P. Tavares

Photosensitivity to piroxicam: absence of cross‐reaction with tenoxicam

We studied 2 groups of patients. One group or 10 patients had a photosensitive eruption to piroxicam. Another group of 24 patients had positive patch test reactions to thimerosal and thiosalicylie acid and had never taken piroxicam or tenoxicam. Patients were patch tested with thimerosal 0.1% pet., thiasalicylic acid 0.1% pet., salicylic acid 2.0% pet., piroxicam 1 and 5% pet. and tenoxicam 1 and 5% pet. photopatch tests were also performed with piroxicam and tenoxicam. All 10 patients with photosensitivity to piroxicam had positive patch tests to thiosalicylic and thiosalicylic acid and 9 of them had positive photopatch tests to ptroxicam. 20 out of 24 patients with positive patch tests to thiosalicylic acid also had positive photopatch tests to Piroxicam. All the patients tested with salicylic add were negative. Out of the 29 patients with positive photopatch tests to piroxicam, none reacted to tenoxicam. In countries with a high incidence of contact sensitivity to thimerosal/thiosalicylic acid, the use of piroxicam should be avoided and replaced by tenoxicam, a drug without reported photosensitivity

Catecholamine and MHPG plasma levels, platelet MAO activity, and3H-imipramine binding in heroin and cocaine addicts

AbstractThis work evaluated in a population of heroin and heroin plus cocaine human addicts:1.Norepinephrine (NE), epinephrine (Epi), and 3-methoxy-4-hydroxyphenylglycol (MHPG) (the principal metabolite of brain NE) plasma levels;2.Monoamine oxidase (MAO) activity; and3.3H-imipramine specific binding to the amine carrier in platelets. NE plasma levels were significantly lower in the short-term heroin user groups (1–3 and 4–6 yr), a finding not observed in both the long-term heroin user (>6 yr) and heroin plus cocaine user (>6 yr) groups. Epi levels changed in a similar manner, except that a significant increase was noted in heroin plus cocaine abusers. Conversely, dopamine and MHPG plasma levels increased with the duration of heroin use, and even more with cocaine abuse. Platelet MAO activity increased in all groups. Specific3H-imipramine binding sites showed an increase after 3 yr of heroin abuse and in all heroin plus cocaine addicts. In conclusion, short-term use of heroin decreases NE or Epi release, but with prolonged use, a slow adpatation occurs. In contrast, cocaine inhibits the neuronal Epi uptake, even in a situation of long duration of abuse. Probably the amine levels additionally regulate the amine carrier, resulting in changes that show a different pattern from major depression. These drugs of abuse may also influence directly or indirectly related enzymatic systems.

Influence of 0.1 or 0.2% cholesterol-enriched diets on the induction of atherosclerosis and aorta reactivity in vitro

Current knowledge of atherogenesis is largely based on animal models of hypercholesterolemia, which rarely show changes similar to the lesions described in humans. We studied the influence of two low cholesterol-enriched diets on the development of anatomopathologic lesions and on the reactivity of the isolated aorta in rabbits. Compared with controls (rabbits fed a normal diet), a 0.1% cholesterol-enriched diet over a 6- or 9-month period produced increases of the 5-hydroxytryptamine (5-HT)-induced contractile responses, as well as a decreases in acetylcholine (ACh)-induced relaxing response (endothelium-dependent, through the production of NO). Noradrenaline (NA)-induced contractions and relaxations elicited by sodium nitroprusside (SNP; endothelium independent) were not significantly modified. Because at 6 months, significant anatomopathologic intimal early lesions were not found, functional endothelial changes can explain such findings. There was a defect in NO synthesis, release, or diffusion; 5 HT, but not NA, may be responsible for inducing NO production. In 0.2% cholesterol-fed rabbits at 4 and 12 weeks, increases of 5-HT- and NA-induced contractile responses were found. In both cases, there was a decrease of ACh-induced relaxing effect, whereas responses to SNP remained unchanged. Intimal early and advanced lesions were present at both the 4- and 12-week periods. These data suggest abnormalities of the NO system. The effects obtained with NA may be explained by a possible decrease of catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO) activities or both or by decreased amine uptake. The extent to which NA may induce NO production is small, because changes in NA-induced contractions are verified only in the presence of significant alterations in the endothelium. The use of a 0.2% cholesterol diet for a short time may induce atherosclerotic lesions, whereas the 0.1% cholesterol diet for a 9-month period, besides being closer to the human diet, allows the detection of functional abnormalities before the evidence of structural lesions.

