Resveratrol-mediated chemoprevention of diethylnitrosamine-initiated hepatocarcinogenesis : Inhibition of cell proliferation and induction of apoptosis

Oil-in-water lipid emulsions: implications for parenteral and ocular delivering systems.

Anthocyanins are known to possess potent anticarcinogenic properties against several cancers thus demonstrating potential for cancer prevention. Black currant (Ribes nigrum L., Grossulariaceae) fruits have a high anthocyanin content. This “superfruit” is known to possess various pharmacological effects including alleviation of chronic oxidative stress and inflammation. In contrast to a large volume of literature on the health benefits of black currant, limited evidence on antitumor effects of black currant exists with virtually no data on the prevention of experimental carcinogenesis. In the current study, we have investigated the chemopreventive effects of an anthocyanin-rich black currant skin extract (BCSE) utilizing our well-characterized model of rat liver carcinogenesis. Initiation of hepatocarcinogenesis was done by intraperitoneal injection of diethylnitrosamine (DENA) followed by promotion with phenobarbital. The rats were exposed to dietary BCSE for 4 weeks prior to initiation, and the treatment was continued for 22 consecutive weeks. BCSE dose-dependently decreased the incidence, total number, multiplicity, size and volume of preneoplastic hepatic nodules. The antihepatocarcinogenic effect of BCSE was confirmed by histopathological examination of liver sections. Immunohistochemical analysis of proliferating cell nuclear antigen and DNA fragmentation revealed BCSE-mediated inhibition of abnormal cell proliferation and induction of apoptosis in DENA-induced rat liver tumorigenesis respectively. Mechanistic studies revealed that BCSE-mediated proapototic signal during experimental hepatocarcinogenesis may be propagated via the up-regulation of Bax and down-regulation of Bcl-2 expression at the translational level. These results along with a safety profile of BCSE encourage the development of black currant bioactive constituents as chemopreventive agents for human liver cancer.

Anthocyanin-rich black currant (Ribes nigrum L.) extract affords chemoprevention against diethylnitrosamine-induced hepatocellular carcinogenesis in rats

AIM: To investigate the chemopreventive effects of 1α, 25-dihydroxyvitamin D3 in diethylnitrosamine induced, phenobarbital promoted rat hepatocarcinogenesis.

METHODS: The rats were randomly divided into 6 different groups (A-F). Groups A, C and E rats received a single intraperitoneal (i.p) injection of diethylnitrosamine (DEN) at a dose of 200 mg/kg body mass in 9 g/L NaCl solution at 4 wk of age, while group B served as normal vehicle control received normal saline once. After a brief recovery of 2 wk, all the DEN treated rats were given phenobarbital (PB) at 0.5 g/L daily in the basal diet till wk 20. Group A was DEN control. Treatment of 1α, 25-(OH)2D3 in group C was started 4 wk prior to DEN injection and continued thereafter till wk 20 at a dose of 0.3 μg/100 μL propylene glycol per one single dose (os) twice a week. Group E received the treatment of 1α, 25-(OH)2D3 at the same dose mentioned as above for 15 wk. The rats in group D and F received 1α, 25-(OH)2D3 alone as in group C without DEN injection.

RESULTS: The comet assay showed statistically higher mean values for length to width ratios (L: W) of DNA mass and tailed cells (P < 0.01; P < 0.01 respectively) in DEN treated rats as compared to their normal controls. Continuous supplementation of 1α, 25-dihydroxyvitaminD3 showed a significant (P < 0.01) decrease in L:W ratio of DNA mass tailed cells. Furthermore, 1α, 25-(OH)2D3 supplementations elevated the super oxide dismutase (SOD) activity, hepatic malondialdehyde (MDA) level, reduced glutathione (GSH) and glutathione S-transferase (GST) activity (P < 0.01, P < 0.05, P < 0.05 and P < 0.05 respectively). As an endpoint marker histological changes were observed to establish the chemopreventive effects of 1α, 25-dihydroxyvitaminD3.

CONCLUSION: Supplementations of 1α, 25-(OH)2D3 has a marked protection against hepatic nodulogenesis, antioxidant enzymes and DNA damages in DEN induced rat hepatocarcinogenesis promoted by phenobarbital.

1α, 25-dihydroxyvitamin D3 prevents DNA damage and restores antioxidant enzymes in rat hepatocarcinogenesis induced by diethylnitrosamine and promoted by phenobarbital

Current evidence indicates that ω-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid and docosahexaenoic acid found in fish oil, can prevent the development of inflammatory diseases by affecting different steps of the immune response. The capacity of ω-3 PUFAs to modulate synthesis of eicosanoids, activity of nuclear receptor and nuclear transcription factors, and production of resolvins may also mitigate inflammatory processes already present. Parenteral infusion of ω-3 PUFAs is advantageous, particularly in severely ill patients, because the fatty acids are rapidly incorporated by cells. In addition, when fatty acids are given parenterally, there are no losses from digestion and absorption as there are with enteral infusion. Recently, lipid emulsions enriched with ω-3 fish oil have been introduced as a component of parenteral nutrition. Currently, there is one lipid emulsion that contains only fish oil; it is infused together with conventionally used lipid emulsions. Other commerc...

