Rotational behavior induced in rats by intranigral application of GABA-related drugs and GABA antagonists

GABA and GABA-related drugs such as muscimol, gamma-hydroxybutyric acid and baclofen injected unilaterally into the substantia nigra of rats elicited contraversive turning. Unilateral injections of picrotoxin and bicuculline produced either ipsi- or contraversive turning depending on the volume of vehicle. I.p. applied haloperidol did not abolish the muscimol-induced turning. This and the direction of rotational behavior suggests that the turning behavior elicited by GABA-related drugs is not mediated by the nigrostriatal dopaminergic tract.     

Cholinomimetics induce theta rhythm and reduce hippocampal pyramidal cell excitability

The actions of cholinomimetics and of physostigmine were tested on two parameters reflecting hippocampal activity, namely theta activity and pyramidal cell excitability. In rats pretreated with methylscopolamine and anaesthetized with urethane i.v. administration of the cholinomimetics oxotremorine and arecoline and the cholinesterase blocker physostigmine evoked theta wave activity in the hippocampus, which was blocked by scopolamine. Spectral analysis demonstrated that the frequency of the theta waves induced was dose-related, ranging from about 3 Hz to between 5 and 6 Hz. theta Activity could not be induced by arecoline in animals with large septal lesions. Pyramidal cell excitability is known to be increased by endogenous acetylcholine released from cholinergic fibres. In the present study, however, i.v. injections of oxotremorine, arecoline and physostigmine in doses that induce theta activity diminished the excitability of CA1 pyramidal cells in a dose-dependent manner, as judged by the reduction in the amplitude of the population spike and the dendritic epsp. These depressant effects were attenuated by scopolamine but not by methylscopolamine. The depressant effect of arecoline was attenuated in rats with extensive lesions in the medial septal area. The present findings demonstrate that exogenously administered cholinomimetics only partly mimic the action of endogenous acetylcholine in the hippocampus. The central sites of action of exogenously administered cholinomimetics for mediation of theta activity and alteration of pyramidal cell excitability remain to be elucidated.     

Differences in electrophoretic patterns of non-histone proteins from large and small nuclei of rat brain

Non-histone proteins from total and fractionated nuclei of brain and of total nuclei of liver have been extracted with a modified method of Gronow and Griffiths⁸ and separated by disc electrophoresis.Non-histone proteins extracted from total brain nuclei could be separated into 14 main bands based on molecular weight. With non-histone proteins extracted from total liver nuclei, only 12 bands were obtained. The comparison of both electrophoretic patterns indicated a limited tissue specificity for these proteins.Total brain and cortex nuclei were fractionated into large and small nuclei on a discontinuous sucrose gradient. The non-histone protein profiles of these two fractions for both total brain and cortex showed qualitative differences. In large nuclei non-histone proteins could be separated into 13 distinct bands, whereas only 10 bands were obtained for the small nuclei. In both large and small nuclei one specific band was found. Total brain and cortex gave similar protein profiles for the corresponding nuclear fractions.When total nuclei were prewashed with NaCl solution, 3.5% of total nuclear proteins could be extracted with 0.15M NaCl and 13% with 0.35M NaCl. One-half of the Gronow and Griffiths⁸ soluble non-histone proteins were solubilized during the 0.35M NaCl treatment.     

The MHC-haplotype influences primary, but not memory, immune responses to an immunodominant peptide containing T- and B-cell epitopes of the caprine arthritis encephalitis virus Gag protein

In this report, we describe a short peptide, containing a T helper- and a B-cell epitope, located in the Gag protein of the caprine arthritis encephalitis virus (CAEV). This T-cell epitope is capable of inducing a robust T-cell proliferative response in vaccinated goats with different genetic backgrounds and to provide help for a strong antibody response to the B-cell epitope, indicating that it may function as a universal antigen-carrier for goat vaccines. The primary immune response of goats homozygous for MHC class I and II genes showed an MHC-dependent partitioning in rapid-high and slow-low responses, whereas the memory immune response was strong in both groups, demonstrating that a vaccine based on this immunodominant T helper epitope is capable to overcome genetic differences.     

