Changes in red blood cell osmotic fragility induced by total plasma and plasma fractions obtained from rats bearing progressive and regressive variants of the Walker 256 tumor

Two variants (A and B) of the widely employed Walker 256 rat tumor cells are known. When inoculated sc, the A variant produces solid, invasive, highly metastasizing tumors that cause severe systemic effects and death. We have obtained a regressive variant (AR) whose sc growth is slower, resulting in 70-80% regression followed by development of immunity against A and AR variants. Simultaneously with the beginning of tumor regression, a temporary anemia developed (~8 days duration), accompanied by marked splenomegaly (~300%) and changes in red blood cell osmotic fragility, with mean corpuscular fragility increasing from 4.1 to 6.5 g/l NaCl. The possibility was raised that plasma factors associated with the immune response induced these changes. In the present study, we identify and compare the osmotic fragility increasing activity of plasma fractions obtained from A and AR tumor bearers at different stages of tumor development. The results showed that by day 4 compounds precipitating in 60% (NH4)2SO4 and able to increase red blood cell osmotic fragility appeared in the plasma of A and AR tumor bearers. Later, these compounds disappeared from the plasma of A tumor bearers but slightly increased in the plasma of AR tumor bearers. Furthermore, by day 10, compounds precipitating between 60 and 80% (NH4)2SO4 and with similar effects appeared only in plasma of AR tumor bearers. The salt solubility, production kinetics and hemolytic activity of these compounds resemble those of the immunoglobulins. This, together with their preferential increase in rats bearing the AR variant, suggest their association with an immune response against this tumor.

Decorin is one of the proteoglycans expressed in Walker 256 rat mammary carcinoma

Proteoglycan and glycosaminoglycan content was analyzed in a model of rat mammary carcinoma to study the roles of these compounds in tumorigenesis. Hyaluronic acid and proteoglycans bearing chondroitin and/or dermatan sulfate chains were detected in solid tumors obtained after subcutaneous inoculation of Walker 256 rat carcinoma cells. About 10% of sulfated glycosaminoglycan chains corresponded to heparan sulfate. The small leucine-rich proteoglycan, decorin, was identified as one of the proteoglycans, in addition to others of higher molecular weight, by cross-reaction with an antiserum raised against pig laryngeal decorin and by N-terminal amino acid sequencing. Decorin was separated from other proteoglycans by hydrophobic chromatography and its complete structure was determined. It has a molecular weight of about 85 kDa and a dermatan chain of 45 kDa with 4-sulfated disaccharides. After degradation of the glycosaminoglycan chain, three core proteins of different molecular weight (36, 46 and 56 kDa) were identified. The presence of hyaluronic acid and decorin has been reported in a variety of tumors and tumor cells. In the Walker 256 mammary carcinoma model, hyaluronic acid may play an important role in tumor progression, since it provides a more hydrated extracellular matrix. On the other hand, decorin, which is expressed by stromal cells, represents a host defense response to tumor growth.

Participation of the NO/cGMP/K+ATP pathway in the antinociception induced by Walker tumor bearing in rats

Implantation of Walker 256 tumor decreases acute systemic inflammation in rats. Inflammatory hyperalgesia is one of the most important events of acute inflammation. The L-arginine/NO/cGMP/K+ATP pathway has been proposed as the mechanism of peripheral antinociception mediated by several drugs and physical exercise. The objective of this study was to investigate a possible involvement of the NO/cGMP/K+ATP pathway in antinociception induced in Walker 256 tumor-bearing male Wistar rats (180-220 g). The groups consisted of 5-6 animals. Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. Walker tumor (4th and 7th day post-implantation) reduced prostaglandin E2- (PGE2, 400 ng/paw; 50 µL; intraplantar injection) and carrageenan-induced hypernociception (500 µg/paw; 100 µL; intraplantar injection). Walker tumor-induced analgesia was reversed (99.3% for carrageenan and 77.2% for PGE2) by a selective inhibitor of nitric oxide synthase (L-NAME; 90 mg/kg, ip) and L-arginine (200 mg/kg, ip), which prevented (80% for carrageenan and 65% for PGE2) the effect of L-NAME. Treatment with the soluble guanylyl cyclase inhibitor ODQ (100% for carrageenan and 95% for PGE2; 8 µg/paw) and the ATP-sensitive K+ channel (KATP) blocker glibenclamide (87.5% for carrageenan and 100% for PGE2; 160 µg/paw) reversed the antinociceptive effect of tumor bearing in a statistically significant manner (P < 0.05). The present study confirmed an intrinsic peripheral antinociceptive effect of Walker tumor bearing in rats. This antinociceptive effect seemed to be mediated by activation of the NO/cGMP pathway followed by the opening of KATP channels.