Fish Oil Lipid Emulsions and Immune Response: What Clinicians Need to Know

Influence of Medium-Chain Triglyceride- Based Lipid Emulsion on Rat Polymorphonuclear Cell Functions

A new organizational structure for hospitaIs is proposed based on functional or geographical specialized areas. The manager of each specialized area is responsible for specific decisions in his own area and ali of them integrate a body to discuss technical and administrative matters and where general decisions are assumed.

http://www.scielo.br/pdf/rae/v38n1/a08v38n1.pdf

Desevolvimento de uma estratégia de manufatura em um ambiente turbulento

1. The effect of different nutritional situations on the growth of experimental Walker 256 carcinosarcoma was investigated in rats. Fifty adult male Wistar rats were randomly assigned to three groups: group NN received standard chow throughout the experiment; group DD initially received an isocaloric protein-free diet, and some of the animals in this group (DN) were fed normal chow from the 37th to the 53rd day of the study. 2. On the 42nd day of the experiments all animals were inoculated subcutaneously in the flank with 2.5 to 3.0 x 10(5) viable Walker 256 carcinosarcoma cells and tumor growth and rat body weight were monitored daily thereafter. 3. Significantly greater tumor growth was detected in well-nourished (group NNT) as compared with malnourished animals (group DDT), but not in protein-depleted-refed (group DNT) animals, whose tumor growth was not significantly different from that of constantly malnourished (group DDT) rats. 4. Comparison of tumor weight and of the tumor weight/carcass weight (TW/CW) ratio showed no significant difference between malnourished and malnourished/refed animals, whereas well-nourished animals showed higher tumor weight and TW/CW ratios. 5. TW/CW curves for malnourished rats were parallel to those for malnourished/refed rats. TW/CW curves for constantly malnourished rats differed from those for well-nourished rats during the first observation period but there was no difference during the second week of tumor growth. 6. Although the protein-free diet inhibited tumor growth and refeeding enhanced it, carcass weight increased at the same rate, and therefore no change was observed in the TW/CW ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of diets with different protein levels on the growth of Walker 256 carcinosarcoma in rats.

/pdf/pedagogia-e-didactica-relacoes-e-aplicacoes-no-ensino-medico-3x13bztgon.pdf

Pedagogia e didactica: relacoes e aplicacoes no ensino medico

O numero de leitos hospitalares a disposicao de uma comunidade representa importante fator de limitacao do nivel de assistencia medica que lhe e possivel oferecer. Uma dificuldade inicial, em termos de realidade "brasileira, e a carencia de estudos capazes de indicar os quantitativos de leitos hospitalares, gerais e especializados, necessarios ao atendimento da populacao no Brasil. Dai a necessidade de os autores se valerem de dados que representam a transposicao de numeros estrangeiros, os quais sao, por isso mesmo, passiveis de critica. Mesmo com essa limitacao, parece razoavel definir como necessidade minima o numero de 4 leitos por 1000 habitantes, quando se trata de leitos gerais nao especializados, de 1,5/1000 para obstetricia e 1/1000 para pediatria. A analise realizada, da assistencia hospitalar prestada aos segurados do Instituto Nacional de Previdencia Social, no Estado de Sao Paulo, permite algumas observacoes: 1 - existencia de consideravel numero de municipios onde nao existe siquer um estabelecimento hospitalar; 2 - relacao de 1,95 leitos por 1000 segurados do INPS, quando se faz uma avaliacao global, numero inferior a metade do indice minimo estabelecido; 3 - carencia ainda mais grave, quando se analisam os dados separadamente para clinica medica e cirurgica, obstetricia e pediatria; 4 - a maior deficiencia de leitos, em relacao as regioes administrativas do Estado, refere-se a Grande Sao Paulo, quer quanto ao numero global de leitos, quer quanto ao de leitos pelas especialidades acima referidas; 5 - em relacao a psiquiatria, o indice encontrado, para atendimento da populacao previdenciaria, e de 0,51 leitos/1000 usuarios, o qual corresponde a 1/10 da relacao aceita internacionalmente como razoavel; 6 - no que se refere a tisiologia, esse indice e de 0,14 leitos/1000 habitantes; 7 - considerando-se que o INPS ja mantem convenio com cerca de 90% dos hospitais particulares do Estado, os indices apresentados devem corresponder aproximadamente aos disponiveis para toda a populacao, quando sao incluidos todos os leitos disponiveis.

/pdf/assistencia-hospitalar-no-ambito-da-previdencia-social-no-2onzugyap5.pdf

Ernesto Lima Gonçalves

Papers

Influence of Medium-Chain Triglyceride- Based Lipid Emulsion on Rat Polymorphonuclear Cell Functions

Desevolvimento de uma estratégia de manufatura em um ambiente turbulento

Effect of diets with different protein levels on the growth of Walker 256 carcinosarcoma in rats.

Pedagogia e didactica: relacoes e aplicacoes no ensino medico

Assistência hospitalar no âmbito da previdência social no Estado de São Paulo, Brasil