RESUMO
Padma 28 is a mixture of herbs used in traditional Tibetan medicine with anti-inflammatory activities. We investigated the effects of Padma 28 on nitric oxide (NO) production by the inducible nitric oxide synthase (iNOS) in lipopolysaccharide stimulated mouse macrophages (RAW 264.7). Padma 28 (0-900 microg/mL) induced a concentration dependent inhibition of inducible nitric oxide synthesis. iNOS protein expression showed a concentration dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of Padma 28. Padma 28 decreased iNOS mRNA levels as shown by RT-PCR. Aqueous extracts from costi amari radix (costus root, the dried root of Saussurea lappa) and the outer cover of myrobalani fructus (the dried fruit of Terminalia chebula), constituents of the complex herb preparation Padma 28, were found to inhibit inducible nitric oxide synthesis by decreasing iNOS protein and iNOS mRNA levels. The inhibition of inducible nitric oxide synthesis might contribute to the anti-inflammatory activities of Padma 28.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Extratos Vegetais/farmacologia , Animais , Arginina/metabolismo , Linhagem Celular , Relação Dose-Resposta a Droga , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/análise , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo II , RNA Mensageiro/análiseRESUMO
Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.
Assuntos
Altitude , Encéfalo/fisiologia , Circulação Cerebrovascular , Hipóxia/fisiopatologia , Adulto , Mapeamento Encefálico , Dióxido de Carbono/sangue , Cerebelo/irrigação sanguínea , Feminino , Humanos , Hipotálamo/irrigação sanguínea , Masculino , Análise Multivariada , Especificidade de Órgãos , Oxigênio/sangue , Pressão Parcial , Tálamo/irrigação sanguíneaRESUMO
We report on two girls, 3 and 13 years old, with acute promyelocytic leukemia (APL) who were successfully treated with all-trans retinoic acid (ATRA) 45 mg/m2/day. "Retinoic acid syndrome" was prevented with short-time treatment of high dose (4 x 1.5 g/m2) cytarabine. This regimen was well tolerated, although both children were critically ill. They achieved a complete remission confirmed by light microscopy, but reverse transcriptase polymerase chain reaction remained positive after ATRA, underlining the need of further chemotherapy.