Histamine release after intravenous application of short-acting hypnotics. A comparison of etomidate, Althesin (CT1341) and propanidid

The subject of histamine release was investigated in 16 volunteers by means of plasma histamine determination after the administration of etornidate, Althesin, propanidid, and Cremophor EL. Althesin and propanidid caused release of histamine in various degrees of frequency. Blood pressure changes were rather pronounced with both anaesthetic agents; tachycardia reached its maximum in the first and second minute, which seems to be an argument against histamine release as the underlying cause of this reaction. Histamine was, indeed, only released to such an extent (with the exception of one borderline case) that no clinical symptoms other than secretion of gastric juice and erythema were to be expected. After the application of etomidate and Cremophor EL an increase in plasma histamine was not detectable. Changes in the differential blood picture in terms of a decrease in basophils only occurred after Althesin and propanidid; not, however, after etomidate and Cremophor EL. Etomidate is, therefore, the first hypnotic drug for intravenous application which is unlikely to cause chemical histamine release

Influence of steep Trendelenburg position and CO2 pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during robotic prostatectomy

The steep (40 degrees) Trendelenburg position optimizes surgical exposure during robotic prostatectomy. The goal of the current study was to investigate the combined effect of this position and CO2 pneumoperitoneum on cardiovascular, cerebrovascular, and respiratory homeostasis during these procedures. Physiological data were recorded during the whole surgical procedure in 31 consecutive patients who underwent robotic endoscopic radical prostatectomy under general anaesthesia. Heart rate, mean arterial pressure, central venous pressure, Sp(o2), Pe'(co2), P-Plat, tidal volume, compliance, and minute ventilation were monitored and recorded. Arterial samples were obtained to determine the arterial-to-end-tidal CO2 tension gradient. Continuous regional cerebral tissue oxygen saturation (Sct(o2)) was determined by near-infrared spectroscopy. Although patients were in the Trendelenburg position, all variables investigated remained within a clinically acceptable range. Cerebral perfusion pressure (CPP) decreased from 77 mm Hg at baseline to 71 mm Hg (P=0.07), and Sct(o2) increased from 70% to 73% (P < 0.001). Pe'(co2) increased from 4.12 to 4.79 kPa (P < 0.001) and the arterial-to-Pe'(co2) tension difference increased from 1.06 kPa in the normal position to a maximum of 1.41 kPa (P < 0.001) after 2 h in the Trendelenburg position. The combination of the prolonged steep Trendelenburg position and CO2 pneumoperitoneum was well tolerated. Haemodynamic and pulmonary variables remained within safe limits. Regional cerebral oxygenation was well preserved and CPP remained within the limits between which cerebral blood flow is usually considered to be maintained by cerebral autoregulation

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque

There are substantial differences across species in the organisation and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration 'thin' spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the expression of Kv3.1b in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labelled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons

Sectioning and Counting of Motor Neurons in the L3 to L6 Region of the Adult Mouse Spinal Cord

Histology is the study of the microscopic structure of tissues. This protocol permits the generation of frozen transverse sections of lumbar spinal cord regions L3 to L6. It enables counting of murine ventral horn lumbar motor neurons in a reproducible manner. Methods include spinal column dissection, hydraulic extrusion, and histological processing. The preparation for cryo-sectioning includes embedding lumbar spinal cord in optimal cutting temperature (OCT) medium. The correct orientation of the tissue is critical as calculating the amount of tissue to discard saved time overall. Specific details regarding section thickness and mounting are described. These requirements not only allow optimum coverage of specific regions but also ensure that no individual motor neuron was counted twice. The Nissl bodies of the motor neurons were stained using gallocyanin. The sections obtained are all of a comparable area and quality assurance is consistent. The specificity of the staining enables the scientist to identify and reliably quantify lumbar motor neurons. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Euthanasia of mouse and isolation of spinal cord. Basic Protocol 2: Hydraulic extrusion of the spinal cord. Basic Protocol 3: Identification of the lumbar region. Basic Protocol 4: Embedding cord in OCT. Basic Protocol 5: Collection of frozen sections onto slides. Basic Protocol 6: Gallocyanin staining. Basic Protocol 7: Motor neuron counting

