Avaliação dos gangliosídios na regeneração nervosa em ratos / Effect of gangliosides on nerve regeneration in rats

Os autores avaliaram o efeito dos gangliosídios administrados intraperitonealmente na dose de 30mg/kg, por 30 dias, após esmagamento do nervo ciático em ratos. O estudo foi do tipo duplo-cego: nove ratos receberam gangliosídio e 11, solução tamponada pelo mesmo período. Avaliou-se o índice de função do ciático no pré-operatório, primeira, quarta e sexta semanas de pós-operatório, não se encontrando diferença significativa entre os grupos. Avaliou-se a regeneração nervosa histomorfometricamente através da densidade de fibras, percentagem de tecido neural e área média de uma fibra das porções proximais e distais à lesão e do lado normal. Não houve diferenças entre os grupos. A administração dos gangliosídios não interferiu na qualidade da regeneração nervosa.

Altered Expression of Lewis Antigen on Tissue and Erythrocytes in Gastric Cancer Patients

To elucidate the clinical significance of phenotypic alterations of Lewis antigen in gastric cancer patients, we investigated Lewis antigens by analyzing the genotypes of the Le and Se genes and by comparing the results obtained with the phenotypic expression of Lewis antigen in gastric cancer tissue and blood cells. One hundred and twenty gastric cancer patients were examined and compared with respect to Lewis blood phenotype and genotype. The expression of Lea, Leb, sialylated Lea, and sialylated Lex antigens was immunohistochemically examined in uninvolved gastric mucosa, intestinal metaplasia, and cancerous tissue. We also analyzed the significance of Lewis antigen expression by analyzing patient survival. The frequencies of the Lewis phenotypes of RBCs corresponding to Le(a+b-), Le(a-b+), and Le(a-b-) were 16%, 58%, and 26%, respectively. The Le and le allele gene frequencies calculated from genotyping in gastric cancer patients were 0.623 and 0.377, respectively. The frequency for Le(a-b-) of the RBC phenotype had a tendency to be higher in cancer patients than in normal healthy Koreans. However, no difference in the Lewis gene frequency was found between these gastric cancer patients and healthy persons. The phenotype of Le(a-b+) was most prevalent in uninvolved gastric mucosal tissue, whereas the most prevalent form in tumor tissue was Le(a-b-). Sialyl-Lea and sialyl-Lex antigens were hardly detectable in uninvolved gastric mucosa, whereas the two antigens were expressed highly in intestinal metaplastic mucosa and tumor cells. In conclusion, the loss of Lewis antigen expression in tissue and on RBCs in gastric cancer patients is not a result of genetic influences, but rather a result of sialylation in tissue. We also confirm that poor prognosis is associated with dimeric sialyl-Lex and vascular spread.

Postnatal changes in the brain lipids, glycolipids and gangliosides of rats exposed to arrack/ethanol during gestation and lactation.

Effects of exposure of an alcoholic beverage (arrack and its equivalent quantity of alcohol throughout pregnancy and lactation on brain lipids were investigated. Female rats were exposed to arrack (12.00 ml/kg body weigh/day) and ethanol (4.00 g/kg body weight day) before conception and throughout gestation and lactation. For 21 days pups were nursed by their own mothers, afterwards they were fed normal laboratory feed. We found that the level of cholesterol, phospholipids, triacylglycerols, free fatty acids, cerebrosides, ceramide dihexosides, ceramide polyhexosides, sulfatids,, mono and diglycosyl diglycerides and gangliosides were increased in the brain of 21st and 45th day pups. The alterations in the glycolipid profile of the brain persisted even when pups were not directly exposed to alcohol. These alterations in the glycolipid and ganglioside metabolism may be associated with the developmental abnormalities of the brain seen in FAS. The elevation produced in the glycolipid profile of arrack administered pups were more than that caused by its equivalent quantity of ethanol. This suggested an interaction of congeners in the arrack with the alcohol.

Role of lipids in receptor mediated signal transduction.

A new strategy has been successfully applied to reconstitute the brain specific serotonin 5-HT1A receptor-G protein-adenylate cyclase complex. A mild method of tissue preparation gave a stable, membrane-bound form of the receptor (SBP) which retained its natural lipid content. Treatment of SBP with serotonin (1 microM) and 3-[(3-cholamidopropyl) dimethyl ammonio]-1-propanesulphonate (CHAPS) (2%) solubilized the ligand-receptor-G protein-ligand complex along with the associated phospholipids and cholesterol. Dialysis of this extract (SBDS) against buffer containing 25% ethylene glycol produced a stable, reconstituted and active preparation (SBDSE) of vesicles which upon centrifugal separation followed by gentle resuspension retained 95-100% [3H] 8-OH-DPAT binding activity as well as 60% [3H] GppNHp binding and adenylate cyclase activities of SBDSE. The reconstituted receptor preparation compared well with the membrane-bound form in displaying a similar value for KD (2.1 nM) and a single affinity state for [3H] 8-OH-DPAT binding (Bmax = 118 fmol/mg). However, in sharp contrast to the membrane-bound receptor which was negatively coupled to adenylate cyclase, agonist treatment of the solubilized and reconstituted receptor resulted in an increase in adenylate cyclase. This change in receptor-adenylate cyclase coupling following reshuffling of membrane lipids during solubilization and reconstitution suggested that membrane lipids could have a profound effect on receptor-effector coupling. To study the effect of membrane lipid composition on receptor-mediated signal transduction in a stabler and more natural system, neural cells derived from different parts of the brain (hippocampus, HN2; CNS, NCB-20; dorsal root ganglion, F-11) and a non-neural cell line (CHO), all with differing membrane lipid compositions, were selected. Since no known cell line contains the serotonin 5-HT1A receptor (5-HT1A-R), stable transfection of the selected cell lines with a DNA construct encoding the human 5-HT1A-R was carried out and this resulted in a late increase of [3H] 8-OH-DPAT binding in the stationary phase only in the cell lines of neural origin. In the non-neural cell line (CHO), which also displayed marked difference in membrane lipids, the receptor was positively coupled to the phospholipase C-IP3-[Ca2+]i cascade. Even though GPLC was present in the NCB-20 and F-11 cells as evidenced by a bradykinin receptor-mediated increase in inositol phosphates in these cells 8-OH-DPAT treatment resulted in no change in phospholipase C in any of the cell lines of neural origin.(ABSTRACT TRUNCATED AT 400 WORDS)

Identificaçäo da proteina S-100, da enolase neurônio-específica e do gangliosídeo GD3, em melanomas / Identification of S-100 protein, neuron-specific enolase and GD3 gangliosides in melanomas

Os autores procuraram localizar nas células de melanoma a proteína S-100, a enolase neurônio-específica e o gangliosídeo GD3 (Mel-1), através da técnica da imunoperoxidase (PAP). Realizaram o estudo em 38 casos de melanoma clínica e histologicamente classificados como: melanoma superficial extensivo, 19 casos, e melanoma nodular, 19 casos. Os pacientes apresentaram idade variável de 17 a 78 anos; 35 eram brancos e um pardo, sendo 24 do sexo masculino e 14 feminino. A presença nas células tumorais dos antígenos pesquisados näo revelou qualquer correlaçäo com o sexo, idade e o tipo histogenético. Demonstraram a existência de associaçäo significativa da co-expressäo aos pares dos antígenos celulares: proteína S-100 e Mel-1; proteína S-100 e enolase neurônio-específica