Junctional and extrajunctional acetylcholine receptors in normal and denervated frog muscle fibres

Summary Ionic channel properties of acetylcholine receptors located in, in the vicinity of, or far away from a frog neuromuscular junction were investigated by noise analysis of drug induced current fluctuations. For drugs applied to the junction, in certain cases two Lorentzian curves were necessary to describe the data. It is postulated that the reason for this observation is that a contribution from perijunctional receptors was being observed. The conductance of a single channel in the junction was independent of the nature of the agonist and had an average value of 17.9 pS (temperature range 8–25°C, solution buffered with Tris). After denervation for 21 days the conductance γ was 7.5 pS at extrajunctional locations. In the close neighbourhood of the junction (perijunctional receptors) values were found between 4 and 19 pS. The mean value of the open channel life-time τ in the endplate exposed to acetylcholine was 2.4 ms at 8–11°C. This value was 0.90 ms with carbachol, 0.50 ms with succinylcholine, 0.28 ms with decamethonium and 0.45 ms with nicotine. The receptors outside the endplate exhibited τ-values which at a given temperature were 2–3 times larger than those at the endplate. Raising the temperature to 23°C reduced all τ-values by factors of 2–3. It is concluded that at least two types of ACh-receptors with different properties exist in the muscle membrane, possibly produced by ACh-receptive units in different states of aggregation. This work was supported by the Deutsche Forschungsgemeinschaft, SFB 38, Project N     

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.      

Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.     

Three novel PROC gene lesions causing protein C deficiency

Hallam PJ, Mannucci P, Tripodi A, Bevan D, Laursen B, Tengborn L, Wacey A, Cooper DN. Three novel PROC gene lesions causing protein C deficiency. Clin Genet 1998: 54: 231–233. 0 Munksgaard, 1998
Missense mutations. three of them novel (Am210→Val, Asn248→ Ile, Ah355→Val), were found in the protein c ( PROC ) genes of 7 patients with inherited protein C deficiency associated with venous thrombosis. Comparison with the phenotypic effects of mutations in the analogous residues of factor IX causing hdernophilia B and the use of molecular modelling has provided explanations as to how these lesions might alter either the structure, function or secretion of the protein C molecules encoded.     

Pseudosickling of hemoglobin Setif

Hemoglobin Setif produces pseudosickling of red cells in vitro; the nature of the process and the conditions that "trigger" it are unknown. Studies of red cells, hemolysates, purified hemoglobin solutions, and artificial mixtures of Hb A and Setif suggest that pseudosickling is produced by intracellular crystallization of insoluble hemoglobin. Increased tonicity of the suspending medium accentuates the process, probably by causing a rise in intracellular hemoglobin concentration. If precipitates from A/Setif mixtures are analyzed, they always contain Hb A, suggesting an unusual mechanism for the process. Despite the fact that osmolality in the renal medulla is similar to that which produces pseudosickling in vitro, carriers do not have renal dysfunction of the type found in patients with sickle cell disease.     

Wife abuse prevention: Effects of information on attitudes of high school boys

Six classes of students attending private parochial high schools were matched according to geographic and grade level variables and were randomly assigned as intact groups to view either a film concerning wife abuse or a neutral control film. The experimental film had no significant impact on attitude ratings given for the two most common student-generated situations of abuse: the intoxicated husband and the unfaithful wife. Correlational assessments between demographic variables and attitude ratings revealed that greater suspicion of abuse was associated with higher justifiability ratings for the intoxicated husband situation. Estimations of higher frequencies of spouse abuse were associated with higher justifiability ratings for the unfaithful wife situation. Results are discussed in light of current wife abuse education programs and prevention strategies.     

Mundgesundheitskompetenz von Menschen mit Migrationshintergrund – Erste Auswertungen der MuMi-Studie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Erste Studien heben den Migrationshintergrund von Menschen in Deutschland als eigenständigen Risikofaktor für eine...     

Is there clinical evidence to support autologous matrix-induced chondrogenesis (AMIC) for chondral defects in the talus? A systematic review and meta-analysis

BackgroundThe aim of this study is to systematically review the literature on clinical outcomes of patients who have undergone autologous matrix-induced chondrogenesis (AMIC) for treatment of osteochondral lesions of the talus (OCL) and compare the studies’ outcomes.MethodsPubmed and Embase were searched in January 2020 for articles concerning OCL surgery. Studies were included if they had a minimum 1-year follow-up and the primary measures were functional outcomes. The meta-analysis compared the Visual Analogic Score (VAS), the American Orthopedic Foot and Ankle Score (AOFAS), and the Foot Function Index (FFI) between baseline and follow-up of 1?2 years, and 3?5 years. A random effects model was used to evaluate outcome changes.ResultsThe search returned 15 studies, with a total of 492 patients. The VAS improved 4.45 and 4.6 points from baseline to the 1?2 year and 3?5 year follow-up, respectively (p < 0.001). AOFAS improved 31.59 and 32.47 points from baseline to the 1?2 year and 3?5 year follow-up, respectively (p < 0.001). The FFI showed a significant improvement of 30.93 points from baseline to year 3?5 (p < 0.001). A total of 6 patients with revision surgeries have been reported within the follow up period. It was not possible to correlate clinical features like lesion size, surgical approach, and bone marrow stimulation technique to the reported outcome.ConclusionSurgical treatment of OCL via the AMIC procedure provided significant improvement in the functional outcome and pain scores when compared to the pre-operative values. Improvements were observed up to 5 years post-operatively.     

Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application

Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t _1/2), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g t _1/2 values were 5.5 and 4.7 h, respectively, mean-g t _max data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g C _max ^maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag,t _max, andC _max. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite reduced benperidol were found to be very low.