Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos dos esteroides anabólicos androgênicos sobre funções cognitivas de ratos

The use and the demand for substances that enhance masculinity, strength and sexual power are not novel. Over the years, this search has assisted the research directions in this area, leading to the discovery of the primary male sex hormone testosterone in 1935. Since then, numerous testosterone analogue compounds were synthesized, which are generically called Anabolic Androgenic Steroids (AAS). The AAS were produced for therapeutic purposes, but an increase in the use of these compounds for other purposes occurred over time. Initially they were used mainly to improve performance in athletes. However, recent studies have shown that the use of AAS by non-athletes with aesthetical purposes have been increasing as well. The abuse of AAS with non-clinical purposes can promote a number of physiological alterations, such as heart, liver, respiratory and psychological problems such as changes in mood, levels of anxiety and aggression. Exposure to supraphysiological doses of AAS is associated with behavioral changes, however, little is known about the effects of AAS on cognitive functions. In this work, we aimed to mimic the AAS abuse in humans with intramuscular administration of a supraphysiological dose of testosterone propionate (TP) in rats. We investigated the effects of this treatment on different aspects of cognitive function, specifically learning, memory and anxiety. Adult male Wistar rats were tested in the spontaneous alternation, novel object recognition and plus-maze discriminative avoidance tasks. The control group received intramuscular injections of vegetable oil (vehicle), and the TP group received injections of TP (10 mg/kg, i.m.). The injections were administered for 40 days, with intervals of 48 hours (chronic treatment) or in a single injection (acute treatment). In addition to the behavioral assessments, we performed biochemical analyzes as indicators of the endocrine effects of the treatment. Our results show that chronic treatment with a supraphysiological dose of TP caused memory impairments in the novel object recognition and the discriminative avoidance tasks. The spatial working memory (evaluated by spontaneous alternation task) was not affected. Also, we did not observe changes in anxiety levels. Regarding the biochemical parameters, chronic treatment increased serum levels of glutamicpyruvic transaminase, an indicator of hepatic and pancreatic lesions (as those observed after chronic use of these substances in humans). On the other hand, acute treatment with PT did not promote significant changes in any of these parameters when compared to the control group. In summary, we conclude that chronic treatment with a supraphysiological dose of testosterone propionate produces memory deficits in novel object recognition and retrieval of the discriminative avoidance task in adult male rats

Estudo da preferência manual durante o desenvolvimento ontogenético em sagüi comum ( Callithix jacchus)

The study of manual preference is a widely used approach to investigate cerebral laterality in nonhuman primates. However, in New World primates, little is known about the ontogenesis of hand use asymmetry, in both forced and spontaneous activities, as well as how they correlate with sexual hormones. Accordingly, a longitudinal study was conducted on the manual preference of 6 female and 4 male common marmosets (Callithrix jacchus). The study included the record of forced tests to reach for the food using only one hand (forced activity) and activities such as grooming (auto and social), scratching, grasping the food and hanging, in weekly sessions from the infantile (4 months) to the early adult phase (15 months). Feces samples were also collected, at least once a week, to evaluate the level of gonadal steroids and their influence on these behaviors. In the forced activity, the results confirm the influence of the development period on manual preference during feeding, shown by the increase in lateral stability when grasping the food between the juvenile and adult phases. During this period, a sexual hormone effect on development was also observed, mainly of progesterone in females and androgen in males, but no difference between sexes was found. In the females, progesterone also influenced the manual preference index, with a proportional increase in the degree of manual asymmetry during puberty. With respect to spontaneous activities, the animals showed proportional use of both hands when scratching, hanging, holding the food and grooming. A positive correlation was also found between the preference for holding the food in forced activities and in spontaneous activities

Clinical and Histological Effects of the Intrathecal Administration of Methylprednisolone in Dogs

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Anestesia em paciente obstétrica portadora de anemia falciforme e traço talassêmico após plasmaféresis: relato de caso

