Low doses of monocrotaline in rats cause diminished bone marrow cellularity and compromised nitric oxide production by peritoneal macrophages

Monocrotaline (MCT) is a pyrrolizidine alkaloid found in a variety of plants. The main symptoms of MCT toxicosis in livestock are related to hepato- and nephrotoxicity; in rodents and humans, the induction of a pulmonary hypertensive state that progresses to cor pulmonale has received much attention. Although studies have shown that MCT can cause effects on cellular functions that would be critical to those of lymphocytes/macrophages during a normal immune response, no immunotoxicological study on MCT have yet to ever be performed. Thus, the aim of the present study was to evaluate the effect of MCT on different branches of the immune system using the rat - which is known to be sensitive to the effects of MCT - as the model. Rats were treated once a day by gavage with 0.0, 0.3, 1.0, 3.0, or 5.0 mg MCT/kg for 14 days, and then any effects of the alkaloid on lymphoid organs, acquired immune responses, and macrophage activity were evaluated. No alterations in the relative weight of lymphoid organs were observed; however, diminished bone marrow cellularity in rats treated with the alkaloid was observed. MCT did not affect humoral or cellular immune responses. When macrophages were evaluated, treatments with MCT caused no significant alterations in phagocytic function or in hydrogen peroxide (H(2)O(2)) production; however, the MCT did cause compromised nitric oxide (NO) release by these cells.

Hematopoietic response of rats exposed to the impact of an acute psychophysiological stressor on responsiveness to an in vivo challenge with Listeria monocytogenes: Modulation by Chlorella vulgaris prophylactic treatment

In this study, we investigated the hematopoietic response of rats pretreated with CV and exposed to the impact of acute escapable, inescapable or psychogenical stress on responsiveness to an in vivo challenge with Listeria monocytogenes. No consistent changes were observed after exposure to escapable footshock. Conversely, the impact of uncontrollable stress (inescapable and psychogenical) was manifested by an early onset and increased severity and duration of myrelossuppression produced by the infection. Small size CFU-CM colonies and increased numbers of clusters were observed, concurrently to a greater expansion in the more mature population of bone marrow granulocytes. No differences were observed between the responses of both uncontrollable stress regimens. CV prevented the myelossuppression caused by stress/infection due to increased numbers of CFU-GM in the bone marrow. Colonies of cells tightly packed, with a very condensed nucleus; in association with a greater expansion in the more immature population of bone marrow granulocytes were observed. Investigation of the production of colony-stimulating factors revealed increased colony-stimulating activity (CSA) in the serum of normal and infected/stressed rats treated with the algae. CV treatment restored/enhanced the changes produced by stress/infection in total and differential bone marrow and peripheral cells counts. Further studies demonstrated that INF-gamma is significantly reduced, whereas IL-10 is significantly increased after exposure to Uncontrollable stress. Treatment with CV significantly increased INF-gamma levels and diminished the levels of IL-10. Uncontrollable stress reduced the protection afforded by CV to a lethal dose of L. monocytogenes, with survival rates being reduced from (50%) in infected rats to 20% in infected/stressed rats. All together, our results suggest Chlorella treatment as an effective tool for the prophylaxis of post-stress myelossupression, including the detrimental effect of stress on the course and outcome of infections. (C) 2008 Elsevier Inc. All rights reserved.

Erbium, chromium : yttrium scandium gallium garnet laser for caries removal: influence on bonding of a self-etching adhesive system