Circadian and seasonal variation of endogenous ubiquinone plasma level

Coenzyme Q10 (CoQ10) or ubiquinone, a redox component of the mitochondrial electron transport chains, is a powerful antioxidant and membrane stabilizer that may prevent cellular damage during myocardial ischemia and reperfusion therapy. Coenzyme Q10 has been used primarily as an adjuvant therapy for some cardiomyopathies. However, one of the main problems in CoQ10 administration is the high variability of endogenous plasma and tissue levels, which seems to be dependent on several factors. This work explores temporal 24h and seasonal variation as well as gender and racial differences in endogenous plasma ubiquinone concentration. Coenzyme Q10 measurements (quantified by HPLC-UV) of 16 healthy volunteers were done during the daytime hours of activity beginning at 09:00h one day and ending at 09:00h the next day (13 different determinations) in two distinct months, April and October, of the year. A statistically significant circadian rhythm in plasma ubiquinone concentration that includes only the fundamental 24h component was demonstrated both in the April and October data. Furthermore, the time-point means of the ubiquinone concentration in the October study were invariably higher than those obtained in the April study. No statistically significant differences were found in CoQ10 concentration between male and female subjects, both in April and in October. In addition, racial differences were demonstrated; lower plasma ubiquinone levels were found in Caucasian compared to African subjects. However, the latter small group of subjects failed to demonstrate a circadian rhythm, neither in the April nor in the October analysis.

Cyclosporin effect on noradrenaline release from the sympathetic nervous endings of rat aorta

Arterial hypertension is one of the main side effects of cyclosporin treatment and seems to be due to activation of the sympathetic nervous system. Some authors hypothesized that cyclosporin may act on the sympathetic nervous endings increasing catecholamine release, in agreement with our previous works which demonstrated an increase in rat plasma catecholamine levels after 30 mg/kg per day cyclosporin treatment for 7 weeks. Therefore, the aim of this work was to study the cyclosporin mechanism responsible for that increase in plasma catecholamines. Male Wistar rats were used. Noradrenaline release was performed in vitro experiments after loading rat aorta abdominal segments with 3H-noradrenaline (3H-NA). The release of 3H-NA was measured after electrical stimulation in the presence of 10(-6)M cyclosporin. In another set of experiments electrical stimulation was replaced by a pulse addition of cyclosporin (10(-6)M). Another group of rats was treated with 30 mg/kg per day cyclosporin for 7 weeks and catecholamine contents in aorta abdominal segments and adrenals were measured by high performance liquid chromatography system with electrochemical detection (HPLC-ECD). An increase in the 3H-NA release was observed in both types of in vitro experiments. Since cocaine abolished these cyclosporin effects, the obtained results suggest that cyclosporin may act on the catecholamine transporter across the membrane. In addition, after the 7 weeks of cyclosporin treatment, a significant decrease in catecholamine aorta contents was verified but in adrenals there was no difference regarding to controls. However, the dopamine synthesis/degradation ratio measured by the DA/DOPAC ratio suggests an increase in dopamine synthesis. These facts are in agreement with the enhanced plasma catecholamine levels and with the hypothesis of tissue catecholamine depletion. However, they do not explain the increase in plasma adrenaline levels, since adrenaline is a reflex of adrenal activity. The synthesized dopamine in adrenals seems to be unable to reach vesicles and to be metabolized in adrenaline. The observed decrease in HVA adrenal levels may be a consequence of extraneuronal uptake inhibition or inhibition by cyclosporin of the direct o-methylation of DOPAC. In conclusion, our results suggest that cyclosporin increases catecholamine release from the sympathetic nervous endings by a tyramine-like effect, i.e. by acting directly on the catecholamine transporter of the membrane.

Nitric Oxide Production and Nitric Oxide Synthase Expression in Platelets from Heroin Abusers before and after Ultrarapid Detoxification

Abstract: Prolonged heroin abuse has been associated with neurotoxicity. Thus, the involvement of nitric oxide (NO) in heroin‐induced dopaminergic neurotoxicity could be a reasonable explanation for heroin‐induced changes in brain. Enzymatically derived NO has been implicated in numerous physiological and pathological processes in the brain. Whereas during development NO participates in growing and maturation processes, excess NO production in the adult in response to inflammation, injury, or trauma, participates in both cell death and repair. The expression and activity of the inducible isoform of NO synthase (iNOS) play a pivotal role in sustained and elevated NO release. Recent evidence suggests that neurons can respond to proinflammatory stimuli and take part in brain inflammation. The effect of heroin abuse on platelet NO production and on expression of iNOS in drug addicts submitted to an ultrarapid detoxification was studied. The NO production was estimated from the nitrite concentration, and nitric oxide synthase was determined by Western blotting analysis. Results showed no difference in nitrite content of resting platelets between heroin abuser and control groups. However, after platelet stimulation, heroin abusers showed significantly lower nitrite values. The Western blotting analysis reinforced these results. After ultrarapid detoxification, platelet nitrite production in heroin abusers showed no differences compared to control subjects. Our results suggest that heroin consumption decreases the iNOS synthase expression and platelet NO production. Detoxification treatment restores these changes.

