Stress hormones concentrations in the normal microenvironment predict risk for chemically induced cancer in rats.

Evidence show that stress hormones can influence cancer progression, but its role in carcinogenesis is poorly understood. In this study, we used a new method based on oral carcinogenesis model in rats to test the hypothesis that physiological levels of stress hormones in the normal tissue microenvironment would have significant predictive value for chemically induced cancer occurrence. Male Wistar rats were submitted to a tongue biopsy for measuring not-stress induced levels of norepinephrine, corticosterone, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) in the tissue before carcinogenic induction. Rats were treated with the 4-nitroquinoline-1-oxide (4NQO) chemical carcinogen for twenty weeks and then euthanized for microscopic evaluation of the tongue lesions. Increased pre-carcinogen norepinephrine concentrations and reduced basal corticosterone levels in the normal tissue microenvironment were predictive for oral squamous cell carcinoma (OSCC) occurrence. Likewise, increased pre-carcinogen norepinephrine levels in the normal microenvironment were associated a lower expression of pCDKN2a-p16 in OSCCs. Post-carcinogen levels of corticosterone and BDNF in oral leukoplakia tissues (precursor lesion of OSCC) and post-carcinogen corticosterone concentrations in OSCCs were higher than basal levels in the normal mucosa. Increased norepinephrine concentrations in OSCCs were associated to a greater tumor volume and thickness. Furthermore, higher levels of norepinephrine, ACTH and BDNF in OSCCs were associated to a lesser intensity of the lymphoplasmocytic infiltrate. This study shows that pre-carcinogen stress hormones levels in the normal microenvironment may be predictive for chemically induced cancer in rats. Moreover, chemical carcinogenesis can promote stressor-like effects with hormonal changes in the tissue microenvironment, which may be associated to tumor progression.

Alteração do índice biespectral antes e após estimulação elétrica ou mecânica em cães anestesiados pelo isofluorano / Bispectral index changes before and after electrical or mechanical stimulation in isoflurane-anesthetized dogs

Uma das formas atuais para se avaliar o grau de hipnose e depressão do sistema nervoso central durante a anestesia é o índice biespectral (BIS), que fornece um valor de 0 a 100. Objetivou-se avaliar as alterações do BIS de cães durante a estimulação elétrica e mecânica supra-máxima e sob diferentes concentrações de isofluorano, a fim de verificar se existe uma relação entre este índice e a resposta motora frente à nocicepção. Utilizaram-se sete cães da raça Beagle, dois machos e cinco fêmeas, anestesiados com isofluorano nas concentrações de 2,0; 1,8; 1,6; 1,4 e 1,2%. Os diferentes tipos de estímulo foram utilizados em procedimentos anestésicos diferentes nos mesmos animais, com intervalo mínimo de 15 dias. Os valores de BIS foram anotados por 60 segundos em cada avaliação, derivando médias antes (AE) e depois (DE) de cada estímulo. Os resultados foram analisados por meio de teste t pareado ou Wilcoxon pareado (P<0,05). Houve diferença significativa entre os valores AE e DE em todas as concentrações de isofluorano, exceto 2,0% no estímulo mecânico. Também foi significativa entre a subtração desses valores, quando comparados entre estímulos, em 1,8 e 2,0%. Conclui-se que a resposta frente a estímulos supra-máximos modifica os valores de BIS em cães por meio da superficialização do plano anestésico. Sugere-se o emprego do modelo mecânico para evitar possíveis interferências de corrente elétrica e perda da confiabilidade dos dados.

One of the current methods to assess hypnosis and central depression during anesthesia is the bispectral index (BIS), which generates a number from 0 to 100. The purpose of the present study was to evaluate the changes in BIS during electrical or mechanical supra-maximal stimulation in order to investigate whether there is a relation between this index and motor response to nociception. Seven beagle dogs were included, two males and five females, which were anesthetized with isoflurane at 2.0, 1.8, 1.6, 1.4 and 1.2%. Different types of stimuli were employed at different procedures in the same animals with at least 15 days of interval. The BIS values were recorded during 60 seconds each time and mean values were obtained before (AE) and after (DE) the stimulus. Results were compared through paired t test or Wilcoxon's paired test (P<0.05). Significant differences were found between AE and DE values in almost every isoflurane concentration, as well as between the subtraction of these values, when compared between types of stimuli at 1.8 and 2.0%. In conclusion, the response to supra-maximal stimulation does change BIS values in dogs by decreasing the depth of anesthesia. The use of mechanical stimulation is suggested in order to avoid possible interferences of the electrical current and loss of data reliability.