This study evaluated the influence of the dental substrates obtained after the use of different caries removal techniques on bonding of a self-etching system. Forty, extracted, carious, human molars were ground to expose flat surfaces containing caries-infected dentine surrounded by sound dentine. The caries lesions of the specimens were removed or not (control-G1) either by round steel burs and water-cooled, low speed, handpiece (G2), or by irradiation with an erbium, chromium:yttrium scandium gallium garnet (Er,Cr:YSGG) laser (2W, 20 Hz, 35.38 J/cm(2), fiber G4 handpiece with 0.2826 mm(2), non-contact mode at a 2 mm distance, 70% air/20% water-G3) or using a chemo-mechanical method (Carisolv-G4). Caries-infected, caries-affected and sound dentines were submitted to a bonding system followed by construction of a resin-based composite crown. Hour-glass shaped samples were obtained and submitted to a micro-tensile bond test. The bond strength data were compared by analysis of variance (ANOVA), complemented by Tukey`s test (P <= 0.05). The samples of sound dentine presented higher bond strengths than did samples of caries-affected dentine, except for the groups treated with the Er,Cr:YSGG laser. The highest bond strengths were observed with the sound dentine treated with burs and Carisolv. The bond strengths to caries-affected dentine were similar in all groups. Additionally, bonding to caries-affected dentine of the Er,Cr:YSGG laser and Carisolv groups was similar to bonding to caries-infected dentine. Thus, caries-affected dentine is not an adequate substrate for adhesion. Moreover, amongst the caries removal methods tested, the Er,Cr:YSGG laser irradiation was the poorest in providing a substrate for bonding with the tested self-etching system.

The ratio of messenger RNA levels of receptor activator of nuclear factor kappa B ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis

skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor KB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA, (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.

Endocytosis of uncleaved tumor necrosis factor-alpha in macrophages

Activated monocytes and macrophages secrete the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) TNF-alpha is produced as a 26 kd transmembrane protein that is cleaved to release a 17 kd soluble protein. TNF-alpha in both forms is biologically active. The intracellular trafficking of membrane-associated TNF-alpha in lipopolysaccharide-activated mouse macrophages was assessed after treatment with the metalloprotease inhibitor BB-3103, which prevents the cleavage of pro-TNF-alpha. Immunoprecipitation and immunofluorescence studies showed sustained expression of cell-associated TNF-alpha in the presence of the inhibitor. Cell immunoreactivity and surface biotinylation revealed that uncleaved TNF-alpha accumulated on the cell surface and was endocytosed, appearing in intracellular vesicles. Perturbation of post-Golgi traffic blocked the surface expression of 26 kd TNF-alpha. Tracking a bolus of TNF-alpha over time in cycloheximide-treated cells confirmed that uncleaved TNF-alpha is first transported to the cell surface and subsequently endocytosed. Vesicular structures immunoreactive for TNF-alpha were identified as endosomes by double labeling. The secretory and membrane-associated endocytic trafficking of TNF-alpha provides a mechanism for modulating the quantity of biologically active 26 kd TNF-alpha expressed on macrophages, allowing regulation of paracrine and autocrine responses.

Total synthesis and absolute stereochemistry of plakortone D

The first total synthesis of plakortone D is described and thereby establishes the structure and absolute stereochemistry of the most biologically active member of the marine-derived plakortone family. The sterically congested bicyclic lactone core results from a Pd(II)-induced hydroxycyclization−carbonylation−lactonization sequence on an enediol whose chirality was installed by AD-technology. Attachment of the side chain, also constructed using AD-methodology, was achieved by using a modified Julia coupling. The described approach enables acquisition of other plakortones and analogues, in the correct (natural) stereochemical series.

Localization of a novel melanoma susceptibility locus to 1p22

Over the past 20 years, the incidence of cutaneous malignant melanoma (CMM) has increased dramatically worldwide. A positive family history of the disease is among the most established risk factors for CMM; it is estimated that 10% of CMM cases result from an inherited predisposition. Although mutations in two genes, CDKN2A and CDK4, have been shown to confer an increased risk of CMM, they account for only 20%-25% of families with multiple cases of CMM. Therefore, to localize additional loci involved in melanoma susceptibility, we have performed a genomewide scan for linkage in 49 Australian pedigrees containing at least three CMM cases, in which CDKN2A and CDK4 involvement has been excluded. The highest two-point parametric LOD score (1.82; recombination fraction [theta] 0.2) was obtained at D1S2726, which maps to the short arm of chromosome 1 (1p22). A parametric LOD score of 4.65 (theta = 0) and a nonparametric LOD score of 4.19 were found at D1S2779 in nine families selected for early age at onset. Additional typing yielded seven adjacent markers with LOD scores 13 in this subset, with the highest parametric LOD score, 4.95 (theta = 0) ( nonparametric LOD score 5.37), at D1S2776. Analysis of 33 additional multiplex families with CMM from several continents provided further evidence for linkage to the 1p22 region, again strongest in families with the earliest mean age at diagnosis. A nonparametric ordered sequential analysis was used, based on the average age at diagnosis in each family. The highest LOD score, 6.43, was obtained at D1S2779 and occurred when the 15 families with the earliest ages at onset were included. These data provide significant evidence of a novel susceptibility gene for CMM located within chromosome band 1p22.

