Pharmacokinetics of repeated doses of misoprostol

BACKGROUNDMisoprostol is widely used in obstetrics and gynaecology for medical abortion, cervical priming and induction of labour. To aid the design of effective and safe regimens, we have investigated the pharmacokinetic parameters after the vaginal or sublingual administration of repeated doses of 400 g of misoprostol.METHODSWomen undergoing termination of pregnancy by suction evacuation were randomized to receive 400 g of sublingual or vaginal misoprostol every 3 h for five doses. Venous blood was taken at 180, 200, 240, 360, 380, 420, 540, 560, 600, 720, 740, 780 and 900 min after the first dose of misoprostol for determination of the plasma level of misoprostol acid (MPA).RESULTSThe peak plasma levels of MPA decreased with successive doses of vaginal misoprostol, whereas the peak plasma levels were similar with successive doses of sublingual misoprostol. After the third dose, the peak plasma levels of MPA after sublingual misoprostol were significantly higher than those after vaginal administration. After the final dose, the area under the MPA concentration-time curve after sublingual administration was significantly higher than that after vaginal misoprostol (P < 0.031). However, subgroup analysis in the vaginal administration group showed that the progressive decline in the peak plasma levels of MPA occurred only in women with significant vaginal bleeding.CONCLUSIONSThe peak plasma level of MPA after each dose of misoprostol is higher and the bioavailability is also greater after sublingual administration, compared with that after vaginal administration, of repeated doses of misoprostol. The difference was probably due to the reduction in absorption of vaginal misoprostol in the presence of significant vaginal bleeding.postprin

Localization of the succinate receptor in the distal nephron and its signaling in polarized MDCK cells

When the succinate receptor (SUCNR1) is activated in the afferent arterioles of the glomerulus it increases renin release and induces hypertension. To study its location in other nephron segments and its role in kidney function, we performed immunohistochemical analysis and found that SUCNR1 is located in the luminal membrane of macula densa cells of the juxtaglomerular apparatus in close proximity to renin-producing granular cells, the cortical thick ascending limb, and cortical and inner medullary collecting duct cells. In order to study its signaling, SUCNR1 was stably expressed in Madin-Darby Canine Kidney (MDCK) cells, where it localized to the apical membrane. Activation of the cells by succinate caused Gq and Gi-mediated intracellular calcium mobilization, transient phosphorylation of extracellular regulated kinase (ERK)1/2 and the release of arachidonic acid along with prostaglandins E2 and I2. Signaling was desensitized without receptor internalization but rapidly resensitized upon succinate removal. Immunohistochemical evidence of phosphorylated ERK1/2 was found in cortical collecting duct cells of wild type but not SUCNR1 knockout streptozotocin-induced diabetic mice, indicating in vivo relevance. Since urinary succinate concentrations in health and disease are in the activation range of the SUCNR1, this receptor can sense succinate in the luminal fluid. Our study suggests that changes in the luminal succinate concentration may regulate several aspects of renal function

Identifikacija biološki nerazgradivih zagađivača u riječnoj vodi

Over 100 non-biodegradable organic compounds, accumulated on a carbon filter of a Rhine waterworks, were isolated and identified by means of combined gas chromatography - mass spectrometry. The identified pollutants belong to five different classes: aliphatic as well as aromatic chlorinated hidrocarbons, nitro aromatic compounds, aromatic ethers, tert-butyl substituted phenols and phthalic acid esters. The potential toxicological hazard of the non-biodegradable organic compounds is briefly discussed.Biološki nerazgradivi organski spojevi djeluju nepovoljno na kvalitetu riječne vode koja služi za ljudsku upotrebu i prouzrokuju sekundarne efekte utječući na ekologiju rijeke. Ti se biološki nerazgradivi organski spojevi nakupljaju na ugljenim filtrima vodovoda. Za identifikaciju biološki nerazgradivih organskih spojeva, uzorak ugljenog filtra njemačkog vodovoda s donjeg toka rijeke Rajne, ekstrahiran je s organskim otapalima. Ekstrakti su separirani kromatografskim tehnikama te identificirani pomoću spektrometra masa vezanog uz plinski kromatograf. Neovisno o tome spojevi su identificirani mjerenjem vremena zadržavanja te pomoću infracrvene spektroskopije nakon hvatanja uzorka s maksimuma. Identificirane je više od 100 organskih spojeva. Većina pripada klasama kloriranih alifatskih i aromatskih ugljikovodika, aromatskih nitrospojeva i terc-butil supstituiranih aromatskih ugljikovodika

Limiter lock systems at TEXTOR: flexible tools for plasma-wall investigation

Limiter lock systems on the top and the bottom of the TEXTOR vessel are essential elements for experimental investigations of plasma-wall interaction in a tokamak. The lock systems are designed as user facilities that allow the insertion of wall elements (limiter) and tools for diagnostic (electrical probes, gas injection) without breaking the TEXTOR vacuum. The specially designed holder on top of the central carrier and a powerful vacuum pump system permit the exchange of components within similar to1 h. Up to ten electrical signals, four thermocouples, and a gas supply can be connected at the holder interface. Between discharges, the inserted component can be positioned radially and turned with respect to the toroidal magnetic field. Additionally, the central carrier is electrically isolated to apply bias voltages and currents up to 1 kV and 1 kA, respectively.An important feature of the lock system is the good access for optical spectroscopic observation of the inserted components in the vicinity of the edge plasma. The whole spectrum from ultraviolet to infrared is covered by spectrometers and filters combined with cameras. Toroidally and poloidally resolved measurements are obtained front the view on top of the probes while the tangential poloidal view delivers radially and toroidally resolved information.A programmable logic controller (Simatic S5) that is operated inside the TEXTOR bunker and from remote locations outside the concrete wall drives all possible features of the lock system