Inhibitory action of Ca2+ on spontaneous transmitter release at motor nerve terminals in a high K+ solution

The inhibitory effect of a high external Ca²⁺ ([Ca²⁺]_o) on spontaneous transmitter release in a high K⁺ solution (Gage and Quastel 1966; Birks et al. 1968) was studied at the frog neuromuscular junction, based on the hypothesis that an increased intracellular free Ca²⁺ ([Ca²⁺]_i) in the nerve terminal plays a key role in the depression. Three procedures were employed to increase [Ca²⁺]_i; increasing [Ca²⁺]_o, application of caffeine and tetanic nerve stimulation. All of these procedures increased m.e.p.p. frequency in normal Ringer. However, as the basic m.e.p.p. frequency was increased by raising the external K⁺ concentration (7–15 mM), their facilitatory effects on m.e.p.p. frequency decreased, disappeared and eventually reversed to depressant actions. Since a rise in the external K⁺ concentration would increase the steady state level of [Ca²⁺]_i, it is suggested that when the [Ca²⁺]_i is preset at a high level, manipulations so as to further increase [Ca²⁺]_i depress spontaneous release of transmitter. Possible mechanisms for this inhibition was discussed in relation to a question whether or not the rate of spontaneous transmitter release is a monotonic function of [Ca²⁺]_i.     

Interactions between taste receptors in the frog tongue

Summary Receptors sensitive to stimulation with dilute CaCl₂ solutions and located in different fungiform papillae of the frog tongue are cross-connected via branches of the glossopharyngeal nerve fibers to form chemical sensory units comprising on average about 3 papillae; often one or more papillae were found to be common to different units.The receptor response observed when single papillae were individually stimulated increased, when the strength of the stimulus was raised, at a much lower rate than that obtained by stimulating the whole tongue surface. This proves that the antidromic impulses travelling in the cross-connections linking different papillae result in an evident depression of the receptor response to CaCl₂.The possible functional significance of mutual interaction between the receptors in the frog tongue is discussed.This study was supported by grants from the Consiglio Nazionale delle Ricerche (Impresa di Elettrofisiologia) of Rome, Italy.     

The gap effect and inhibition of return: interactive effects on eye movement latencies

Three experiments are reported with two types of manipulations that are known to affect the latency with which subjects can initiate saccadic eye movements. The first manipulation involves the temporal relation between the offset of a visual fixation point and the onset of a peripheral target (the gap effect). The second manipulation involves the prior allocation and removal of visual attention (inhibition of return). In two experiments, the gap effect was smaller for saccades to previously attended locations than to previously unattended locations. The results suggest an important link between the two phenomena and provide new insights into the brain mechanisms underlying visual attention and eye movements.     

Cross-orientation inhibition in cat is GABA mediated

Summary Visual evoked potentials (VEPs) were recorded from cat cortex (area 17) before, during and after application of the GABA blocker bicuculline (iontophoretic or topical). The stimuli comprised a test sinusoidal grating, and a mask grating oriented either parallel or orthogonal to the test. Both test and mask alternated in contrast at different temporal frequencies. VEPs were averaged in synchrony with the test contrast reversal, so the mask did not contribute directly to the averaged VEP response. Before application of bicuculline, both parallel and orthogonal masks attenuated the amplitude of VEPs and changed the phase response, but in different ways. Orthogonal masks lowered the slope of the contrast response curve without affecting extrapolated threshold, while parallel masks caused the curve to shift to the right. Orthogonal masks increased the phase advance, while parallel masks eliminated it. During application of bicuculline, neither parallel nor the orthogonal masks attenuated VEP amplitudes. The results suggest that although the mechanisms for the action of parallel and orthogonal masks are clearly distinct, both are mediated by the GABA-ergic inhibitory system. Given this evidence, measurement of VEP contrast response curves may provide a simple non-invasive technique for monitoring visual inhibition in humans.     

Inhibition of human adrenal androgen secretion by ketoconazole

Summary The effect of ketoconazole on adrenal androgen secretion was examined in 15 patients with elevated serum androgens. In a dose of 600 mg per day orally ketoconazole inhibited the biosynthesis of all measured androgens. The mean reduction in serum levels of dehydroepiandrosterone sulfate was 32%, of dehydroepiandrosterone 54%, of androstenedione 52%, and of testosterone 43%; mean serum levels of cortisol only fell by 19%. The reduction in serum androgen levels was first significant 24 h after beginning of treatment and persisted as long as the drug was administered. We conclude that ketoconazole inhibits adrenal androgen biosynthesis more pronouncedly than cortisol biosynthesis. This might be of clinical benefit in the treatment of hirsutism and other states of androgen hypersecretion.Abbreviations CV coefficient of variation - MV mean value - SEM standard error of the mean - f female - m male - K ketoconazole - ACTH adrenocorticotropic hormone - DHEA dehydroepiandrosterone - DHEAS dehydroepiandrosterone sulfate - A androstenedione - T testosterone - F cortisol - P progesterone - H hirsutism - C Cushing's disease - EAS ectopic ACTH syndrome - ATU adrenal tumor     

High rate of false positives in blood donor screening for antibodies to hepatitis C virus

