Aspectos inmunológicos en la depresión / Immunological aspects in the depression

Existe evidencia que el sistema inmune puede modular tanto los neurotransmisores a nivel central como la respuesta endocrina, interrelación que explicaría los síntomas de la depresión. Se analizaron una serie de investigaciones que relacionaban la depresión y función inmune predominando hallazgos heterogéneos. Se ha descrito un patrón de citoquinas similar al del cáncer, como posible perfil depresivo carcinógeno de las citoquinas. Por otro lado, existe una hiperfunción del eje hipotálamo, hipófisis suprarrenal con alteración de la retroalimentación negativa. A pesar de estos avances, existe controversia acerca de la relación causal entre el estado pro inflamatorio y las alteraciones conductuales de la depresión, necesitándose esclarecer si los cambios inmunológicos son directamente responsables de la alteración de los neurotransmisores a nivel central. Se reportó cómo diversos antidepresivos modifican la hiperactividad del eje y modifican la inmunidad humoral y celular, abriendo la posibilidad de modular la respuesta inmune a través de estos fármacos.

There is evidence that immune system modulates neurotransmitters at central level as well as the endocrine response, interrelation that would explain the depression symptoms. A series of investigations that related the depression and immune function was analyzed, predominating heterogeneous findings. A pattern of cytokines has been described as similar as the one of cancer, suggesting a depressive carcinogenic cytokines profile. On the other hand, a hyperfuntion of the hypothalamus, hypofisis adrenal axis, with alteration of the negative feedback exists in these patients. Despite of these advances, controversy about the causal relationship between the pro inflammatory state and the behavior alterations of depression exists, being needed to clarify if the immunological changes are directly responsible for the neurotransmitters alteration at central level. It was reported how diverse antidepressants modify the hyperactivity of axis and modify the humoral and cellular immunity, opening the possibility of modulating the immune response through these drugs.

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

Glucocorticoids (Gc) influence the differentiation of neural crest-derived cells such as those composing sympathoadrenal tumors like pheochromocytomas, as well as neuroblastomas and gangliomas. In order to obtain further information on the effects of Gc on cells evolving from the neural crest, we have used the human neuroblastoma cell line SK-N-SH to analyze: 1) the presence and the binding characteristics of Gc receptors in these cells, 2) the effect of dexamethasone (Dex) on the migration of SK-N-SH cells, and 3) the effect of Dex on the organization of the cytoskeleton of SK-N-SH cells. We show that: 1) receptors that bind [³H]-Dex with high affinity and high capacity (Kd of 9.6 nM, Bmax of 47 fmol/mg cytosolic protein, corresponding to 28,303 sites/cell) are present in cytosolic preparations of SK-N-SH cells, and 2) treatment with Dex (in the range of 10 nM to 1 æM) has an inhibitory effect (from 100 percent to 74 and 43 percent, respectively) on the chemotaxis of SK-N-SH cells elicited by fetal bovine serum. This inhibition is completely reversed by the Gc receptor antagonist RU486 (1 æM), and 3) as demonstrated by fluorescent phalloidin-actin detection, the effect of Dex (100 nM) on SK-N-SH cell migration is accompanied by modifications of the cytoskeleton organization that appear with stress fibers. These modifications did not take place in the presence of 1 æM RU486. The present data demonstrate for the first time that Dex affects the migration of neuroblastoma cells as well as their cytoskeleton organization by interacting with specific receptors. These findings provide new insights on the mechanism(s) of action of Gc on cells originating in the neural crest.

Steroid receptors in Brazilian patients with large bowel cancer

1. Twenty-two colorectal carcinomas were examined for the presence of estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a charcoal dextran assay. 2. ER was detected in 4/13 (31 per cent ) and 5/9 (56 per cent ) of the rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa presented similar incidence and ER density values within the tumor ranges. 3. The incidence of PR-positive samples was also higher in colon than in rectal carcinomas (44 per cent vs 23 per cent ). Normal mucosa displayed significantly higher PR titers than the corresponding tumor tissue. It seems reasonable to assume that normal colorectal mucosa may be one of the target tissues of progesterone activity. Most tumor biopsies and normal mucosa were completely AR negative, whilst GR was present in a larger fraction (63 per cent ) of tumoral specimens, occurring more commonly in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms than in normal mucosa (54 per cent vs 38 per cent in rectum and 78 per cent vs 56 per cent in colon), suggesting that glucocorticoids may be involved in the control of tumor-cell proliferation. 4. Our findings which indicate low densities of ER, PR, and absence of AR in some large bowel cancers, suggest sex hormone and endocrine independence for those cancers. The role of glucocorticoid receptors in those forms of cancer remains to be elucidated

Regulaçäo dos receptores de glicocorticóide em leucócitos mononucleares humanos / Glucocorticoid receptores of human mononuclear leukocytes

O presente estudo foi realizado com a finalidade de analisar receptores de glicocorticóide em leucócitos mononucleares (MNL) de sangue periférico de indivíduos normais, näo tratados e de indivíduos normal aos quais foram administrados exogenamente os corticóides: prednisona e deflazacort. MNL de mulheres e homens normais apresentaram uma concentraçäo de receptores de glicocorticóide de 7,52 ñ 2,5fMol/10**6 cel e uma constante de dissociaçäo (Kd) de 9,5 ñ 2,3nM. Näo houve diferença em relaçäo ao sexo e as fases do ciclo menstrual. Em indivíduos tratados com predinisona, näo houve mudança nos parâmetros de ligaçäo. A administraçäo deflazacort determinou uma sensível reduçäo dos sítios de ligaçäo. Concluímos que certos glicocorticóides podem exercer um efeito regulatório sobre seus receptores

Steroid receptors in meningiomas

Dados epidemiológicos sugerem uma associaçäo entre meningiomas e hormônios sexuais. Há preponderância da incidência da incidência destes tumores em mulheres, sendo diagnosticados mais frequentemente entre 35 e 55 anos. Progressäo tumoral pode ocorrer durante a gravidez e a associaçäo entre meningiomas e câncer de mama é estatisticamente significativa. O efeito benéfico positivo dos glicocorticóides no tratamento clínico de tumores intracranianos está bem documentado, embora este efeito seja relacionado com o edema cerebral e näo com proliferaçäo tumoral. A presença de receptores intracelulares específicos parece ser condiçäo necessaria embora näo suficiente para a expressäo dos efeitos celulares destes esteróides. O objetivo do nosso trabalho foi a determinaçäo de receptores de estrógeno (ER), progesterona (PR), andrógeno (AR) e glicocorticóide (GR) em 10 meningiomas através da metodologia do carväo-dextrana. Neste estudo verificamos que somente 20% dos meningiomas contém receptores de estrógeno e as concentraçöes determinadas säo baixas. Receptores de progesterona estäo presentes em 90% dos tumores, em alta concentraçäo (média + ou - dp = 60 + ou - 38 fMol/mg prot). Cerca de 70% dos meningiomas contém níveis intermediários de AR e GR. Testes de competiçäo demonstram que todos os receptores säo específicos. Incidência e concentraçäo de todos os receptores säo maiores em pacientes do sexo feminino. A ocorrência de receptores de progesterona, andrógeno e glicocorticóide pode indicar a possível utilidade de manipulaçäo endócrinas em meningiomas näo operáveis