Eine neue Methode zur Gewinnung von 1-Hydrazino-phthalazin

Das 4-Chlor-1-hydrazino-phthalazin(III), das in guter Ausbeute uber drei Synthesestufen aus Phthalsaureanhydrid erhalten wird, liisst sich hydrogenolytisch an Palladium-Katalysatoren glatt zum 1-Hydrazinophthalazin(VI) entchlorieren. Analog verliiuft auch die Hydrogenolyse von 4-Chlor-1-(2H) phthalazinon(IV) zum 1-(2H) Phthalazinon(V). Bei diesen Hydrogenolysen werden keine Nebenreaktionen festgestellt

Tolerance and safety evaluation of N, N-dimethylglycine, a naturally occurring organic compound, as a feed additive in broiler diets

N,N-dimethylglycine (DMG) is a tertiary amino acid that naturally occurs as an intermediate metabolite in choline-to-glycine metabolism. The objective of the present trial was to evaluate tolerance, safety and bioaccumulation of dietary DMG in broilers when supplemented at 1 g and 10 g Na-DMG/kg. A feeding trial was conducted using 480 1-d-old broiler chicks that were randomly allocated to twenty-four pens and fed one of three test diets added with 0, 1 or 10 g Na-DMG/kg during a 39 d growth period. Production performance was recorded to assess tolerance and efficacy of the supplement. At the end of the trial, toxicity was evaluated by means of haematology, plasma biochemistry and histopathology of liver, kidney and heart (n 12), whereas bioaccumulation was assessed on breast meat, liver, blood, kidney and adipose tissue (n 8). Carcass traits were similar between the control and 1 g Na-DMG/kg feed groups (P.0·05), but the feed:gain ratio was significantly improved at 1 g Na-DMG/kg feed compared with the control or the 10-fold dose (P¼0·008). Histological examinations showed no pathological effects and results of haematology and plasma biochemistry revealed similar values between the test groups (P.0·05). Bioaccumulation occurred at the 10-fold dose, but the resulting DMG content in breast meat was comparable with, for instance, wheat bran and much lower than uncooked spinach. In conclusion, DMG at 1 g Na-DMG/kg improved the feed:gain ratio in broilers without DMG being accumulated in consumer parts. Furthermore, dietary supplementation with DMG up to 10 g Na-DMG/kg did not induce toxicity or impaired performance in broilers

Behavioral and Other Phenotypes in a Cytoplasmic Dynein Light Intermediate Chain 1 Mutant Mouse

The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system

Functional studies of signaling pathways in peri-implantation development of the mouse embryo by RNAi

BACKGROUND: Studies of gene function in the mouse have relied mainly on gene targeting via homologous recombination. However, this approach is difficult to apply in specific windows of time, and to simultaneously knock-down multiple genes. Here we report an efficient method for dsRNA-mediated gene silencing in late cleavage-stage mouse embryos that permits examination of phenotypes at post-implantation stages. RESULTS: We show that introduction of Bmp4 dsRNA into intact blastocysts by electroporation recapitulates the genetic Bmp4 null phenotype at gastrulation. It also reveals a novel role for Bmp4 in the regulation the anterior visceral endoderm specific gene expression and its positioning. We also show that RNAi can be used to simultaneously target several genes. When applied to the three murine isoforms of Dishevelled, it leads to earlier defects than previously observed in double knock-outs. These include severe delays in post-implantation development and defects in the anterior midline and neural folds at headfold stages. CONCLUSION: Our results indicate that the BMP4 signalling pathway contributes to the development of the anterior visceral endoderm, and reveal an early functional redundancy between the products of the murine Dishevelled genes. The proposed approach constitutes a powerful tool to screen the functions of genes that govern the development of the mouse embryo