JUSTIFICATIVA E OBJETIVOS: A plasmaféresis é a técnica de tratamento de escolha para pacientes com anemia hemolítica grave. Uma de suas conseqüências é a depleção de colinesterase plasmática, o que interfere na metabolização de alguns bloqueadores neuromusculares de uso corrente na prática anestesiológica. RELATO do CASO: Paciente com 26 anos, estado físico ASA IV, gestação de 30 semanas e 3 dias, portadora de anemia falciforme, traço talassêmico e alo-imunização para antígenos de alta freqüência. Apresentou crise de falcização, sendo transfundida com derivado sangüíneo incompatível. Evoluiu com hemólise maciça, sendo admitida com hemoglobina de 3 g/dL e hematócrito de 10%, icterícia intensa, taquicardia, apatia e descoramento. Na avaliação hematológica concluiu-se ser situação de inexistência de sangue compatível para transfusão. Foi tratada com corticoterapia, imunoglobulinas e plasmaféresis. No segundo dia de internação, evoluiu com insuficiência renal aguda e edema pulmonar agudo, piora do estado geral e instabilidade hemodinâmica. Indicada a resolução da gestação em decorrência do quadro clínico da paciente e do sofrimento fetal agudo que se sobrepôs. A paciente foi admitida na sala de operações consciente, dispnéica, pálida, ictérica, SpO2 de 91% em ar ambiente, freqüência cardíaca de 110 bpm e pressão arterial de 110 x 70 mmHg, em uso de dopamina (1 µg.kg-1.min-1) e dobutamina (10 µg.kg-1.min-1). Optou-se por anestesia geral balanceada, com alfentanil (2,5 mg), etomidato (14 mg) e atracúrio (35 mg) e isoflurano. Não se observou intercorrências anestésico-cirúrgicas. Ao final, a paciente foi encaminhada à UTI, sob intubação orotraqueal, e em uso de drogas vasoativas, tendo sido extubada após 3 horas. CONCLUSÕES: Este caso mostrou-se um desafio para a equipe, visto que a paciente apresentava instabilidade hemodinâmica e alteração do coagulograma, condições que contra-indicam a anestesia regional; além disto, a plasmaféresis potencialmente depleta os estoques de colinesterases plasmáticas, o que interfere na anestesia. Entretanto, o arsenal medicamentoso disponível permitiu o manuseio seguro desta situação.

Lupus eritematoso sistêmico: novo fator de risco para aterosclerose?

OBJETIVO: Avaliar a prevalência de eventos cardiovasculares (ECV) secundários à aterosclerose em pacientes com lupus eritematoso sistêmico (LES) e correlacioná-los aos tradicionais fatores de risco, tempo de doença e drogas utilizadas na terapia. MÉTODOS: Estudo retrospectivo através da coleta e análise dos dados contidos nos prontuários de pacientes com diagnóstico confirmado há no mínimo dois anos e seguidos desde 1992. Foram considerados ECV: angina do peito (AP), IAM e acidente vascular cerebral (AVC) de causa não relacionada à atividade do LES. Foram computados os fatores de risco para aterosclerose e dados sobre tratamento. RESULTADOS: Foram analisados 71 prontuários. A média de idade dos pacientes foi de 34,2±12,7 anos; 68 mulheres e três homens; 58 caucasóides (81,6%). Dez (14,08%) apresentaram ECV. Os pacientes nos quais os eventos cardiovasculares foram observados apresentavam idade mais elevada (42,7 vs 32,8 anos p=0,0021) e maior tempo de doença (10,8 vs 7,2 anos p=0,011). Os tradicionais fatores de risco, as doses diárias e cumulativas de esteróides, imunossupressores e antimaláricos não apresentaram diferença estatística significante entre pacientes que apresentaram ou não ECV. CONCLUSÃO: A prevalência de secundários à aterosclerose no LES foi semelhante ao da literatura, 14,08%. Os tradicionais fatores de risco não mostraram associação com a ocorrência ou não de ECV no LES. Os pacientes nos quais os eventos cardiovasculares foram observados apresentavam idade mais elevada e maior tempo de doença. É precoce estabelecer-se que o LES possa ser um fator independente no desenvolvimento da aterosclerose.

Efeito da oferta dietética de proteína sobre o ganho muscular, balanço nitrogenado e cinética da 15N-glicina de atletas em treinamento de musculação

