Anti-inflammatory effects of Zingiber officinale roscoe involve suppression of nitric oxide and prostaglandin E2 production

Inflammation is a physiological response to injury and infection. However, chronic inflammation causes tissue damage and is a feature of most chronic diseases. Despite significant progress in developing therapies to target chronic inflammation over the years, almost all current therapies have serious side effects. The current investigation is to identify naturally-existing anti-inflammatory therapies with fewer side effects. The anti-inflammatory effects and mechanisms of action of extracts and fractions obtained using vacuum liquid chromatography [VLC] from ginger [Zingiber officinale] on the production of nitric oxide [NO] and prostaglandin E[2] [PGE[2]] were investigated. NO and PGE[2] production were induced by stimulating the mouse RAW264.7 monocyte/macrophage cell line with lipopolysaccharide [LPS]. Levels of NO and PGE[2] were deter-mined using the Griess method and enzyme linked sorbent assay [ELISA], respectively. Extracts of two Zingiber officinale species obtained with chloroform showed po-tent inhibitory effects on NO and PGE[2] production. The extracts had a higher potency than N[G]-nitro-L-arginine methyl ester [L-NAME], a known specific inducible nitric oxide synthase [iNOS] inhibitor and were comparable in their effects on PGE[2] with Indomethacin, a specific PGE[2] inhibitor. Further, we identified a fraction [F6] that had most potent inhibi-tory effects. The study shows that extract of Zingiber officinale have strong inhibitory effects on key pro-inflammatory mediators involved in chronic inflammation. Both the extracts and F6 had better inhibitory effects than established pharmaceutical inhibitors of NO and PGE[2]

Inibidores das prostaglandinas para profilaxia da patência do canal arterial em recém-nascidos prematuros: revisão sistemática / Prostaglandin inhibitors for prevention of patent ductus arteriosus in preterm infants: a systematic review

A avaliação das tecnologias neonatais assume grande importância em face dapredominância atual do componente neonatal na mortalidade infantil e da necessidade de melhor avaliação dos recursos tecnológicos utilizados na assistência a essa faixa etária. Oestudo teve por objetivo examinar as evidências acerca do uso profilático dosantiinflamatórios não-esteróides – indometacina e ibuprofeno - no fechamento do canal arterial em recém-nascidos prematuros, por intermédio de uma revisão sistemática. Foi executada busca nas bases de referências bibliográficas MEDLINE, Web of Science, Scopus e LILACS, além dos registros da Colaboração Cochrane e da International Network of Agencies for Health Technology Assessment (INAHTA). Foram encontradas 226 citações, dos quais 93 foram para avaliação de resumos. Destes, foram excluídos 68 trabalhos por não preencherem os critérios estabelecidos de inclusão e qualidade, restando 25 artigos para a revisão sistemática, sendo seis envolvendo o uso de ibuprofeno e 19, o de indometacina. O fechamento farmacológico do canal arterial, eleito como desfecho primário,esteve presente em todos os trabalhos incluídos. Outros desfechos estudados foram: fechamento cirúrgico do canal arterial, mortalidade neonatal, doença da membrana hialina, hemorragia intracraniana, sepse neonatal, enterocolite necrosante, tempo de ventilação mecânica invasiva, tempo de oxigenioterapia, tempo de internação hospitalar, pneumotórax, hemorragia pulmonar, hemorragia gastrointestinal, distúrbio de coagulação, creatinina,oligúria, retinopatia da prematuridade, broncodisplasia pulmonar e alterações neurológicas aos 36 meses...

Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

This study was undertaken in anesthetized dogs to evaluate the relative participation of prostaglandins (PGs) and nitric oxide (NO) in the maintenance of total renal blood flow (TRBF), and renal medullary blood flow (RMBF). It was hypothesized that the inhibition of NO should impair cortical and medullary circulation because of the synthesis of this compound in the endothelial cells of these two territories. In contrast, under normal conditions of perfusion pressure PG synthesis is confined to the renal medulla. Hence PG inhibition should predominantly impair the medullary circulation. The initial administration of 25 µM kg-1 min-1 NG-nitro-L-arginine methyl ester produced a significant 26 percent decrease in TRBF and a concomitant 34 percent fall in RMBF, while the subsequent inhibition of PGs with 5 mg/kg meclofenamate further reduced TRBF by 33 percent and RMBF by 89 percent. In contrast, the initial administration of meclofenamate failed to change TRBF, while decreasing RMBF by 49 percent. The subsequent blockade of NO decreased TRBF by 35 percent without further altering RMBF. These results indicate that initial PG synthesis inhibition predominantly alters the medullary circulation, whereas NO inhibition decreases both cortical and medullary flow. This latter change induced by NO renders cortical and RMBF susceptible to a further decrease by PG inhibition. However, the decrease in medullary circulation produced by NO inhibition is not further enhanced by subsequent PG inhibition.