On the role of the baseline firing rate in determining the responsiveness of cingulate cortical neurons to iontophoretically applied substance P and acetylcholine

The relationship between baseline firing rate and the magnitude of excitatory responses to iontophoretically applied substance P (SP) and acetylcholine (ACh) was determined for neurons in the anterior cingulate cortex of the rat. Whereas the size of responses to ACh was positively correlated with the level of ongoing neuronal activity, no correlation, either positive or negative, could be demonstrated for responses to SP. It seems unlikely that the excitatory effects of SP in this brain area result from release of endogenous ACh.     

Reduced activity of locus coeruleus neurons in hypertensive rats

The influence of blood pressure on locus coeruleus (LC) neuronal activity was investigated in chloral hydrate anesthetized rats. Mean spontaneous firing rate of LC neurons was reduced by 25% in deoxycorticosterone acetate (DOCA-salt) treated Sprague-Dawley rats and by 19% in spontaneously hypertensive rats (SHR) as compared to their corresponding control animals. In acute experiments performed on normotensive rats, peripherally induced blood pressure changes elicited reciprocal changes in cell firing of the majority of LC neurons. The findings suggest that LC may have a role in long-term regulation of blood pressure.     

Diagnostic value of sonography in patients with suspected carpal tunnel syndrome: a prospective study

OBJECTIVE: To determine the diagnostic value of sonography in patients with suspected carpal tunnel syndrome (CTS). METHODS: We conducted a prospective study of 110 wrists in 74 consecutive patients with suspected CTS who had been referred to a tertiary care center. We determined the largest cross-sectional area of the median nerve at the carpal tunnel. Because of the lack of a universally accepted reference standard, we first examined the association of sonography with nerve conduction. Then, we compared sonography with a reference standard based on the combination of nerve conduction studies and signs and symptoms. Sonography and reference standard tests were performed independently and interpreted under blinded conditions. Based on a fitted receiver operating characteristic curve, we estimated likelihood ratios (LRs) and posttest probabilities for different cutoffs. RESULTS: There was a high concordance between sonography and nerve conduction. Based on the combined reference standard, a cutoff of 10 mm(2) resulted in approximately equal sensitivity and specificity, but only moderate LRs. A cutoff of <8 mm(2) had satisfactory power to rule out CTS: the fitted-negative LR was 0.13. Conversely, a cutoff of > or =12 mm(2) had excellent power to rule in CTS, with a fitted-positive LR of 19.9. For nerves > or =12 mm(2) and a pretest probability of 70% expected in patients with suspected CTS in tertiary care, we found a posttest probability of CTS of 98%. CONCLUSION: Depending on setting and purpose, different cutoff values for the largest cross-sectional area may be used to accurately rule in or rule out CTS. Using sonography as a first-line test may cost-effectively reduce the number of nerve conduction studies in patients with suspected CTS. A large-scale, randomized controlled trial is required to determine the effects of sonography on clinical outcomes, the number of nerve conduction studies performed, and the total cost.     

Non-invasive method to assess genotoxicity of nocodazole interfering with spindle formation in mammalian oocytes

Trisomies due to nondisjunction in oogenesis are still a major cause of genetic diseases in humans. In this study, we analysed spindle morphology of in vitro matured nocodazole-exposed mouse oocytes by novel non-invasive Polscope-microscopy, and compared images to those obtained by anti-tubulin immunofluorescence of fixed oocytes. Polscope revealed a reduction in the numbers of oocytes expressing a birefringent spindle, and alterations in spindle morphology at concentrations of nocodazole below those inducing detectable aberrations in immunofluorescence. Hyperploidy increased significantly at a concentration of 40 nM nocodazole in mouse metaphase II oocytes, similar to thresholds inducing nondisjunction in cultured human lymphocytes. In conclusion, Polscope represents a novel highly sensitive, non-invasive method to identify chemicals inducing severe spindle aberrations that predispose mammalian oocytes to nondisjunction. Polscope may provide information on the functionality of the spindle in experimental studies but is also compatible with clinical trials in human assisted reproduction due to its non-invasive nature.