Writing the body of the mother: Narrative moments in Tsushima Yuko, Ariyoshi Sawako and Enchi Fumiko

This discussion argues the transformative potential inherent in the corporeal experience of motherhood as represented in selected textual moments of Japanese narrative. Narratives that address the experiences of the body of the mother are informed and given substance by an intense physicality, and thus have the potential to contest processes of social inscription in addition to suggesting alternative possibilities for all readers, not just those occupying an embodied maternal space. The discussion features brief events from the work of three writers who have written as mothers: Tsushima Y(u)macrko, Ariyoshi Sawako and Enchi Fumiko. In Yama o hashiru onna (1980; translated as Woman Running in the Mountains, 1991), Tsushima Y(u)macrko invites the reader to consider the embodied response to light of Takiko, a young pregnant woman. Emiko, the protagonist of Hishoku (Without Colour, 1967) by Ariyoshi Sawako, is the Japanese wife of an African American and has just given birth to a child. The daughter protagonist in Enchi Fumiko's 'Kami' ('Hair', 1957) operates a hairdressing business that is viable only with her mother's unpaid labour. The narratives are read through a matrix of post-structuralist theories of embodiment, drawing on the work of writers such as Julia Kristeva, Luce Irigaray and Elizabeth Grosz.

Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls

Abnormalities of calcium and vitamin D metabolism in cystic fibrosis (CF) are well documented. We tested the hypothesis that alterations in calcium metabolism are related to vitamin D deficiency, and that bone resorption is increased relative to accretion in patients with CF. Calcitropic hormones, electrolytes, osteocalcin (OC) and bone alkaline phosphatase (BAP), (markers of bone mineralisation), urinary deoxypyridinoline [total (t) Dpd, a marker of bone resorption] and lumbar spine bone mineral density (LS BMD), expressed as a z-score, were measured in 149 (81 M) CF and 141 (61 M) control children aged 5.3-10.99 years, adolescents aged 11-17.99 years and adults aged 18-55.9 years. Data were analysed by multiple regression to adjust for age. In patients, FEV1% predicted and CRP (as disease severity markers), genotype and pancreatic status (PS) were recorded. The distribution of PTH differed between groups (P

A tens??o na defini????o de compet??ncias entre Judici??rio e Executivo: a coleta de lixo

O estudo de caso analisa o fen??meno de judicializa????o de pol??ticas p??blicas, o qual se d?? quando se transfere quest??es de cunho pol??tico, t??picas do Poder Executivo e do Legislativo, para serem analisadas pelo Poder Judici??rio. Considerando-se o extenso leque de direitos sociais, o Poder Judici??rio passa a ser tamb??m demandado em quest??es pol??ticas mais espec??ficas, previstas ou n??o em pol??ticas p??blicas, o que gera in??meras possibilidades de atua????o para esta esfera de poder. O presente caso analisa, portanto, a tens??o na defini????o de compet??ncias entre os Poderes Judici??rio e Executivo, no que se refere ?? coleta de lixo no munic??pio de Cambuquira, Minas Gerais. Ele aborda dois direitos sociais: o direito ?? sa??de e ao meio ambiente saud??vel. O estudo suscita, portanto, o debate sobre a exist??ncia de uma pol??tica p??blica, que passa a ser questionada no Poder Judici??rio, debatendo-se quais seriam os reais limites da democracia

Nota informativa ACI/2014/001: constru????o de um marco anal??tico de avalia????o do projeto de coopera????o t??cnica internacional ???apoio ao desenvolvimento do setor algodoeiro do Cotton-4??? - ENAP/ABC

