Syndrome inflammatoire chez les schizophrènes toxicomanes

La schizophrénie est une maladie mentale grave qui présente une comorbidité fréquente avec la toxicomanie et avec divers troubles immunitaires. Une méta-analyse réalisée récemment dans notre laboratoire a montré une augmentation d’IL-6 (une cytokine pro-inflammatoire), du récepteur soluble d’IL-2 (un marqueur d’activation du système immunitaire), et d’IL-1RA (une cytokine anti-inflammatoire) dans la schizophrénie, suggérant l’existence d’un syndrome inflammatoire dans cette maladie. La toxicomanie aussi est associée au dérèglement du réseau des cytokines inflammatoires, mais les effets dépendent du type de drogues et ils sont parfois diamétralement opposés. On dispose encore de peu d’informations sur le statut immunitaire et inflammatoire des patients qui ont un double diagnostic de schizophrénie et de toxicomanie. Le but de ce travail était d’explorer l’existence d’un état inflammatoire systémique chez les patients schizophrènes et toxicomanes, et l’influence du traitement avec un médicament antipsychotique atypique, la quétiapine. Les objectifs spécifiques étaient : 1) Mesurer les concentrations plasmatiques des cytokines inflammatoires chez les schizophrènes et toxicomanes avant, pendant et après traitement avec la quétiapine ; et 2) Faire des études de corrélations entre les taux de cytokines, les symptômes cliniques, et la consommation de drogues. Les résultats montrent que comparativement aux contrôles normaux, les patients avec un double diagnostic présentent une augmentation d’IL-6, d’IL-1RA, du sIL-2R et d’IL-8 avant traitement à la quétiapine. Les augmentations des concentrations plasmatiques d’IL-1RA sont particulièrement importantes chez les patients avec double diagnostic, si on les compare à celles publiées chez les schizophrènes sans toxicomanie. Le traitement à la quétiapine n’influence pas les concentrations plasmatiques de ces cytokines, sauf sIL-2R qui augmente davantage au cours du traitement. Des corrélations positives de puissance modérée sont retrouvées entre IL-6 et dépression, IL-6 et alcool, IL-1RA et cognition, IL-8 et dépression, IL-8 et alcool, sIL-2R et cannabis. Notre étude révèle que la réponse inflammatoire est activée chez les schizophrènes et toxicomanes. De plus, la toxicomanie semble jouer un rôle facilitant ou potentialisateur dans les augmentations des taux circulants d’IL-1RA. Les études en cours sur différentes populations de schizophrènes avec ou sans toxicomanie, et chez des toxicomanes non schizophrènes permettront de préciser le rôle des différentes drogues d’abus dans le syndrome inflammatoire chez les schizophrènes, ainsi que les implications de ce syndrome sur le plan clinique et thérapeutique.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Recognition, assessment and treatment of social anxiety disorder: summary of NICE guidance

Social anxiety disorder is one of the most persistent and common of the anxiety disorders, with lifetime prevalence rates in Europe of 6.7% (range 3.9-13.7%).1 It often coexists with depression, substance use disorder, generalised anxiety disorder, panic disorder, and post-traumatic stress disorder.2 It can severely impair a person’s daily functioning by impeding the formation of relationships, reducing quality of life, and negatively affecting performance at work or school. Despite this, and the fact that effective treatments exist, only about half of people with this condition seek treatment, many after waiting 10-15 years.3 Although about 40% of those who develop the condition in childhood or adolescence recover before adulthood,4 for many the disorder persists into adulthood, with the chance of spontaneous recovery then limited compared with other mental health problems. This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on recognising, assessing, and treating social anxiety disorder in children, young people, and adults.5

Morphine treatment during pregnancy modulates behavioral selection in lactating rats

Previous studies have demonstrated that treatment of postpartum female rats with morphine inhibits maternal behavior and stimulates foraging. Exposure to drugs of abuse may result in a progressive enhancement of their reinforcing effects. Puerperal treatment with morphine leads to reverse tolerance to this drug. The present study investigated whether repeated morphine treatment during late pregnancy may influence the effects of different morphine dosages on behavioral selection in lactating rats. Females were simultaneously exposed to pups and insects, and the choice between taking care of the pups and hunting insects was observed. Female Wistar rats were treated with morphine (3.5 mg/kg/day, subcutaneous [s.c.]) or saline for 5 days beginning on pregnancy day 17. On day 5 of lactation, animals were acutely challenged with morphine (0.5, 1.0, or 1.5 mg/kg, s.c.; MM0.5, MM1.0, and MM1.5 groups, respectively) or saline (MS group) and tested for predatory hunting and maternal behavior. Control groups were pretreated with saline and challenged with morphine (SM0.5, SM1.0, and SM1.5 groups) or saline (SS group). Animals treated with morphine during late pregnancy and acutely challenged with 1.0 mg/kg morphine (MM1.0 group) exhibited significantly decreased maternal behavior and enhanced hunting. This effect was not evident with the 0.5 mg/kg dose. The 1.5 mg/kg morphine dose decreased maternal behavior and increased hunting in both the MM1.5 group and in animals challenged with morphine after previous saline treatment (SM1.5 group). These results provide evidence of plasticity of the opioidergic role in behavioral selection during lactation. (C) 2010 Elsevier Inc. All rights reserved.

Seroprevalence of Human Herpesvirus 8 Infection in Individuals From Health Care Centers in Mozambique: Potential for Endemic and Epidemic Kaposi`s Sarcoma

Human herpesvirus 8 (HHV-8) infection is common in sub-Saharan Africa, but its prevalence in Mozambique is unknown. The seroprevalence of HHV-8 in a cohort of individuals seen at public health centers in Northern (n = 208), Central (n = 226), or Southern (n = 318) Mozambique was examined. All individuals were interviewed to obtain socioeconomic, demographic and clinical data and were tested for serum anti-HHV-8 antibodies using an immunofluorescence assay. The overall frequency of HHV-8 antibodies was 21.4% and, in spite of the diversity of epidemiological characteristics of the tested individuals, did not differ significantly among regions: 18.7%, 24.3% and 21.4% in the North, Center, and South, respectively (chi(2), 2.37; P = 0.305). The variables that were associated significantly with the presence of HHV-8 antibodies were gender, age, level of education, number of siblings and HIV serostatus, but these differed across the regions. In the North, although tested individuals lived under poor socioeconomic conditions, no association between HHV-8 infection and household variables was detected, with the exception of the number of siblings (P = 0.042). In the Central region, HHV-8 infection was associated with gender (P = 0.010), the number of household members (P = 0.031), and the place of attendance (P = 0.021). In the South, HHV-8 infection was associated with the number of siblings (P = 0.023) and HIV status (P = 0.002). The overall prevalence of HHV-8 seropositivity increased with age. These results demonstrate that Mozambique is another country in Africa with endemic HHV-8 infection, and, because of the AIDS epidemic, continued access to antiretroviral treatment is necessary to avert an outbreak of AIDS-Kaposi`s sarcoma. J. Med. Virol. 82:1216-1223, 2010. (C) 2010 Wiley-Liss, Inc.

Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice

Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly, the 5-HT(1B) mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT(1B) receptor in the observed behavioral disinhibition.

Ablation of primary afferent neurons by neonatal capsaicin treatment reduces the susceptibility of the portal hypertensive gastric mucosa to ethanol-induced injury in cirrhotic rats

