Intracellular Ca2+ buffers disrupt muscarinic suppression of Ca2+ current and M current in rat sympathetic neurons.

The role of intracellular Ca2+ concentration ([Ca2+]i) in the muscarinic suppression of Ca2+ current and M-type K+ current has been investigated in isolated rat sympathetic neurons using the whole-cell patch-clamp technique and fura-2 fluorescence measurements. Muscarinic stimulation suppressed currents without raising [Ca2+]i. Nonetheless, intracellular bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) (11-12 mM), a Ca2+ chelator, reduced Ca2(+)-current suppression from 82 to 15%. For the latter, we explain the BAPTA action by a requirement for a certain minimum [Ca2+]i for continued operation of the pathway coupling muscarinic receptors to M-type K+ channels. The pathway coupling muscarinic receptors to Ca channels also showed some dependence on [Ca2+]i, but there may also be a blocking action of BAPTA that is independent of Ca2+ chelation.     

Effects of a long-distance run on cardiac markers in healthy athletes.

BACKGROUND: Running a marathon is a stressful event for athletes. Limited research exists on the role of cardiac markers during such a strenuous event. The aim of this study was to investigate detailed changes in cardiac markers before and after a long-distance run. METHODS: We studied 25 male and 2 female runners (age 34-64 years) who were running the Visé-Maastricht-Visé marathon. Blood samples were drawn just before and immediately after finishing the marathon. An additional blood sample was collected 24 h later. RESULTS: Running the marathon led to a significant increase in cortisol. This returned to baseline values 24 h after the marathon. There was a slight increase in brain natriuretic peptide (BNP); however, this was not statistically significant. On the contrary, the N-terminal fragment of BNP (NT-pro-BNP) was significantly increased immediately after the run and was normalized 24 h later in 26 out of 27 runners (96%). The magnitude of the transient elevations in BNP and NT-pro-BNP increased with the age of the athletes. Furthermore, in 9 out of 27 runners there was a significant increase in troponin T. However, in all these runners this increase was transient and troponin-T levels returned to baseline values 24 h after the marathon. CONCLUSIONS: Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage. It seems that the magnitude of the increase in BNP could serve as a marker of the biological age of the myocardium.     

Ausfallhonorar wegen Nichterscheinens zu einem Exklusiv-Termin

Abstrakt 1. Nimmt ein Patient einen ihm von seinem (Zahn-)Arzt einger?umten Exklusiv-Termin nicht wahr, obwohl er auf dessen Eigenschaft ausdrücklich hingewiesen wurde, so hat er dem (Zahn-)Arzt den Behandlungsausfall abzüglich eines angemessenen Eigenanteils des (Zahn-)Arztes zu ersetzen. 2. Die Ersatzpflicht tritt auch dann ein, wenn der Patient den Termin nicht in der in dem Behandlungsvertrag vorgesehenen Frist absagt. Eine hierfür seitens des (Zahn-)Arztes bestimmte Frist von zwei Tagen vor Behandlungsbeginn stellt sich für den Patienten grunds?tzlich auch nicht als unangemessene Benachteiligung i.S. des § 307 BGB dar. 3. Ein Anspruch des Arztes entf?llt auch bei nur mündlicher Vereinbarung nicht unter dem Gesichtspunkt des § 4 Abs. 5b BMV-Z, denn diese Vorschrift ist teleologisch dahin zu reduzieren, dass nur zahn?rztliche Honoraransprüche aus erfolgten Behandlungen schriftlich vereinbart werden müssen. Soweit es jedoch um einen vertraglichen Anspruch wegen einer Leistungsst?rung geht, vermag das Schriftformerfordernis des § 4 Abs. 5b BMV-Z grunds?tzlich nicht einzugreifen. (Leits?tze des Bearbeiters)     

Role of IL-2 in rat fetal thymocyte development

Early during rat thymus ontogeny, an important proportion of thymocytes expresses IL-2R and contains IL-2 mRNA. To investigate the role of the IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures (FTOC) under several experimental conditions. The IL-2 treatment initially stimulated the growth of thymocytes and, as a result, induced T cell differentiation, but the continuous addition of IL-2 to rat FTOC, as well as the anti-CD25 administration, resulted in cell number decrease and inhibition of thymocyte maturation. These results indicate that immature rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes T cell differentiation as a consequence of its capacity to stimulate cell proliferation. Modifications in TCR alpha beta repertoire and increased numbers of NKR- P1+ cells, largely NK cells, were also observed in IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells responded to IL-2 in two stages, early in thymus development and around birth, in correlation with the maturation of two distinct waves of thymic cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around birth, supporting a role for IL-2 in the increased proliferation of mature thymocytes observed in vivo in the perinatal period. Taken together, these findings support a role for IL-2 in rat T cell development.      

