The effect of unpredictable chronic mild stress on depressive-like behavior and on hippocampal A1 and striatal A2A adenosine receptors.

This study examined the effects of two chronic stress regimens upon depressive-like behavior, A(1) and A(2A) adenosine receptor binding and immunocontent. Male rats were subjected to unpredictable chronic mild stress (UCMS) or to chronic restraint stress (CRS) for 40 days. Subsequently, depressive-like behaviors (forced swimming and consumption of sucrose) were evaluated, and A(1) adenosine or A(2A) adenosine receptors were examined in the hippocampus or striatum, respectively. UCMS animals demonstrated depressive-related behaviors (decrease in sucrose consumption and increased immobility in the forced swimming test). This group also presented increased A(1) adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A(2A) adenosine receptor binding in the striatum, without alteration in immunoreactivity. Conversely, the chronic restraint stress group displayed only an increase in A(1) adenosine receptor binding and no alteration in the other parameters evaluated. We suggest that the alteration in adenosine receptors, particularly the upregulation of striatal A(2A) adenosine receptors following UCMS, could be associated with depressive-related behavior.

Adenosine A1 receptor distribution in the nucleus tractus solitarii of normotensive and spontaneously hypertensive rats.

Adenosine acts at many sites to modulate neuronal activity. The nucleus tractus solitarii (NTS) is a major brain site in cardiovascular control. The present study was undertaken for a detailed analysis of the distribution of A(1) adenosine receptor (A(1)R) in the NTS of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY), using in vitro autoradiography with [(3)H]DPCPX. The density of [(3)H]DPCPX in the whole NTS decreased according to the rostral-caudal levels. This high level of [(3)H]DPCPX binding at rostral sites is due to an specific label of the dorsomedial/dorsolateral subnuclei. On the other hand, analysis of subpostremal subnucleus, showed opposite results. The density of [(3)H]DPCPX binding in the subpostremal NTS increased according to the rostral-caudal levels. Furthermore, it was observed an increased [(3)H]DPCPX binding in the SHR compared with WKY. The results show a complex pattern of A(1)R distribution in the NTS, which highlight the powerful modulatory actions mediated by adenosine in the NTS barosensitive neurons.

CT-2584 (Cell Therapeutics).

CT-2584, an anticancer agent that inhibits phospholipid signaling, is under development by Cell Therapeutics Inc (CTI) as a potential treatment for various types of cancer. Phase II trials are underway for the treatment of prostate cancer and soft-tissue sarcoma [306617], [324290]. According to CIBC World Markets, completion of enrolment for these trials was expected in the fourth quarter of 2000. Furthermore, the initiation of phase II/III trials in combination with taxotere for the treatment of prostate cancer was anticipated in the second half of 2000, as were phase I/II trials in combination with cisplatin for the treatment of other cancers, including lung cancer [396582]. Results of a phase II study in patients with soft-tissue sarcomas evaluating pharmacokinetics, tolerance and therapeutic activity were presented at the 2000 American Society of Clinical Oncology (ASCO) meeting [367283]. Further data are expected to be presented at the ASCO meeting in May 2001 [396582]. Cell Therapeutics is seeking development and commercialization partners for CT-2584 [386398].

Bronquiolite viral aguda - um tema ainda controvertido / Acute viral bronchiolitis - still subject for controversy

Objetivo: Os autores apresentaram uma revisäo sobre bronquiolite viral aguda, salientando os aspectos, ainda controversos, relacionados à terapêutica da doença. Além dessas questöes teóricas, referidas pela literatura, procuram estabelecer um juízo crítico acerca do assunto, referindo suas posiçöes pessoais frente ao manejo dessa doença. Métodos: Foram selecionados, a partir de uma pesquisa no banco de dados da Medline, os artigos que julgamos mais significativos acerca do tema, publicados na literatura médica nos últimos 20 anos. Resultados: Bronquiolite viral aguda é a doença infecciosa do trato respiratório inferior mais freqüêente no primeiro ano de idade. Apesar da sua significativa prevalência e de todo o risco que tal situaçäo porde conferir aos pacientes nessa faixa etária, muito pouco evoluímos acerca da terapêutica empregada nessa situaçäo clínica. Cada vez mais encontramos fundamentada a importância de uma hidrataçäo adequada, dos cuidados necessários para prevenir infecçäo cruzada e da importância da oxigenoterapia. Muitas dúvidas persistem com relaçäo ao papel das drogas broncodilatadoras e antivirais (ribavirina). Alguma perspectivas se abrem com o emprego de imunoglobulinas específicas, principalmente na prevençäo da doença pelo vírus sincicial respiratório em populaçöes de risco. Cada vez menos, encontramos justificada, a utilizaçäo de corticosteróides na fase aguda da doença. Conclusöes: bronquiolite viral aguda é uma doença que ainda carece de tratamento ideal. As rotinas por nós empregadas pouco mudaram nos últimos 30 anos, o que faz com que haja muita controvérsia, acerca da terapêutica a ser utilizada entre os mais diversos centros de assistência.

Pharmacokinetics of enprofylline administered intravenously and as a sustained-release tablet at steady state in children with asthma.

The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained-release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval.