RESUMO
Loss of function of the peritoneal membrane is associated with peritonitis. Adenosine levels in sites of inflammation were shown to increase and exhibit immunoregulatory effects. Our aim was to elucidate the regulatory role of adenosine during peritonitis and to test the involvement of peritoneal mesothelial cells (PMC) in adenosine regulation. In a mice model of Escherichia coli peritonitis, the adenosine A(2A) receptor (A(2A)R) agonist (CGS21680) prevented leukocyte recruitment and reduced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Peritonitis induced the elevation of adenosine with a peak at 24 h. Analysis of adenosine receptor levels on peritoneum showed that A(1) receptor (A(1)R) protein levels peak at 12 h after inoculation and then return to baseline at 24 h, whereas high affinity A(2A)R protein levels peak at 24 h concomitantly with the peak of adenosine concentration. Low affinity A(2B) receptor (A(2B)R) levels elevated slowly, remaining elevated up to 48 h. In human PMC (HPMC), the early cytokines, IL-1-alpha, and TNF-alpha upregulated the A(2B) and A(2A) receptors. However, interferon-gamma (IFN-gamma) upregulated the A(2B)R and decreased A(2A)R levels. Treatment with the A(2A)R agonist reduced IL-1-dependent IL-6 secretion from HPMC. In conclusion, the kinetics of adenosine receptors suggest that at early stage of peritonitis, the A(1)R dominates, and later its dominance is replaced by the G stimulatory (Gs) protein-coupled A(2A)R that suppresses inflammation. Early proinflammatory cytokines are an inducer of the A(2A)R and this receptor reduces their production and leukocyte recruitment. Future treatment with adenosine agonists should be considered for attenuating the damage to mesothelium during the course of acute peritonitis.
Assuntos
Adenosina/metabolismo , Inflamação/genética , Peritonite/imunologia , Peritonite/metabolismo , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Agonistas do Receptor A1 de Adenosina , Agonistas do Receptor A2 de Adenosina , Antagonistas do Receptor A2 de Adenosina , Animais , Anti-Hipertensivos/farmacologia , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Escherichia coli , Feminino , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Camundongos , Camundongos Endogâmicos , Peritonite/microbiologia , Fenetilaminas/farmacologia , Agonistas do Receptor Purinérgico P1 , Antagonistas de Receptores Purinérgicos P1 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Purinérgicos P1/genética , Receptores Purinérgicos P1/metabolismo , Teobromina/análogos & derivados , Teobromina/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Xantinas/farmacologiaRESUMO
Israel's "Treatment of Mentally Sick Persons Law" of 1955 was repealed and replaced by the "Treatment of Mental Patients Law" of 1991. Under the latter, the "Compulsory Hospitalization Order" (CHO) defines the new order based on accumulated experience with the old legislation, and on the philosophy that considers the CHO one of the most severely oppressive forms of deprivation of human liberty and rights. The new order sets limits and boundaries for CHO, guarding the rights of those unavoidably committed by force. According to the new law, the district psychiatrist decides upon and issues the order, while the tribunal (District Psychiatric Committee) considers appeals. The order is limited to 1 week, with an option for the district psychiatrist to prolong it on written request for up to 14 days. The tribunal can later prolong the order further. The objective of this study was to review changes that have occurred following enforcement of the new law in the Jerusalem district. A comparison was made between CHO's issued the year before the new legislation took effect and the year after. The comparison included review of all CHO's and medical files of all patients hospitalized by coercion during 1990 and 1992. It was assumed that there would be a decline in rate and length of hospitalization of patients forced to be committed by the new law. The main findings refuted this hypothesis. In 1992 there was an increase of 38% in the number of compulsory hospitalizations. This increase derived mainly from increased demands for CHO's from psychiatric emergency rooms. There was also an increase in patients hospitalized by order of the District Psychiatric Committee using its authority under section 10(C) of the law. Conversely, length of compulsory hospitalization was shorter under the new law. In light of these findings, it would seem that the new law has only partially fulfilled expectations of reform in individual rights. There is need for further evaluation and follow-up of the CHO in order to determine whether the "Treatment of Mental Patients Law" of 1991 has in fact fulfilled its objectives. Furthermore, it is necessary to determine means, medical or legal, that may possibly advance further the prospective of human rights while maintaining a suitable balance between civil liberties and clinical needs, of over-confinement versus under-treatment, which may lead to neglect or danger.