Preserved face inversion effects in adults with autism spectrum disorder: an event-related potential study.

Individuals with autism spectrum disorder (ASD) are impaired in face recognition and emotional expression identification. According to current models, there are at least three levels of face processing: first order (two eyes, above a nose, which is above a mouth), second order (the relative distance between features), and holistic (ability to recognize as faces images that lack distinctive facial features). Some studies have reported deficits in configural and holistic processing in individuals with ASD. We investigated the neural correlates of these phenomena by measuring event-related potentials in high-functioning adults with ASD and healthy controls, during a face decision task, using a comprehensive set of photographic, schematic and Mooney upright and inverted faces, and scrambled images. Behaviorally, ASD and healthy controls were performance matched. At the electrophysiological level, individuals with ASD showed a bilateral N170 inversion effect in latency and left lateralized in amplitude for photographic faces, with bilaterally longer latencies and left higher amplitudes (more negative) N170 for inverted than upright photographic faces, and a right lateralized N170 inversion effect in latency for schematic faces. We conclude that under performance-matched conditions, adults with ASD show preserved N170 inversion effects and associated sparing of facial configural processing. An oral presentation of this work can be consulted using the following link, Supplemental digital content 1, http://links.lww.com/WNR/A382.

TIAPROFENIC ACID-INDUCED PHOTOHEMOLYSIS IN VITRO IS INHIBITED BY NIMESULIDE

The effect of nimesulide on red blood cell (RBC) lysis photosensitized by tiaprofenic acid was investigated. The tiaprofenic acid-induced photohemolysis rate was enhanced by exposure to oxygen but lysis was also observed under anaerobic conditions. Photohemolysis was decreased by reduced glutathione (GSH) and reduced even more by butylated hydroxyanisole (BHA); sodium azide, superoxide dismutase and mannitol did not show a significant effect. Nimesulide did not cause any RBC lysis and inhibited this action of tiaprofenic acid by 20-30%, depending on the concentration of nimesulide and the intensity of ultraviolet A light. The protective effect of GSH, but not of BHA, was increased by nimesulide. Our findings suggest that free radicals are generated in this in vitro model of phototoxicity and are involved in the photoaggression to the red blood cell membrane, this effect being partially inhibited by nimesulide.

Stimulus dependent neural oscillatory patterns show reliable statistical identification of autism spectrum disorder in a face perceptual decision task

OBJECTIVE Electroencephalographic biomarkers have been widely investigated in autism, in the search for diagnostic, prognostic and therapeutic outcome measures. Here we took advantage of the information available in temporal oscillatory patterns evoked by simple perceptual decisions to investigate whether stimulus dependent oscillatory signatures can be used as potential biomarkers in autism spectrum disorder (ASD). METHODS We studied an extensive set of stimuli (9 categories of faces) and performed data driven classification (Support vector machine, SVM) of ASD vs. Controls with features based on the EEG power responses. We carried out an extensive time-frequency and synchrony analysis of distinct face categories requiring different processing mechanisms in terms of non-holistic vs. holistic processing. RESULTS We found that the neuronal oscillatory responses of low gamma frequency band, locked to photographic and abstract two-tone (Mooney) face stimulus presentation are decreased in ASD vs. the control group. We also found decreased time-frequency (TF) responses in the beta band in ASD after 350 ms, possibly related to motor preparation. On the other hand, synchrony in the 30-45 Hz band showed a distinct spatial pattern in ASD. These power changes enabled accurate classification of ASD with an SVM approach. SVM accuracy was approximately 85%. ROC curves showed about 94% AUC (area under the curve). Combination of Mooney and Photographic face stimuli evoked features enabled a better separation between groups, reaching an AUC of 98.6%. CONCLUSION We identified a relative decrease in EEG responses to face stimuli in ASD in the beta (15-30 Hz; >350 ms) and gamma (30-45 Hz; 55-80 Hz; 50-350 ms) frequency ranges. These can be used as input of a machine learning approach to separate between groups with high accuracy. SIGNIFICANCE Future studies can use EEG time-frequency patterns evoked by particular types of faces as a diagnostic biomarker and potentially as outcome measures in therapeutic trials.