Binocular suppression in cortical neurons

Summary Dichoptic presentation of patterns similar in shape but of very different contrast results in the perception of only the high contrast pattern (binocular suppression). When recording from binocular neurons of the cat visual cortex, we have found an effect which is strikingly similar to this perceptual phenomenon. If a high and a low contrast grating are presented simultaneously, one to each eye, the cell's response to the low contrast stimulus is suppressed.     

NO enhances presynaptic currents during cerebellar mossy fiber-granule cell LTP

Nitric oxide (NO) is a candidate retrograde messenger in long-term potentiation (LTP). The NO metabolic pathway is expressed in the cerebellar granule cell layer but its physiological role remained unknown. In this paper we have investigated the role of NO in cerebellar mossy fiber-granule cell LTP, which has postsynaptic N-methyl-d-aspartate (NMDA) receptor-dependent induction. Pre- and postsynaptic current changes were simultaneously measured by using extracellular focal recordings, and NO release was monitored with an electrochemical probe in P21 rat cerebellar slices. High-frequency mossy fiber stimulation induced LTP and caused a significant NO release (6.2 +/- 2.8 nM; n = 5) in the granular layer that was dependent on NMDA receptor as well as on nitric oxide synthase (NOS) activation. Preventing NO production by perfusing the NOS inhibitor 100 microM NG-nitro-l-arginine (L-NNA), blocking extracellular NO diffusion by 10 microM MbO2, or inhibiting the NO target guanylyl cyclase (sGC) with 10 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-dione (ODQ) prevented LTP. Moreover, the NO donor 10 microM 2-(N,N-diethylamino)-diazenolate-2-oxide.Na (DEA-NO) induced LTP, which was mutually occlusive with LTP generated by high-frequency stimulation, prevented by ODQ, and insensitive to NMDA channel blockade (50 microM APV + 25 microM 7-Cl-kyn) or interruption of mossy fiber stimulation. Thus NO is critical for LTP induction at the cerebellar mossy fiber-granule cell relay. Interestingly, LTP manipulations were accompanied by consensual changes in the presynaptic current, suggesting that NO acts as a retrograde signal-enhancing presynaptic terminal excitability.     

Effect of defective connective tissue on the formation of aneurysmal-like structures in the rat testicular artery

Microscopic aneurysmal-like structures (ALS) develop spontaneously in the convoluted rat testicular artery and have been previously proposed as a model relevant to cerebral aneurysms. The effect of defects in connective tissue fibres on ALS formation was investigated by microscopy using two approaches: (i) the study of the effect of β-aminopropionitrile (BAPN), an inhibitor of the cross-linking of elastic and collagen fibres, on the incidence, size and morphology of ALS in spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). The straight spermatic artery was studied for comparison. (ii) The determination of the incidence of spontaneous ALS in Brown Norway (BN) and Long Evans (LE) rats which are highly susceptible (BN) or resistant (LE) to the spontaneous rupture of the arterial internal elastic lamina. (i) BAPN increased the number and size of ALS in SHR and WKY rats and had no effect on the straight spermatic artery and (ii) ALS were more numerous and of greater size in BN than in LE rats. Taken together, these results show that defective connective tissue fibres may favour the formation and induce the enlargement of aneurysmal-like structures. By analogy, these data suggest that a lack of connective tissue fibre integrity may be of importance in cerebral aneurysm formation and development.     

Vaccination with streptococcal extracellular cysteine protease (interleukin-1β convertase) protects mice against challenge with heterologous group A streptococci

Virtually all clinical isolates of group A streptococci secrete a highly conserved extracellular cysteine protease that cleaves human fibronectin and vitronectin, and converts IL-1β precursor to biologically active IL-1β. Based on the high degree of gene conservation within the species and its role in host pathogenicity, it was postulated that antibodies to the cysteine protease would confer protective immunity against S. pyogenes infection. To test this hypothesis, Swiss CD1 mice were intraperitoneally administered either saline, rabbit IgG, or IgG from rabbits immunized with the protease, and challenged with a highly virulent (minimum lethal dose 10 cfu) clinical isolate of S. pyogenes expressing a heterologous cysteine protease. The results indicate that mice administered IgG from rabbits immunized with purified cysteine protease had significantly enhanced survival when compared with mice given either non-specific rabbit IgG (log rank test; χ²; p = 0.0195) or saline (log rank test; χ²; p = 0.0002). Moreover, mice actively immunized with the cysteine protease had a significantly longer time to death than the control group (log rank test; χ²; p = 0.0418). The results show that the cysteine protease elicits non-type-specific immunity to challenge with heterologous S. pyogenes.     