Summary Anti-hepatitis C virus antibody screening of blood donors in different countries revealed prevalences ranging from 0,4–1,4%. These results were obtained with an enzyme immunoassay based on a recombinant hepatitis C virus antigen. We applied a specific inhibition assay (neutralization assay) and a recombinant immunoblot assay to determine the specificity of positive reactions in the enzyme immunoassay.Of 2836 blood donor sera tested, 10 (0,35%) were reactive in the enzyme immunoassay, however, only 3 sera (0,1%) proved to be specifically anti-HCV positive in the inhibition assay. The recombinant immunoblot assay gave similar results. The prevalence of anti-hepatitis C virus antibodies among blood donors has been overestimated in recent publications. Furthermore the high rate of false positives in the enzyme immunoassay may explain reports claiming that only a minor part of EIA positive blood units transmitted the hepatitis C virus to recipients.The inhibition assay was also applied to sera of haemophiliacs and of patients with hepatopathy which had reacted positively in the anti-hepatitis C virus antibody enzyme immunoassay. The antihepatitis C virus specificity was confirmed for all sera from the haemophiliacs group (100%) and for 77% of the hepatopathy patients group. Thus, the anti-hepatitis C virus enzyme immunoassay has a high predictive value when it is used to screen groups with high risks of parenteral hepatitis C virus infection, however, its predictive value is very low when it is used for blood donor screening.Abbreviations EIA enzyme immunoassay - HCV hepatitis C virus - RIBA recombinant immunoblot assay - SOD superoxide dismutase     

Niedrig dosierte Acetylsalicylsäure (100 mg/Tag) nach aortokoronarer Bypassoperation

Summary A prospective, randomized, doubleblind, placebo-controlled trial was conducted to evaluate the efficacy of Acetylsalicylic Acid (ASS) (100 mg/d, starting 24 h after operation) on vein graft patency. Sixty of 88 patients having undergone surgery entered the study; in 24 of 31 patients in the placebo group and 22 of 29 patients in the ASS-group angiography was performed 4 months postoperatively. There were no significant differences between the groups with respect to age, number of diseased vessels or previous myocardial infarctions. Mean number of grafts per patient was 2,2 (placebo) and 1,8 (ASS) for proximal anastomoses (p<0.10) and 3.4 (placebo) and 2.6 (ASS) for distal anastomoses (p<0.05). Graft occlusion rate for proximal anastomoses was less in the ASS-group, 10% (4/40), as compared with placebo 32% (17/53) (p<0.05). Graft occlusion rate for distal anastomoses was also less in the ASS group, 19% (11/57) as compared to 35% (28/81) in the placebo group (p<0.10). All grafts were patent in 16/22 patients in the ASS group but only in 9/24 in the placebo group (p<0.05). On designation of patients without postoperative angiograms but cardiovascular events as well as those with at least one graft occluded as failures, the incidence of the latter was 9/29 in the ASS group and 20/31 in the placebo group (p<0.05). Early postoperative bleeding was similar in both groups, no side effects of ASS were observed. In this trial with initiation of low — dose ASS therapy 24 h after operation, antiplatlet therapy reduced the graft occlusion rate significantly.

Teile dieser Studie wurden auf der 49. Tagung der Deutschen Gesellschaft für Herz- und Kreislaufforschung in Mannheim im April 1983 [32] und auf der 89. Tagung der Deutschen Gesellschaft für Innere Medizin, Wiesbaden, April 1983 [18] vorgetragen. Mit Unterstützung der Deutschen Forschungsgemeinschaft     

Inhibitory interaction between the vestibulo-ocular reflexes arising from semicircular canals of rabbits

Summary In anesthetized albino rabbits, electric pulse stimulation was applied to ampullary branches of the vestibular nerve. Reflex discharges evoked from a canal in an extraocular muscle were depressed very effectively by conditioning stimulation at a certain other canal. The present systematic survey revealed that this reflex depression occurred specifically in 3 combinations of conditioning and testing canals; 1. anterior and posterior canals of the same side; 2. anterior and posterior canals of the opposite sides; and 3. horizontal canals of the two sides. Occurrence of postsynaptic inhibition in oculomotor neurons, on the other hand, was indicated by appearance of slow muscle potentials in extraocular muscles. It was confirmed that this motoneuronal inhibition did not contribute to the reflex depression in the above combination (1). Even in combinations (2) and (3), the accompanying motoneuronal inhibition was eliminated by adjusting intensities of canal stimuli or by severing its pathway in the medulla, or it was discriminated from the reflex depression by their different latencies and time courses. Hence, it was concluded that the reflex depression was attributable, at least largely, to non-motoneuronal inhibition, presumably postsynaptic inhibition at relay neurons for vestibulo-ocular reflexes. Slow muscle potentials evoked from a canal were also used as testing responses, but their depression could not be detected after conditioning at other canals.     

Bulbospinal inhibition of PAD elicited by stimulation of afferent and motor axons in the isolated frog spinal cord and brainstem

Summary 1. In the isolated spinal cord and brainstem of the frog, stimulation of the brainstem (BS) with trains of 3–4 pulses at 60–400 Hz produced dorsal root potentials (DRPs). The lowest threshold sites eliciting DRPs were located at the level of the obex up to about 2.5 mm rostrally, 0.5–1.2 mm laterally, between 0.5 and 1.6 mm depth. This region corresponds to the bulbar reticular formation (RF). 2. Stimulation of the RF with strengths below those required to produce DRPs, very effectively inhibited the DRPs produced by stimulation of a neighboring dorsal root (DR-DRPs) as well as the DRPs produced by antidromic stimulation of the central end of motor nerves (VR-DRPs). The inhibition was detectable 20 ms after the first pulse of the conditioning train, attained maximal values between 50 and 100 ms and lasted more than 250ms. 3. Stimulation of the bulbar RF increased the negative response (N₁ response) produced in the motor pool by antidromic activation of motoneurons. The time course of the facilitation of the N₁ response resembled that of the reticularly-induced inhibition of the VR-DRPs and DR-DRPs. 4. The present series of observations supports the existence of reticulospinal pathways that are able to inhibit the depolarization elicited in afferent fibers by stimulation of other afferent fibers or by antidromic activation of motor axons. This inhibition appears to be exerted on the PAD mediating interneurons and is envisaged as playing an important role in motor control.