached configuration of the patch-clamp technique, decreased after application of SP. In contrast, the mean open time of single Cl- channels increased. We conclude that activation of neurokinin receptors in astrocytes modulates the activity of K+ and Cl- channels, leading to a complex depolarization of the membrane potential.     

Biodisk: A new device for closure of patent foramen ovale: A feasibility study in swine

Purpose: To evaluate the feasibility, effectiveness, and safety of a porcine small intestinal submucosa (SIS)‐covered Biodisk (BD) for the closure of patent foramen ovale (PFO) in swine. Methods: Twelve piglets (9–30 kg) with PFO ranging in size from 6 to 12 mm were used for the in vivo testing. The BD device consisted of two basic nitinol wire components covered with platinum coil, a flexible SIS‐covered ring, and an anchor. The BD was advanced through an 8‐Fr sheath from the femoral vein. Nine acute animals were used to test the BD for deployment, stability, immediate shunt closure, and device repositioning before or after its detachment. To assess retrievability, four devices were deployed and intentionally embolized into the RA (n = 2) and LA (n = 2). The effectiveness of the device was evaluated by angiocardiography. EKG was recorded before and after PFO closure for 3 hr. From the 12 animals, nine were acute and three were followed; one for 6 weeks, one for 12 weeks, and one for 16 weeks. Results: Successful device implantation was achieved in all animals with no shunting of contrast media observed during follow‐up in. One animal needed to have device repositioned for complete PFO occlusion because of suboptimal placement at the first attempt. The device was easily placed and retrieved before detachment in all nine animals in the acute study. None of the BDs spontaneously embolized during release or on follow‐up. EKG did not demonstrate arrhythmias during or after treatment. Four intentionally embolized BDs were easily retrieved with an Amplatz goose neck snare. Macroscopic and histologic evaluation of the three long‐term animals showed that devices were well incorporated in the atrial septum with complete shunt closure. The SIS showed progressive remodeling with the host cells. There was also progressive endothelization of the BD device. Conclusion: The BD device deployment is feasible, safe, and effective. Long‐term studies are needed to evaluate its long‐term effectiveness. © 2010 Wiley‐Liss, Inc.     

Pre-emptive therapy with azoles in lung transplant patients. Geneva Lung Transplantation Group.

Pulmonary fungal infection is diagnosed in up to 15-25% of lung transplant recipients and frequently bears a fatal outcome. This prospective uncontrolled study addresses the efficacy and safety of pre-emptive azole therapy against fungal infection in these patients. Fluconazole or itraconazole have been systematically used according to reported fungus sensitivity after the discovery of fungi in lower respiratory tract samples. Patients were treated until the bronchial suture was normal and the cultures of the following bronchoscopy remained negative. Fungi were found post-transplantation in the lower respiratory tract specimens of 26 out of 31 (84%) patients, predominantly Candida albicans (20 patients) and Aspergillus fumigatus (16 patients). Mycelia characteristic of Candida spp. or Aspergillus spp. were found in necrotic tissue at the bronchial suture of nine patients. The mean duration of the 38 treatments was 3.6+/-2.6 months (range, 0.5-12 months). After a median follow-up of 16 (range, 0-48) months, two cases of extended ulcerative and pseudo membranous Aspergillus fumigatus bronchitis were observed and healed under itraconazole treatment. In conclusion, pre-emptive azole therapy may be effective and well-tolerated in lung transplant patients where fungi are found in the airways or pleura.     

The role of interferons in neuroblastoma. 1: Antiproliferative effects]

Antiproliferative effects of interferon alpha, beta and gamma were investigated on several human neuroblastoma cell lines using the soft agar colony forming assay and the MTT-test. Investigations were carried out in order to prove whether there is any relationship between antiproliferative effects, inhibition of N-myc expression and the 2-5A system. Growth of neuroblastoma cells was inhibited by all three kinds of interferons in a concentration-dependent manner, however, rather high concentrations were necessary in some cell lines. Expression of N-myc oncogen was not inhibited by interferon-beta and no relationship between antiproliferative effects and the 2-5A system was observed. A vector containing a small N-myc fragment in antisense direction was constructed and transferred into the interferon insensitive human neuroblastoma cell line LS. After transformation, LS cells became sensitive to interferon beta: Proliferation as well as N-myc expression were inhibited and these processes are most probably associated with activation of the 2-5A system.     

Think Bone The Novel Paradigm of Central Bone Mass Control

Our understanding of the molecular physiology of the skeleton has been transformed by recent advances in human and mouse genetics and molecular endocrinology. Through the successful convergence of genetics and clinical observation, novel insights marking a breakthrough in the understanding of the molecular physiology of the skeletal system were gained. The paradigm that osteoblast and osteoclast function are mechanistically linked, being dogma in the bone field for decades, is overcome by experminental data showing that the maintenance of the skeletal system is, at least partially, controlled by the hypothalamus. Leptin was indentified as one key molecule in the central regulation of bone mass, and its importance was demonstrated across several species. Indeed, in vivo leptin signaling is able to overcome the deleterious effect of hypercortisolism and hypogonadism on the skeleton. This review presents a perspective on the data supporting the hypothesis of central bone mass control.     

Cotard’s syndrome: A review

Cotard’s syndrome is a rare disorder in which nihilistic delusions concerning one’s own body are the central feature. It is not listed as a specific disorder in the DSM-IV, as it is typically viewed as a part of other underlying disorders. However, it remains important to recognize the syndrome because specific underlying mechanisms are present, and prognostic and therapeutic consequences have to be taken into account. This review presents an up-to-date overview of Cotard’s syndrome, which was initially described more than a century ago.