The effect of increased protein intake on the muscle mass gain, nitrogen balance and N-15-glycine kinetics was studied in six young, healthy subjects practitioners of strength training (> 2 years), without use of anabolic steroids and in agreement with the ethical principles of the research. All athletes received adequate diet (0.88g protein/kg/day) during 2 weeks prior the study (D1), and thereafter with diet providing 1.5g of protein/kg/day and 30kcal/g of protein (D2 diet) for the subsequent 2 weeks. Later on, they all received diet with 2.5g of protein/kg/day (D3 diet) and 30 kcal/g protein for the last two weeks. Body composition, food intake, blood biochemistry, nitrogen balance (NB) and 15N-glycine kinetics were determined at the beginning, after D1 (M0) and in the last days of the D2 (M1) and D3 (M2). The results showed at the end of the study (4 weeks) significant increase in muscle mass (1.63 +/- 0.9kg), without difference between D2 and D3. The NB followed the protein/energy consumption (M0 = -7.8g/day; M1 = 5.6g/day and D3 = 16.6g/day), the protein synthesis followed the NB, with M0 < (M1= M2) (M1 = 49.8 +/- 12.2g N/day and M2 = 52.5 +/- 14.0g N/day). Protein catabolism rate was similarly kept among diets. Thus, the results of the NB and N-15-glycine kinetics indicate that the recommended protein intake for these athletes is higher than the one for sedentary adults (0.88g/kg) and lower than 2.5g/kg, around 1.5g of protein/kg/day, with adjustment of the energy consumption to 30 kcal/g of protein.

Recondicionamento muscular na DPOC: principais intervenções e novas tendências

Há algum tempo o condicionamento físico vem sendo parte obrigatória no tratamento de portadores de DPOC. Estes pacientes apresentam comumente intolerância ao exercício de intensidade variável e relacionada à disfunção muscular esquelética. Neste sentido, o exercício físico apresenta-se como ramo mais importante no processo de reabilitação pulmonar. O exercício aeróbio e o treino de força com pesos são fundamentais no incremento de capacidade física e qualidade de vida, principalmente naqueles indivíduos que apresentam as formas moderada ou grave da DPOC. Além disso, espera-se atualmente maior desenvolvimento nas pesquisas em relação à aplicação de estimulação elétrica neuromuscular (EENM) e ao uso criterioso de substâncias ergogênicas tais como esteróides anabolizantes e creatina oral. Tendo em vista as repercussões negativas da disfunção muscular e a importância da reabilitação pulmonar no tratamento da DPOC, esta revisão tem como objetivo reunir informações de estudos relevantes acerca das principais estratégias para o recondicionamento muscular esquelético nestes pacientes nos últimos 15 anos.

Treatment of Acral Persistent Papular Mucinosis with Electrocoagulation

Background: Acral persistent papular mucinosis is a rare localized form of lichen myxedematosus with few case reports and no documented therapeutic options.Objective: To report full resolution of acral persistent papular mucinosis after electrocoagulation.Methods: Case report of a 51-year-old white female diagnosed with an acral persistent papular mucinosis. The clinical and histopathologic features, treatment provided, and response to treatment are detailed.Results: Acral persistent papular mucinosis presented as multiple asymptomatic normochromic papules on the wrists. Treatment with topical and intralesional steroids was unsatisfactory. Gentle electrocoagulation led to complete resolution of the lesions and negligible scarring. The favorable results remained for 6 months of follow-up, and no new lesions have emerged.Conclusion: Our case of acral persistent papular mucinosis was successfully treated with electrocoagulation and long-lasting, excellent cosmetic results.

Risk factors for Hospital-Acquired Pneumonia in nonventilated adults

Although most recent publications focus on Ventilator-associated Pneumonia, Non-Ventilator-associated Hospital-acquired pneumonia (NVHAP) is still worrisome. We studied risk factors for NVHAP among patients admitted to a small teaching hospital. Sixty-six NVHAP case patients and 66 controls admitted to the hospital from November 2005 through November 2006 were enrolled in a case-control study. Variables under investigation included: demographic characteristics, comorbidities, procedures, invasive devices and use of medications (Sedatives, Antacids, Steroids and Antimicrobials). Univariate and multivariable analysis (hierarchical models of logistic regression) were performed. The incidence of NVHAP in our hospital was 0.68% (1.02 per 1,000 patients-day). Results from multivariable analysis identified risk factors for NVHAP: age (Odds Ratio[OR]=1.03, 95% Confidence Interval[CI]=1.01-1.05, p=0.002), use of Antacids (OR=5.29, 95%CI=1.89-4.79, p=0.001) and Central Nervous System disease (OR=3.13, 95%CI=1.24-7.93, p=0.02). Although our findings are coherent with previous reports, the association of Antacids with NVHAP recalls a controversial issue in the physiopathology of Hospital-Acquired Pneumonia, with possible implications for preventive strategies.

