RESUMO
Several burning questions remain unanswered in pregnancy-related research. Pro- and anti-inflammatory cytokines orchestrate an intriguing interaction leading either to the development of a normal individual or to its rejection. Augmented Th1 cytokines' production is involved in immunological rejection of the foetus. Excessive production of Th1 cytokines, particularly of tumour necrosis factor (TNF)-alpha, also triggers apoptosis. Thus, in the present work we investigated the incidence of apoptosis in a well-known experimental model of Th1-induced abortion, characterized by increased local TNF-alpha levels. Apoptosis of lymphocytes as well as their Th1 and Th2 cytokine production were analysed by flow cytometry. TNF-alpha mRNA levels were additionally analysed by real time reverse transcription-polymerase chain reaction (RT-PCR) in placental and decidual samples. Total placental apoptosis activity was investigated by measuring caspase-3 activity and by TdT-mediated dUTP nick end label staining. Immunohistochemistry, Western blot and real time RT-PCR were used to localize and quantify several anti- and pro-apoptotic molecules at the foetal-maternal interface. Despite elevated Th1 levels at the foetal-maternal interface, mice undergoing abortion presented comparable apoptotic rates. Interestingly, we found a significant upregulation of the anti-apoptotic Bcl-2 protein at the foetal-maternal interface from abortion-prone mice, while no changes could be observed for pro-apoptotic molecules. In the light of our results, we conclude that there is no evidence of increased apoptosis in mice undergoing immunological abortion in spite of elevated TNF-alpha levels. This is probably due to a selective upregulation of anti-apoptotic pathways (i.e. Bcl-2) at the foetal-maternal interface as a compensatory and/or protective mechanism.
Assuntos
Aborto Espontâneo/metabolismo , Placenta/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Aborto Espontâneo/imunologia , Animais , Decídua/imunologia , Decídua/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos CBA , Camundongos Endogâmicos DBA , Placenta/imunologia , Reação em Cadeia da Polimerase , Gravidez , RNA Mensageiro/análise , Células Th1/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética , Regulação para CimaRESUMO
OBJECTIVE: In response to loud clicks, a vestibular evoked potential can be recorded from sternocleidomastoid muscles, called "click evoked myogenic potential" (CEMP). This paper reports on the usefulness of CEMP in the differential diagnosis of acute vertigo of presumed vestibular origin. METHODS: CEMP was examined in 40 patients with acute vertigo of vestibular origin (26 with acute peripheral vestibulopathy, five with Ménière's disease, three with benign paroxysmal positioning vertigo (BPPV), six with psychogenic vertigo) and the results compared with standard caloric reaction (CR). For CEMPs, clicks were delivered unilaterally via a pair of headphones. EMG activity was collected by surface electrodes placed on the sternocleidomastoid belly and averaged. RESULTS: In 29 patients, CR was unilaterally abnormal, pointing to a peripheral vestibular lesion. Seventeen of them had a corresponding loss of CEMPs; the other 12 patients had a normal CEMP. The remaining 11 patients had normal results in both tests. In comparison with CR, CEMP showed a sensitivity of 59% and a specificity of 100% for peripheral vestibular disorders. CONCLUSION: CR is a test of the horizontal canal whereas CEMP is thought to be a sacculus test. Different results of CR and CEMP may be due to this difference between target organs stimulated and may be of prognostic value.