Primary sensory afferent neurons modulate the hyperdynamic circulation in Cirrhotic rats with portal hypertension.The stomach of cirrhotic rats is prone to damage induced by ethanol, a phenomenon associated with reduced gastric hyperemic response to acid-back diffusion. The aim of this study was to examine the impact of ablation of capsaicin-sensitive neurons and the tachykinin NK(1) receptor antagonist A5330 on the susceptibility of the portal hypertensive gastric mucosa, to ethanol-induced injury and its effects on gastric cyclooxygenase (COX) and nitric oxide synthase (NOS) mRNA expression. Capsaicin was administered to neonatal, male, Wistar rats and the animals were allowed to grow. Cirrhosis was then induced by bile duct ligation in adult rats while controls had sham operation. Ethanol-induced gastric damage was assessed using ex vivo gastric chamber experiments. Gastric blood flow was measured as well as COX/NOS mRNA expression. Topical application of ethanol produced significant gastric damage in cirrhotic rats compared to controls, which was reversed in capsaicin- and A5330-treated animals. Mean arterial and portal pressure was normalized in capsaicin-treated cirrhotic rats. Capsaicin and A5330 administration restored gastric blood flow responses to topical application of ethanol followed by acid in cirrhotic rats. Differential COX and NOS mRNA expression was noted in bile duct ligated rats relative to controls. Capsaicin treatment significantly modified gastric eNOS/iNOS/COX-2 mRNA expression in cirrhotic rats. Capsaicin-sensitive neurons modulate the susceptibility of the portal hypertensive gastric mucosa to injury induced by ethanol via tachykinin NK(1) receptors and signalling of prostaglandin and NO production/release. (c) 2008 Elsevier B.V. All rights reserved.

TL dosimetry of natural quartz sensitized by heat-treatment and high dose irradiation

The aim of this paper is to report the sensitization of the TL peak appearing at 270 degrees C in the glow curve of natural quartz by using the combined effect of heat-treatments and irradiation with high gamma doses. For this, thirty discs with 6 x 1 mm(2) were prepared from plates parallell to a rhombolledral crystal face. The specimens were separated into four lots according to its TL read out between 160 and 320 degrees C. One lot was submitted to gamma doses of Co-60 radiation starting at 2 kGy and going up until a cumulative dose of 25 kGy. The other three lots were initially heal-treated at 500, 800 and 1000 degrees C and then irradiated with a single dose of 25kGy. The TL response of each lot was determined as a function of test-doses ranging from 0.1 to 30 mGy. As a result, it was observed that heat-treatments themselves did not produce the strong peak at 270 degrees C that was observed after the administration of high gamma doses. This peak is associated with the optical absorption band appearing at 470 rim which is due to the formation of [AlO4]degrees acting as electron-hole recombination centers. The formation of the 270 degrees C peak was preliminary analyzed in relation to aluminum- and oxygen-vacancy-related centers found in crystalline quartz. (C) 2008 Elsevier Ltd. All rights reserved.

Alcohol use disorders in patients with obsessive-compulsive disorder: The importance of appropriate dual-diagnosis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Mucosal Bridge of the Vocal Fold: Difficulties in the Diagnosis and Treatment

Mucosal bridges are rare laryngeal lesions probably of genetic origin. They may cause dysphonia of varying degrees, especially when associated with other laryngeal lesions such as vocal sulci and cysts. Reports on mucosal bridges are rare, and the better treatment is inconclusive.Aim. To report the authors' experience in 14 cases of mucosal bridge showing details on endoscopic examinations and treatment.Study Design. Retrospective study.Methods. We reviewed the medical records of 14 patients with a diagnosis of mucosal bridge confirmed by video-laryngostroboscopy and direct laryngoscopy who attended the Outpatient Clinic of Voice Disorders of the Discipline of Otorhinolaryngology, Botucatu Medical School, São Paulo State University, São Paulo. Data collected included information on gender, age, symptoms, time of onset, history of intubation, smoking status, alcohol intake, associated laryngeal lesions, treatment, and GRBAS (grade of hoarseness, roughness, breathiness, asthenia, and stress) scale ratings.Results. of 14 patients, 10 were females and four were males. There was a prevalence of adults (n = 12), with only two of the patients being younger than 13 years (10 and 13 years). Mucosal bridges showed no correlations with smoking, alcohol intake, or gastroesophageal and sinonasal symptoms. Voice abuse was reported in 50% of the cases that consisted of patients who had high-voice demand occupations. In seven cases, mucosal bridges were associated with other laryngeal lesions, particularly vocal cysts and sulci. All patients who underwent surgery and phonotherapy showed improved vocal quality.Conclusions. We documented 14 patients with dysphonia caused by mucosal bridge. Promising results were obtained with surgery.