Reactividad vascular pulmonar y formación de edema en presencia de inhibidores de prostaglandinas en el lóbulo canino aislado / Pulmonary vascular reactivity and edema formation in the presence of prostaglandins' inhibitors. Study in isolated canine pulmonary lobule

El propósito de este trabajao es el estudio de la reactividad vascular pulmonar y la formación de edema al acentuar la vasoconstricción arterial pulmonar a la hipoxia mediante un inhibidor de la producción de prostaglandinas: el ácido tiaprofénico. Se utilizó un modelo experimental ex-vivo de lóbulo canino aislado. La formación de edema fue cuantificada utilizando el método de espectrofotometría, previamente publicado por nosotros. Se estudiaron 6 lóbulos caninos, todos bajo dos condiciones: normoxia (FIO2 21 por ciento) e hipoxia (FIO2 5 por ciento); en cuatro de los seis experimentos de iniciaron con el periodo de normoxia y en dos en condición de hipoxia. El ácido tiaprofénico se administró en los 6 perros en forma intravenosa 2 horas antes de extraer los lóbulos. Resultados: No se observó con cambios significativos en la tasa de filtración, periodo de normoxia: 0.42 ñ 0.41, periodo de hipoxia: 0.37 ñ 0.51 ml/min/100 g de tejido pulmonar. La presión arterial pulmonar se incrementó significativamente, normoxia basal: 25.1 ñ 6.21 y durante la hipoxia: 37 ñ 7.19 cm de agua (delta de presión 12.0 ñ 1.2) con P< 0.001. Conclusiones: la reactividad vascular en hipoxia se acentuó significativamente con la administración de ácido tiaprofénico, no se demostró incremento en la permeabilidad vascular pulmonar o incremento en las tasas de filtración capilar

Estudo multicêntrico do nimesulide na reumatologia / Multicenter study with nimesulide in rheumatology

Num estudo multicêntrico, 558 pacientes foram avaliados com o uso do nimesulide em afecçöes reumatológicas. A dose utilizada foi de um comprimido (100mg) duas vezes ao dia durante seis dias. Quanto à eficácia, houve uma acentuada regressäo dos sinais e sintomas avaliados, estatisticamente significante, ao término do estudo. A tolerabilidade do nimesulide foi boa, sendo observadas reaçöes adversas somente em 9,32 por cento dos doentes avaliados

Interaçäo do hormônio antidiurético e das prostaglandinas na progressäo da insuficiência renal experimental / Interaction of antidiuretic hormone and prostaglandins in the progression of experimental renal failure

Utilizamos ratos com diabetes insipidus congênito (Brattlelboro), submetidos a reduçäo de 5/6 da massa renal total, a fim de avaliarmos a participaçäo do hormônio antidiurético (HAD) na funçäo renal do rim remanescente. Verificamos que, na ausência do HAD, näo ocorre hiperfiltraçäo adaptativa, ou seja, a filtraçäo glomerular global se manteve reduzida e a filtraçäo glomerular por néfron foi normal. Esses resultados säo bastante distintos do que ocorre com outras raças de ratos, submetidos a similar reduçäo da massa renal. Paralelamente, avaliamos a participaçäo das prostaglandinas (PGs) neste modêlo, através da inibiçäo deste sistema com indometacina. Também verificamos que na ausência do HAD o bloqueio agudo das PGs näo ocasionou alteraçäo na funçäo renal nestes animais. Diferencialmente, em ratos com HAD (Munich-Wistar, a inhibiçäo das PGs na IRC ocasiona diminuiçäo significativa da hiperfiltraçäo glomerular global e por néfron

Morphine hyperthermia in rats: role of neurochemical substances in brain.

Central neurochemical mechanism underlying the hyperthermic effect of morphine has been investigated in rats. 200 micrograms morphine hydrochloride, when administered through cerebroventricular route at different seasonal air temperature, caused a rise in rectal temperature of rats. This hyperthermia was not affected by prior administration of antiserotonergic (pCPA, 5.6-DHT) or anticatecholaminergic (PBZ, 6-OHDA) drugs, as well as by PGE synthetase inhibitor, indomethacin. Similarity, cholinergic muscarinic or nicotinic receptor blockers, such as atropine and pentolinium/ D-tubocurarine respectively, were ineffective to modify it. Whereas, the depletion of acetylcholine in brain by pretreating the animals with hemicholinium profoundly delayed the hyperthermia, suggesting a central cholinergic involvement in morphine induced hyperthermia in rats.