Tumor growth reduction is regulated at the gene level in Walker 256 tumor-bearing rats supplemented with fish oil rich in EPA and DHA

We investigated the effect of fish oil (FO) supplementation on tumor growth, cyclooxygenase 2 (COX-2), peroxisome proliferator-activated receptor gamma (PPARγ), and RelA gene and protein expression in Walker 256 tumor-bearing rats. Male Wistar rats (70 days old) were fed with regular chow (group W) or chow supplemented with 1 g/kg body weight FO daily (group WFO) until they reached 100 days of age. Both groups were then inoculated with a suspension of Walker 256 ascitic tumor cells (3×107 cells/mL). After 14 days the rats were killed, total RNA was isolated from the tumor tissue, and relative mRNA expression was measured using the 2-ΔΔCT method. FO significantly decreased tumor growth (W=13.18±1.58 vsWFO=5.40±0.88 g, P<0.05). FO supplementation also resulted in a significant decrease in COX-2 (W=100.1±1.62 vsWFO=59.39±5.53, P<0.001) and PPARγ (W=100.4±1.04vs WFO=88.22±1.46, P<0.05) protein expression. Relative mRNA expression was W=1.06±0.022 vsWFO=0.31±0.04 (P<0.001) for COX-2, W=1.08±0.02vs WFO=0.52±0.08 (P<0.001) for PPARγ, and W=1.04±0.02 vs WFO=0.82±0.04 (P<0.05) for RelA. FO reduced tumor growth by attenuating inflammatory gene expression associated with carcinogenesis.

Lei e ordem econômica no pensamento de John R. Commons

The paper has analyzed John R. Commons' contribution to the comprehension of Law and Economics relationship. In contrast to the orthodox economics, Commons has shown that the capitalist economic order emerges and functions regulated by laws and institutions. These approaches made possible to him to understand the nature of the modern capitalist wealth and the problems that time introduces in economic transactions.

Continuidade ou ruptura? Uma análise de alguns aspectos da filosofia social de John Stuart Mill, Alfred Marshall e John Maynard Keynes

O artigo argumenta que é possível se falar em uma 'tradição' no campo de filosofia social e econômica unindo as obras de J.S. Mill e Alfred Marshall e J.M. Keynes. Essa 'tradição' pode ser caracterizada pelas seguintes concepções: (a) pela rejeição moral aos valores aquisitivos do capitalismo; (b) pela visão de que o sistema capitalista seria incapaz de resolver de forma espontânea as questões das desigualdades de renda e riqueza e da pobreza; (c) pela ideia de que, por uma questão de garantia de liberdade e da diversidade, além de por questões de eficiência econômica, dever-se-ia deixar a iniciativa individual agir livremente nas esferas em que é capaz de engendrar bons resultados, mas que o Estado deveria intervir, quando essa falha, atuando em benefício da coletividade; (d) pela crença de que seria possível melhorar significativamente esse sistema por meio de mudanças pontuais e graduais.

Teoria da justiça de John Jawls: entre o liberalismo e o comunitarismo

O objetivo do presente artigo é realizar uma análise da teoria da justiça como eqüidade de John Rawls em A Theory of Justice e no Political Liberalism, destacando seu modelo de complementaridade entre o deontológico e o procedimental com o teleológico e substancial, buscando responder algumas das críticas levantadas por autores comunitaristas à teoria rawlsiana de justiça e procurando apontar para suas semelhanças. Parto das críticas dos comunitaristas à teoria da justiça como eqüidade; posteriormente, analiso os aspectos teleológicos contidos em seu modelo deontológico; em seguida, destaco a intrínseca relação entre o procedimental e o substancial; por fim, apresento as respostas às críticas comunitaristas à Rawls, destacando a especificidade de sua concepção de justiça.

Posição original e equilíbrio reflexivo em John Rawls: o problema da justificação

O objetivo deste artigo é estabelecer algumas considerações sobre o papel dos procedimentos de posição original e equilíbrio reflexivo na teoria da justiça como equidade de John Rawls, nas obras A Theory of Justice, Political Liberalism e Justice as Fairness: A Restatement. Eu pretendo mostrar que Rawls faz uso de um modelo coerentista-pragmático de justificação dos princípios de justiça em um âmbito público, que é não-fundacionalista em razão da interconexão entre estes procedimentos.

John Locke e o argumento da economia para a tolerância

O objetivo deste texto é analisar o argumento da economia que justificaria a tolerância como um dos maiores fatores para o desenvolvimento dos povos, no século XVII, segundo a interpretação de Locke. Expressando de outro modo, este texto pretende responder a seguinte questão: qual o lugar da dimensão econômica na teoria lockiana sobre a tolerância?

Oscilações entre o reducionismo e o fisicalismo não-redutivo no naturalismo biológico de John Searle

O artigo examina a concepção de Searle sobre a redução da consciência (em especial a sua teoria acerca de seus poderes causais), que se mostra obscura e incoerente. Porém, essa incoerência não é inevitável, pois o naturalismo biológico possui elementos que permitiriam a articulação de uma teoria mais clara a respeito das capacidades causais. O exame da teoria de Pereboom e Kornblith possibilita entender por que a afirmação de identidade das capacidades causais leva a um reducionismo. Essa teoria aponta um caminho promissor para que se possa aprimorar o naturalismo biológico.