Life expectancy in British Marfan syndrome populations

A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome.     

The diagnostic value of the fibrinogen/fibrin fragment E antigen assay in clinically suspected deep vein thrombosis

We have evaluated the fibrinogen/fibrin fragment E antigen assay as a diagnostic test in patients with clinically suspected venous thrombosis by comparing the results of this assay with venography in 272 patients. The result of the fragment E antigen assay was elevated in 79 of 80 patients with positive venograms for recent venous thrombosis (sensitivity 99%) and within the normal range in 161 of 192 patients with normal venograms (specificity 84%). The fragment E assay was also evaluated in 130 medical and surgical controls without evidence of venous thrombosis by leg scanning and the test was found to be relatively nonspecific. However, in the patient group under study, a correct clinical diagnosis of no thrombosis, based on a normal fragment E result, was made in 161 of 162 cases (negative predictive value of 99%). Therefore, a normal test result effectively excludes a diagnosis of venous thrombosis in clinically symptomatic patients. The assay, as currently performed, is technically demanding and takes 24 hr to complete. Therefore, it will have to be simplified before it can be applied to clinical practice.     

Nitric oxide induction in a rat model of selective pancreatic ischemia and reperfusion

BACKGROUND/AIMS: Ischemia and reperfusion of the pancreas may be important in aggravating the course of acute pancreatitis. In a rat model of selective pancreatic ischemia and reperfusion, we studied plasma levels of nitric oxide and expression of nitric oxide synthase in the pancrease and lung. METHODOLOGY: Pancreatic ischemia was achieved by occlusion of the 4 main pancreatic arteries for 40 min; this was followed by a 7-hour reperfusion period (group A, 10 rats). Outcome measures were compared with those of animals undergoing a sham operation (group B, 10 rats). RESULTS: Pancreatic damage in group A animals was demonstrated by increased serum alpha-amylase and by macroscopic and microscopic evidence. Total nitric oxide synthase activity in pancrease and lung was higher than in shams [median: 0.73 vs. 0.54 pmol/mg protein/min in the pancreas (P = 0.0082); 1.38 vs. 0.68 pmol/mg protein/min in the lung (P = 0.023)]; this was mainly due to activation of the inducible isoform of the enzyme. There was an associated 58.2% increase in plasma levels of nitric oxide metabolites [from mean 55.0 to 131.6 mumol/L (P < 0.001)]. Immunohistochemistry confirmed expression of inducible nitric oxide synthase and nitric oxide-mediated oxidative damage (nitrotyrosine) in both pancreas and lung. CONCLUSIONS: Ischemia and reperfusion of the pancreas induces pancreatic damage, overexpression of inducible nitric oxide synthase and oxidative damage within the pancreas and lung.     

Intrahepatic portal occlusion by microspheres: a new model of portal hypertension in the rat.

Available experimental models of portal hypertension are based either on cirrhosis or externally applied portal vein constricting devices. A new method is described of raising portal pressure, which uses intraportally injected microspheres to block intrahepatic portal radicles, which has the advantages of retaining normal liver architecture and providing a more clinically relevant intrahepatic obstruction to portal flow. Measured aliquots of microspheres (15, 25, 50, 90 microns) or equivalent volumes of saline were injected into a peripheral portal tributary (caecal vein) of 22 normal rats. The resultant changes in arterial, portal, and splenic pulp pressures were monitored. Sequential microsphere injections produced graduated rises in portal pressure up to a peak of 18.5-22.5 mm Hg (8.7-12.4 mm Hg increase from basal), which declined gradually to a steady state pressure of 13.3-15.1 mm Hg (4.0-5.0 mm Hg increase). There was no significant difference between pressure increases produced by microspheres of differing sizes. It is concluded that portal hypertension can be produced acutely by blocking portal radicles with microspheres. The maximum pressure achieved, however, is substantially less than that obtained by total portal vein occlusion (mean: 57.6 mm Hg). This suggests the existence of functional intrahepatic portal systemic shunts not previously described in the normal liver.