O texto possui quatro partes. A parte 1, Antecedentes, traz um hist??rico dos trabalhos conjuntos entre ENAP e ABC que justicam a solicita????o de apoio da ENAP para os desenvolvimentos sobre o projeto Cotton-4; a parte 2, A demanda da ABC a ENAP, contextualiza o projeto Cotton 4 e detalha a solicita????o original da ABC; a parte 3, Oportunidades para a ENAP, exp??e como a proposta foi complementada para potencializar outros trabalhos em curso da Escola. Finalmente, a parte 4, Implementa????o de a????es e seus principais resultados, resume os prop??sitos e a estrat??gia de execu????o do termo de coopera????o firmado entre ENAP e ABC

Financiamento da cultura

O Minist??rio da Cultura tem por atribui????o formular e implementar a pol??tica nacional de desenvolvimento da cultura, estimular, acolher e apoiar as iniciativas destinadas a desenvolver e fortalecer as atividades culturais no Brasil, nas suas diversas e variadas formas de manifesta????o. Um dos instrumentos da pol??tica de incentivo ?? cultura ?? a Lei Rouanet, que permite que parte do Imposto de Renda da Pessoa Jur??dica seja deduzido a t??tulo de apoio ??s atividades culturais. A Lei Rouanet (Lei 8313/91) foi formulada num momento em que a cultura brasileira passava por uma fase de descr??dito junto aos governantes. No seu conjunto, procurou corrigir falhas e distor????es da legisla????o anterior, de modo a estabelecer maior transpar??ncia no relacionamento entre o produtor cultural e o empres??rio, adequando-o ??s exig??ncias fiscais vigentes. Entretanto, os resultados n??o foram satisfat??rios. Buscando solucionar o problema, o Minist??rio da Cultura adotou quatro conjuntos de medidas. A iniciativa obteve aumento do n??mero de projetos apresentados, aprovados e incentivados, comprovando a efic??cia das medidas adotadas. Come??aram a surgir projetos das regi??es Norte e Nordeste e do interior dos estados, indicando o impacto desconcentrador das medidas

O aperfei??oamento dos servidores do Estado

A preocupa????o com a qualifica????o do servidor p??blico n??o ?? um tema recente. A primeira experi??ncia de profissionaliza????o do servi??o p??blico remonta ?? cria????o do Departamento Administrativo do Servi??o P??blico (Dasp), em 1938. A exist??ncia do ??rg??o permitiu que fosse iniciada reflex??o sobre a burocracia de Estado: seu dimensionamento e necessidade de forma????o e capacita????o, entre outras quest??es. O texto a seguir foi produzido por um dos quadros t??cnicos do Dasp, em 1942 ??? h?? cerca de 70 anos. Naquele per??odo j?? existia preocupa????o com o aperfei??oamento constante do servidor. O autor argumenta n??o somente em favor desse aprendizado constante, mas tamb??m pela necessidade de um bom curso de forma????o inicial para as carreiras, o que ??? segundo ele ??? n??o era comum naquela ??poca. Conforme o autor, ???de nada adianta ensinar processos novos a quem ainda n??o conhece os m??todos velhos???. Algu??m discordaria? Entretanto, a busca pela novidade, pelo guru da moda (aquele que tem a resposta para os problemas) ?? uma constante no cen??rio dos dirigentes. N??o seria isso resultado de um problema de forma????o de base? Afinal, a administra????o tem alguns conjuntos de t??cnicas que fazem dela uma ci??ncia. Ser?? que nossos gestores as conhecem de verdade? E se as conhecem, sabem aplic??-las? Entre o conhecimento te??rico e pr??tico existe uma grande dist??ncia. Diante de um problema grave que persiste h?? bastante tempo numa institui????o e que requer esfor??o de aprendizado por parte do gestor ??? para apreender, processar e propor uma solu????o ???, muitas vezes se escolhe um atalho: a solu????o miraculosa que maquia, mas n??o resolve. Mas essa j?? ?? outra hist??ria.