Effect of root surface treatment with propolis and fluoride in delayed tooth replantation in rats

Replantation is an acceptable option for treatment of an avulsed permanent tooth. Nevertheless, an extended extraoral period damages the periodontal ligament and results in external root resorption. The purpose of this study was to assess by histologic and histometric analysis, the influence of propolis 15% (natural resinous substance collected by Apis mellifera bees from various plants) and the fluoride solution used as root surface treatment on the healing process after delayed tooth replantation. Thirty Wistar (Rattus norvegicus albinus) rats were submitted to extraction of their upper right incisor. The teeth were maintained in a dry environment for 60 min. After this, the pulp was extirpated and the papilla, enamel organ and periodontal ligament were removed with scalpel. The teeth were divided into three experimental groups: Group I - teeth immersed in 20 ml of physiologic saline; Group II - teeth immersed in 20 ml of 2% acidulated phosphate sodium fluoride; Group III - teeth immersed in 20 ml of 15% propolis. After 10 min of immersion in the solutions, the root canals were dried and filled with calcium hydroxide paste and the teeth were replanted. The animals were euthanized 60 days after replantation. The results showed that similar external root resorption was seen in the propolis and fluoride groups. Teeth treated with physiologic saline tended to have more inflammatory root resorption compared with those treated with fluoride or propolis. However, the comparative analysis did not reveal statistically significant differences (P > 0.05) between the treatment modalities when used for delayed tooth replantation.

Thermal behavior of residues (sludge) originated from Araraquara water and sewage treatment station

The number of the cities with canalized water and sewage treatment stations has increased lately and consequently having in mind the great concern on environment preservation and the quality of the water used by society. However, these stations are nowadays causing another kind of problem: a huge quantity of sludge as residue. Due to the implication of the residue on the environment and, consequently, to human life quality, performing of an accurate investigation about the components of such sludge, as well as the thermal stability of this residue in the environment become necessary. This paper presents a study on sludge from water and sewage treatment station, as well as the thermal characterization of residue. Such study was performed through FTIR, atomic absorption, thermoanalytical (TG/DTG, DTA) techniques, that made it possible to observe that the main components of the sludge are clay, carbonates and organic substance, presenting a low rate of metals and a unique thermal behavior since the sludge from the treatment station has a higher thermal stability.

Effects of diethylpropion treatment and withdrawal on aorta reactivity, endothelial factors and rat behavior

Diethylpropion (DEP) is an amphetamine-like compound used as a coadjutant in the treatment of obesity and which presents toxicological importance as a drug of abuse. This drug causes important behavioral and cardiovascular complications; however, the vascular and behavioral alterations during DEP treatment and withdrawal, have not been determined. We evaluated the effects of DEP treatment and withdrawal on the rat aorta reactivity to noradrenaline, focusing on the endothelium, and the rat behavior during DEP treatment and withdrawal. DEP treatment caused a hyporreactivity to noradrenaline in aorta, reversible after 2 days of withdrawal and abolished by both the endothelium removal and the presence of L-NAME, but not by the presence of indomethacin. Furthermore, DEP treatment increased the general activity of rats. Contrarily, DEP withdrawal caused a decrease in the locomotor activity and an increase in grooming behavior, on the 2nd and 7th days after the interruption of the treatment, respectively. DEP treatment also caused an adaptive vascular response to noradrenaline that seems to be dependent on the increase in the endothelial nitric oxide system activity, but independent of prostaglandins synthesis. The data evidenced chronological differences in the adaptive responses of the vascular and central nervous systems induced by DEP treatment. Finally, a reversion of the adaptive response to DEP was observed in the vascular system during withdrawal, whereas a neuroadaptive process was still present in the central nervous system post-DEP. These findings advance on the understanding of the vascular and behavioral pathophysiological processes involved in the therapeutic and abusive uses of DEP. (C) 2003 Elsevier B.V. (USA). All rights reserved.