A COMPARATIVE STUDY OF TENIDAP, A CYTOKINE-MODULATING ANTI-RHEUMATIC DRUG, AND DICLOFENAC IN RHEUMATOID ARTHRITIS: A 24-WEEK ANALYSIS OF A 1-YEAR CLINICAL TRIAL

Tenidap is a novel anti-rheumatic drug that combines cytokinemodulation with cyclo-oxygenase inhibition. This 24-week, multicentre,double-blind, randomized study compared the clinical efficacy,biochemical effects and safety of tenidap 120 mg/day (once daily)with diclofenac 150 mg/day (50 mg t.i.d.) in the treatment of384 patients with active rheumatoid arthritis. After 24 weeks,improvement with tenidap was significantly greater than withdiclofenac for all five primary efficacy parameters, two ofthe four secondary efficacy parameters and 11 of the 13 ArthritisImpact Measurement Scales assessments. The superior efficacyof tenidap was apparent after 4 weeks of treatment with furtherimprovements observed by 24 weeks. The probability of discontinuationdue to lack of efficacy was significantly greater in the diclofenacgroup. Tenidap but not diclofenac was associated with significant,rapid and sustained reductions in C-reactive protein and serumamyloid A levels and with a significant reduction in plasmainterleukin-6. The nature and frequency of side-effects weresimilar in the two groups as was the discontinuation rate fortreatment-related safety reasons. Tenidap was associated withan equal incidence of elevated transaminases, but a higher incidenceof mild (     

Clinical and alimentary history of children attending a pediatric gastroenterology outpatient clinic with functional chronic constipation and its possible complications

In order to better understand the natural history of chronic functional constipation, a questionnaire was applied to 163 children and infants, before beginning standardized treatment. Median age (range) at start was 3 mo(0-108 mo) but age at arrival at the Pediatric Gastroenterology Unit was 53 mo(2-146 mo). In 62.4% of the cases symptoms began before or up to 3 mo after cow's milk introduction and rarely around (-/+ 6 mo) toilet training. Possible complications appeared progressively, often at preschool or school age or as the first noticeable manifestation: recurrent abdominal pain (61.1%), fecal soiling (45.4%), fecal blood (35%), enuresis (23.3%), vomiting (19%), urinary infection (17.9%), urinary retention (8.6%). Abdominal distension was rarely detected on physical examination and was usually discrete. In conclusion, children attended in Botucatu begin their constipation at an early age, frequently associated with weaning,and important complications may ensue along years. This evolution should be avoided by prevention and early treatment of constipation.     

Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.     

A psychometric-genetic study of schizotypal disorder

This study aimed to clarify the structure and the etiological constituents of schizotypal disorder (SPD) by directly interviewing pairs of twins. A latent class analysis was applied to each individual's outcome for specified SPD items, such that each subject's phenotype could be redefined in terms of individual probabilities of class membership. Intraclass correlations were then calculated for each twin pair, and a standard univariate twin model applied. The best latent class analysis solution encompassed a model with four latent classes (three latent classes of SPD subjects, one of non-SPD). The intraclass correlations revealed a moderate to high heritability for two out of three SPD classes and for the modal class (a class composed of subjects that possessed a conditional probability of belonging to any of the SPD classes). Model fittings revealed considerable variation in the extent to which the different classes of SPD were influenced by additive genetic constituents or non-genetic factors. Although these data confirm the importance of genetic contributors in determining liability to SPD and the schizophrenia spectrum, they indicate that there is a relationship between psychometric multidimensionality and etiological heterogeneity in SPD.