Hypoactivity of the central dopaminergic system and autistic-like behavior induced by a single early prenatal exposure to lipopolysaccharide

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

Effects of the application of α1- and α2-adrenoceptor agonists and antagonists into the ventromedial hypothalamus on the sodium and potassium renal excretion

The effects of sodium and potassium excretion after intrahypothalamic administration of two α-adrenoceptor agonists and the effect of α-adrenoceptor antagonists were studied in groups of rats. Prazosin was equally effective at blocking the natriuretic and kaliuretic responses to the α1-adrenoceptor agonist phenylephrine and the mixed α1/α2-adrenoceptor agonist noradrenaline, while yohimbine which acts preferentially on α2-adrenoceptors was effective in potentiating these responses. These results suggest the presence of two types of α-adrenoceptors for the modulation of ventromedial hypothalamic pathways that interfere with the regulation of the two cations: stimulation of α1-adrenoceptors facilitates, while stimulation of α2-adrenoceptors inhibits the excretion of the ions.

Effects of the alpha antagonists and agonists injected into the lateral hypothalamus on the water and sodium intake induced by angiotensin II injection into the subfornical organ

The subfornical organ (SFO) and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANG II) on water and salt regulation. Several anatomical findings have demonstrated neural connections between the SFO and the LH. The present experiments were conducted to investigate the role of the α-adrenergic antagonists and agonists injected into the LH on the water and salt intake elicited by injections of ANG II into the SFO. Prazosin (an α1-adrenergic antagonist) injected into the LH increased the salt ingestion, whereas yohimbine (an α2-adrenergic antagonist) and propranolol (a β-adrenergic antagonist) antagonized the salt ingestion induced by administration of ANG II into the SFO. Previous administration of clonidine (an α2-adrenergic agonist) or noradrenaline into the LH increased, whereas pretreatment with phenylephrine decreased the sodium intake induced by injection of ANG II into the SFO. Previous treatment with prazosin and propranolol reduced the water intake induced by ANG II. Phenylephrine increased the dipsogenic responses produced by ANG II, whereas previous treatment with clonidine injected into the LH reduced the water intake induced by ANG II administration into the SFO. The LH involvement with SFO on the excitatory and inhibitory mechanisms related to water and sodium intake is suggested.

Síndrome das pernas inquietas: Diagnóstico e tratamento. Opinião de especialistas Brasileiros

This article contains the conclusions of the November 17-18, 2006 meeting of the Brazilian Study Group of Restless Legs Syndrome (GBE-SPI) about diagnosis and management of restless legs syndrome (RLS). RLS is characterized by abnormal sensations mostly but not exclusively in the legs which worsen in the evening and are improved by motion of the affected body part. Its diagnosis is solely based on clinical findings. Therapeutic agents with efficacy supported by Class I studies are dopamine agonists, levodopa and gabapentine. Class II studies support the use of slow release valproic acid, clonazepan and oxycodone. The GBE-SPI recommendations for management of SPI are sleep hygiene, withdrawal of medications capable of worsening the condition, treatment of comorbidities and pharmacological agents. The first choice agents are dopaminergic drugs, second choice are gabapentine or oxycodone, and the third choice are clonazepan or slow release valproic acid.

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Infertility represents one of the main long-term consequences of combination chemotherapy used for the treatment of breast cancer. Approximately 60%-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ tumors with respect to recurrence-free survival and overall survival, Presentation of the hypothesis: It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. Testing the hypothesis: Assessment of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen. The recurrence-free survival and overall survival should be analysed. Implications of the hypothesis: The major implication will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases. © Todos os direitos reservados a SBRA - Sociedade Brasileira de Reprodução Assistida.

Influence of the dopaminergic system, CREB, and transcription factor-B on cocaine neurotoxicity

Cocaine is a widely used drug and its abuse is associated with physical, psychiatric and social problems. Abnormalities in newborns have been demonstrated to be due to the toxic effects of cocaine during fetal development. The mechanism by which cocaine causes neurological damage is complex and involves interactions of the drug with several neurotransmitter systems, such as the increase of extracellular levels of dopamine and free radicals, and modulation of transcription factors. The aim of this review was to evaluate the importance of the dopaminergic system and the participation of inflammatory signaling in cocaine neurotoxicity. Our study showed that cocaine activates the transcription factors NF-κB and CREB, which regulate genes involved in cellular death. GBR 12909 (an inhibitor of dopamine reuptake), lidocaine (a local anesthetic), and dopamine did not activate NF-κB in the same way as cocaine. However, the attenuation of NF-κB activity after the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, suggests that the activation of NF-κB by cocaine is, at least partially, due to activation of D1 receptors. NF-κB seems to have a protective role in these cells because its inhibition increased cellular death caused by cocaine. The increase in BDNF (brain-derived neurotrophic factor) mRNA can also be related to the protective role of both CREB and NF-κB transcription factors. An understanding of the mechanisms by which cocaine induces cell death in the brain will contribute to the development of new therapies for drug abusers, which can help to slow down the progress of degenerative processes.

Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin

The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP. © 1992.

Efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina, xilazina ou clonidina, em equinos

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

Uso de morfina, xilazina e meloxicam para o controle da dor pós-operatória em cadelas submetidas à ovariossalpingo-histerectomia

Foram realizados estudos empregando-se analgésicos por via epidural e subcutânea em cadelas de diferentes raças e idades, submetidas à castração mediante celiotomia. Vinte animais foram tranquilizados e anestesiados com tiletamina-zolazepam, e aleatoriamente distribuídos em quatro grupos (n=5), de acordo com o fármaco e a via de administração. Os do grupo morfina (GM) foram submetidos à anestesia epidural no espaço lombossacro, com morfina (0,1mg/kg) associada ao cloreto de sódio a 0,9%. Aos do grupo xilazina (GX), foram administrados xilazina (0,2mg/kg) e cloreto de sódio a 0,9%. Os do grupo meloxicam (GME) receberam 0,2mg/kg do anti-inflamatório meloxicam associado ao cloreto de sódio a 0,9%, injetado pela via subcutânea. Os do grupo-controle (CG) receberam apenas cloreto de sódio a 0,9%. O volume final para as injeções epidurais foi padronizado para 0,3mL/kg. A mensuração inicial da concentração de cortisol plasmático, do ritmo cardíaco, da frequência respiratória e os parâmetros comportamentais foram registrados imediatamente antes do procedimento cirúrgico (M1). Registros adicionais foram apresentados às 2, 6, 12 e 24 horas após o procedimento cirúrgico (M2, M3, M4 e M5, respectivamente). As variáveis comportamentais foram avaliadas por meio de sinais clínicos e seus respectivos escores. em GX foram observadas depressão respiratória, bradicardia e concentração de cortisol mais alta do que o registrado no GM. A analgesia obtida pelo meloxicam foi considerada ineficiente. É possível concluir que a morfina, via epidural, promoveu menor incidência de efeitos colaterais e melhor analgesia e bem-estar animal.

Efeito da dexmedetomidina sobre a arritmia cardíaca induzida pela adrenalina em cães anestesiados pelo sevofluorano

Avaliou-se o efeito da dexmedetomidina sobre o ritmo cardíaco em 20 cães, sem raça definida, de ambos os sexos e considerados sadios, anestesiados pelo sevofluorano e submetidos a doses crescentes de adrenalina. Os animais foram, aleatoriamente, distribuídos em dois grupos (placebo e dexmedetomidina). No grupo placebo, os animais receberam, por via intravenosa, solução de NaCl a 0,9%, na dose de 0,3ml/kg. Foram considerados dois momentos, M0 e M1, imediatamente antes e após a aplicação, respectivamente. Após 10 minutos, realizou-se a indução anestésica com sevofluorano, por meio de máscara facial vedada, até a perda do reflexo laringotraqueal. em seguida, procedeu-se à intubação orotraqueal e a manutenção da anestesia foi realizada com a administração de sevofluorano na concentração de 1,5CAM, em circuito anestésico com reinalação parcial de gases. Decorridos 20 minutos da indução anestésica, iniciou-se a administração intravenosa contínua de solução de adrenalina a 2% em doses crescentes de 1, 2, 3, 4 e 5mg/kg/min, por meio de bomba de infusão, com aumento da dose em intervalos de 10 minutos. Imediatamente antes desse acréscimo eram feitas as mensurações (M2 a M6). No grupo dexmedetomidina empregou-se a mesma metodologia substituindo-se a solução de NaCl a 0,9% por hidrocloridrato de dexmedetomidina, na dose de 1µg/kg. Foram registradas as pressões arteriais, em M0 e em M2 a M6, e o traçado eletrocardiográfico, na derivação DII (M2 a M6), considerando-se para efeito estatístico o número total de bloqueios atrioventriculares (BAV) de primeiro e segundo graus e de complexos ventriculares prematuros (ESV), coincidentes com cada dose de adrenalina. Os dados foram submetidos à análise de variância seguida pelo teste de Tukey (P<0,05). Verificou-se que a dexmedetomidina interfere significativamente na condução atrioventricular levando a maior ocorrência de BAV e reduz o número de ESV nas doses infundidas de 2 e 3mg/kg/min de adrenalina. Logo após a aplicação de dexmedetomidina, observaram-se redução da freqüência cardíaca e da pressão arterial, cuja diminuição persistiu por até uma hora.

The improvement of the anti-hyperalgesic effect of ketamine and of its isomers by the administration of ifenprodil

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Incontinência urinária após gonadectomia em fêmeas caninas

A incontinência urinária adquirida é uma condição debilitante e, muitas vezes, incurável que acomete fêmeas castradas e raramente fêmeas inteiras ou machos. A manifestação clínica pode ocorrer em qualquer momento após a gonadectomia e resulta em graves problemas no manejo do paciente. Os mecanismos que desencadeiam a incontinência após ovariectomia envolvem decréscimo na pressão de fechamento uretral, alterações hormonais, aumento na deposição de colágeno na musculatura lisa da bexiga, diminuição na contratilidade do músculo detrusor e redução na resposta aos estímulos elétricos e ao carbachol. O diagnóstico é realizado pelo histórico do animal, pelo exame físico, pelos exames laboratoriais, pelo perfil de pressão uretral, pela ultrassonografia e pelas radiografias abdominais. O tratamento clínico envolve utilização de fármacos -adrenérgicos, estrógenos, análogos de GnRH e agentes antidepressivos. As técnicas cirúrgicas recomendadas correspondem à uretropexia, cistouretropexia, aplicação de colágeno na uretra e colpossuspensão. Melhor compreensão da etiologia, da fisiopatologia, dos métodos de diagnóstico e tratamentos é fundamental em razão do pouco conhecimento e da identificação dessa condição no Brasil.