Clinical presentation and salivary gland histopathology of paediatric primary Sjogren's syndrome

ObjectiveExplore the presentation, diagnostic criteria and exocrine gland histopathology of paediatric primary Sjogren's syndrome (PPSjS).MethodsA case series of 8 children is reported and American-European Consensus Group (AECG-2002) criteria were examined, as well as minor labial salivary and lachrymal gland biopsies, which were scored by a pathologist blinded to outcome. For all cases, connective tissue diseases and parotid-related infectious disease were excluded.ResultsAge at onset varied from 5-13 years old; 6 were females, all followed from diagnosis up to the last visit (1-10 years). The main features at presentation were recurrent tender parotid swelling and sialectasis imaging, with decreased salivary function assessed by Tc-99 scintigraphy. Mild sicca symptoms were observed in 4/8 cases. Systemic features, including fatigue, myalgia, arthritis, tenosynovitis, joint contractures, transient Raynaud's and high ESR, were recorded at onset. Autoantibody profile was unremarkable for diagnosis, while lymphocytic infiltration of labial salivary glands and sialectasis were observed in all biopsies (8/8). In lachrymal glands, massive lymphocytic infiltration and lymphocytic gastritis were observed during complementary assessment. Flares were treated with low dose steroids and long-term use of hydroxychloroquine (5/8), although only 318 fulfilled AECG-2002 diagnostic criteria, throughout the disease course.ConclusionPPSjS is rare, slowly progressive and its early presentation is variable. Standardised diagnostic algorithms should include recurrent parotid swelling and early diagnosis should rely mostly on salivary and lachrymal gland histopathology in this age group.

A Brazilian registry of juvenile dermatomyositis: onset features and classification of 189 cases

ObjectiveTo describe onset features, classification and treatment of juvenile dermatomyositis (JDM) and juvenile polymyositis (JPM) from a multicentre registry.MethodsInclusion criteria were onset age lower than 18 years and a diagnosis of any idiopathic inflammatory myopathy (IIM) by attending physician. Bohan & Peter (1975) criteria categorisation was established by a scoring algorithm to define JDM and JPM based oil clinical protocol data.ResultsOf the 189 cases included, 178 were classified as JDM, 9 as JPM (19.8: 1) and 2 did not fit the criteria; 6.9% had features of chronic arthritis and connective tissue disease overlap. Diagnosis classification agreement occurred in 66.1%. Medial? onset age was 7 years, median follow-up duration was 3.6 years. Malignancy was described in 2 (1.1%) cases. Muscle weakness occurred in 95.8%; heliotrope rash 83.5%; Gottron plaques 83.1%; 92% had at least one abnormal muscle enzyme result. Muscle biopsy performed in 74.6% was abnormal in 91.5% and electromyogram performed in 39.2% resulted abnormal in 93.2%. Logistic regression analysis was done in 66 cases with all parameters assessed and only aldolase resulted significant, as independent variable for definite JDM (OR=5.4, 95%CI 1.2-24.4, p=0.03). Regarding treatment, 97.9% received steroids; 72% had in addition at least one: methotrexate (75.7%), hydroxychloroquine (64.7%), cyclosporine A (20.6%), IV immunoglobulin (20.6%), azathioprine (10.3%) or cyclophosphamide (9.6%). In this series 24.3% developed calcinosis and mortality rate was 4.2%.ConclusionEvaluation of predefined criteria set for a valid diagnosis indicated aldolase as the most important parameter associated with de, methotrexate combination, was the most indicated treatment.

Factors affecting fertilisation and early embryo quality in single- and superovulated dairy cattle

Data on fertilisation and embryo quality in dairy cattle are presented and the main factors responsible for the low fertility of single-ovulating lactating cows and embryo yield in superovulated dairy cattle are highlighted. During the past 50 years, the fertility in high-producing lactating dairy cattle has decreased as milk production increased. Recent data show conception rates to first service to be approximately 32% in lactating cows, whereas in heifers it has remained above 50%. Fertilisation does not seem to be the principal factor responsible for the low fertility in single-ovulating cows, because it has remained above 80%. Conversely, early embryonic development is impaired in high-producing dairy cows, as observed by most embryonic losses occurring during the first week after fertilisation. However, in superovulated dairy cattle, although fertilisation failure is more pronounced, averaging approximately 45%, the percentage of fertilised embryos viable at 1 week is quite high (>70%). Among the multifactorial causes of low fertility in lactating dairy cows, high feed intake associated with low concentrations of circulating steroids may contribute substantially to reduced embryo quality. Fertilisation failure in superovulated cattle may be a consequence of inappropriate gamete transport due to hormonal imbalances.

Gonadal function arrest in fillies after birth, as reflected by steroid serum concentrations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of neonatal castration and androgenization on sexual dimorphism in bone, leptin and corticosterone secretion

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)