An open-label, comparative study of the efficacy and safety of once-daily dose of enoxaparin versus unfractionated heparin in the treatment of proximal lower limb deep-vein thrombosis

Background: Treatment of deep-vein thrombosis (DVT) with a once-daily regimen of enoxaparin, rather than a continuous infusion of unfractionated heparin (UFH) is more convenient and allows for home care in some patients. This study was designed to compare the efficacy and safety of these two regimens for the treatment of patients with proximal lower limb DVT. Methods: 201 patients with proximal lower limb DVT from 13 centers in Brazil were randomized in an open manner to receive either enoxaparin [1.5 mg/kg subcutaneous (s.c.) OD] or intravenous (i.v.) UFH (adjusted to aPTT 1.5-2.5 times control) for 5-10 days. All patients also received warfarin (INR 2-3) for at least 3 months. The primary efficacy endpoint Was recurrent DVT (confirmed by venography or ultrasonography), and safety endpoints included bleeding and serious adverse events. The rate of pulmonary embolism (PE) was also collected. Hospitalization was at the physician's discretion. Results: Baseline patient characteristics were comparable between groups. The duration of hospital stay was significantly shorter with enoxaparin than with UFH (3 versus 7 days). In addition, 36% of patients receiving enoxaparin did not need to be hospitalized, whereas all of the patients receiving UFH were! hospitalized. The treatment duration was slightly longer with enoxaparin (8 versus 7 days). There was a nonsignificant trend toward a reduction in the rate of recurrent DVT with enoxaparin versus UFH, and similar safety. Conclusions: A once-daily regimen of enoxaparin 1.5 mg/kg subcutaneous is at least as effective and safe as conventional treatment with a continuous intravenous infusion of UFH. However, the once daily enoxaparin regimen is easier to administer (subcutaneous versus intravenous), does not require aPTT monitoring, and leads to both a reduced number of hospital admissions and an average 4-day-shorter hospital stay. (C) 2004 Elsevier Ltd. All rights reserved.

Response to Treatment in a Prospective Cohort of Patients with Large Ulcerated Lesions Suspected to Be Buruli Ulcer (Mycobacterium ulcerans Disease)

Background: The World Health Organization (WHO) advises treatment of Mycobacterium ulcerans disease, also called Buruli ulcer'' (BU), with a combination of the antibiotics rifampicin and streptomycin (R+S), whether followed by surgery or not. In endemic areas, a clinical case definition is recommended. We evaluated the effectiveness of this strategy in a series of patients with large ulcers of >= 10 cm in longest diameter in a rural health zone of the Democratic Republic of Congo (DRC).Methods: A cohort of 92 patients with large ulcerated lesions suspected to be BU was enrolled between October 2006 and September 2007 and treated according to WHO recommendations. The following microbiologic data were obtained: Ziehl-Neelsen (ZN) stained smear, culture and PCR. Histopathology was performed on a sub-sample. Directly observed treatment with R+S was administered daily for 12 weeks and surgery was performed after 4 weeks. Patients were followed up for two years after treatment.Findings: Out of 92 treated patients, 61 tested positive for M. ulcerans by PCR. PCR negative patients had better clinical improvement than PCR positive patients after 4 weeks of antibiotics (54.8% versus 14.8%). For PCR positive patients, the outcome after 4 weeks of antibiotic treatment was related to the ZN positivity at the start. Deterioration of the ulcers was observed in 87.8% (36/41) of the ZN positive and in 12.2% (5/41) of the ZN negative patients. Deterioration due to paradoxical reaction seemed unlikely. After surgery and an additional 8 weeks of antibiotics, 98.4% of PCR positive patients and 83.3% of PCR negative patients were considered cured. The overall recurrence rate was very low (1.1%).Interpretation: Positive predictive value of the WHO clinical case definition was low. Low relapse rate confirms the efficacy of antibiotics. However, the need for and the best time for surgery for large Buruli ulcers requires clarification. We recommend confirmation by ZN stain at the rural health centers, since surgical intervention without delay may be necessary on the ZN positive cases to avoid progression of the disease. PCR negative patients were most likely not BU cases. Correct diagnosis and specific management of these non-BU ulcers cases are urgently needed.