Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain

Acid-sensing ion channels (ASICs) are Na⁺-permeable ion channels activated by protons and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation. At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3, ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly in nociception and proprioception, and the structure-function relationship of ASICs. However, there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons co-released with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in some pathologies such as epilepsy, mood disorders and Alzheimer''s disease.     

Batching of low-concentration anesthetics with evaporators used in apparatuses for inhalation anesthesia

The accuracy of the anesthetic vaporizers with modern vaporizing devices is complicated by necessity of providing small anesthetic vapor concentration for a wide range of gas flows, especially at small flows, and at use of a combination of inhalation anesthesia with intravenous one. Compliance with the requirements of the international standards concerning the accuracy of low-concentration anesthetic vapor batching also does not provide management of anesthesia depth at various stages of surgical operations. The problem is solved well by replacement traditional vaporizers with so-called barbotage ones equipped by adjustment of vapor concentration by modem electronic methods. It is even more promising to use direct injection of the liquid anesthetics into the respiratory contour of infusion pump. However, because individual sensitivity of patients to anesthetics is rather variable, these devices do not provide regulation of the depth of anesthesia. Therefore, stability rather than accuracy of batching of low-concentration anesthetics with evaporators used in apparatuses for inhalation anesthesia is of cardinal importance, Methods of objective instrumental evaluation of the depth of anesthesia require further research and implementation.     

Abrechnungsmodalität für die Privatliquidation leitender Klinikärzte im Hochschulbereich (Einschaltung externer Abrechnungsstellen)

Ohne Zusammenfassung     

Die Gebietsbezeichnung “Herzchirurgie” ist eine neue Arztbezeichnung i. S. des § 23 Abs. 4 WBO

Ohne Zusammenfassung     

Analysis of serious non‐AIDS events among HIV‐infected adults at Latin American sites

Objective

Acquired immune deficiency appears to be associated with serious non‐AIDS (SNA)‐defining conditions such as cardiovascular disease, liver and renal insufficiency and non‐AIDS‐related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Materials and methods

Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV‐associated factors on non‐AIDS‐defining conditions.

Results

Among 6007 patients in follow‐up, 130 had an SNA event (0.86 events/100 person‐years of follow‐up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non‐AIDS‐defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T‐cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/μL) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors.

Conclusions

The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.     

Stimulation of kainate toxicity by zinc in cultured cerebellar granule neurons and the role of mitochondria in this process

Zinc chloride (0.01 mM kept for 3 h) is not toxic to cultured cerebellar granule neurons (CGNs) while kainate (0.1 mM kept for 3 h) demonstrates some but very low toxicity towards these cells.Measurements of the relative intraneuronal zinc ion concentration showed that increase in [Zn²⁺]_i under the simultaneous action of ZnCl₂ and kainate was significantly stronger compared to their separate action. Simultaneous treatment of CGNs with kainate and zinc chloride caused the swelling of neuronal mitochondria and consequent intensive neuronal death, which was totally prevented by NBQX (an AMPA/kainate-receptors blocker) or ruthenium red (a mitochondrial Ca²⁺ uniporter blocker). These data imply that Zn²⁺ synergistically to kainate increase their separate toxic effects on mitochondria leading to rapid neuronal death.