Unfavorable Outcomes During Treatment Of Multiple Sclerosis With High Doses Of Vitamin D.

346

The Effects Of High Doses Of Nandrolone Decanoate And Exercise On Prostate Microvasculature Of Adult And Older Rats.

The present study aimed to investigate the effects of the interaction between the abusive use of nandrolone decanoate (ND) and physical activity on the prostate structure of adult and older rats. We evaluated whether the use of ND, associated or not with physical exercise during the post-pubertal stage, interferes with the morphophysiology of the prostate. Fifty-six male Sprague-Dawley rats were divided into eight groups. The animals were treated for eight weeks and divided into sedentary and trained groups, with or without ND use. Four groups were sacrificed 48 h after the end of the eight week experiment (adult groups), and four other groups were sacrificed at 300 days of age (older groups). The prostate was collected and processed for stereological and histopathological analysis and for the expression of AQP1 and VEGF by the Western blotting technique. Both ND and physical activity altered the ventral prostate structure of the rats; the AQP1 and VEGF expression increased in young animals subjected to physical exercise. Thus, it was concluded that the use of ND, associated or not with exercise during the post-pubertal stage, interferes with the morphophysiology of the prostate.

Efeito de baixas doses de radiação X em feridas suturadas e não suturadas - estudo experimental em ratos

The present work evaluated the effect of low doses of X-irradiation on the repairing process of sutured and nonsutured skin wounds in rats. For that, rats underwent a surgical proceedure, in which a 20 x 5-millimeter rectangular wound approximately 2-millimeter-deep was made in the dorsal region of each animal, and were divided in four groups: nonirradiated nonsutured; irradiated nonsutured ; nonirradiated sutured and irradiated sutured. The animals under irradiation were protected, during exposure, with a 2-millimeter-thick lead apron in such a way that only the incision was irradiated. Each animal was submitted to 18 seconds of exposure, undergoing a total of 7.4 rads. The evaluation of the effects of X-rays on the repairing process was carried out through microscopic observation by means of hematoxylin-eosin staining for morphological evaluation, and silver impregnation under polarized light for the observation of collagen synthesis. The results have shown that X-irradiation has caused delay in the repairing process, but it did not stop its development. The irradiated nonsutured group was considered to show the greater delay when compared with the other groups.

Cumulative doses of radioiodine in the treatment of differentiated thyroid carcinoma: knowing when to stop

OBJECTIVE: Evaluate the efficacy of cumulative doses (CDs) of 131I-iodide therapy (RIT) in differentiated thyroid cancer (DTC). SUBJECTS AND METHODS: The probability of progressive disease according to CDs was evaluated in patients < 45 years old and > 45 years old and correlated to tumor-node-metastasis (TNM), thyroglobulin values, histological types and variants, age, and zduration of the disease. RESULTS: At the end of a follow-up period of 69 ± 56 months, 85 out of 150 DTC patients submitted to fixed doses RIT had no evidence of disease, 47 had stable disease and 18 had progressive disease. Higher CDs were used in the more aggressive variants (p < 0.0001), higher TNM stages (p < 0.0001), and follicular carcinomas (p = 0.0034). Probability of disease progression was higher with CDs > 600 mCi in patients > 45 years old and with CDs > 800 mCi in patients < 45 years. CONCLUSION: Although some patients may still respond to high CDs, the impact of further RIT should be carefully evaluated and other treatment strategies may be warranted.

Produção de massa seca, relação folha/colmo e alguns índices de crescimento do Brachiaria brizantha cv. Xaraés cultivado com a combinação de doses de nitrogênio e potássio

Objetivou-se avaliar a produção de massa seca das folhas, a relação folha/colmo e alguns índices de crescimento do capim-xaraés submetido a doses de nitrogênio (N) e potássio (K). O experimento foi conduzido em casa-de-vegetação no período de novembro/2004 a fevereiro/2005. Adotou-se esquema fatorial 4 ´ 3, perfazendo 12 combinações, as quais foram distribuídas em delineamento experimental inteiramente casualizado, com quatro repetições, perfazendo um total 48 unidades experimentais. Foram utilizadas quatro doses de N (0, 75, 150 e 225 mg dm-3) e três doses de K (0, 50 e 100 mg dm-3). Verificou-se efeito das doses de N na produção de massa seca das folhas e na produção de massa seca total, em todos os cortes, com maior produção nas doses mais elevadas de N, ao passo que o K influenciou essas variáveis apenas no segundo corte. A relação folha/colmo, a RAF, a AFE e a RPF somente foram significativas no terceiro corte da planta. Os efeitos das doses de foram decrescentes sobre essas variáveis, enquanto as doses de K agiram de modo antagônico às doses de N sobre a RAF e AFE.

Trypanosoma cruzi benznidazole susceptibility in vitro does not predict the therapeutic outcome of human Chagas disease

Therapeutic failure of benznidazole (BZ) is widely documented in Chagas disease and has been primarily associated with variations in the drug susceptibility of Trypanosoma cruzi strains. In humans, therapeutic success has been assessed by the negativation of anti-T. cruzi antibodies, a process that may take up to 10 years. A protocol for early screening of the drug resistance of infective strains would be valuable for orienting physicians towards alternative therapies, with a combination of existing drugs or new anti-T. cruzi agents. We developed a procedure that couples the isolation of parasites by haemoculture with quantification of BZ susceptibility in the resultant epimastigote forms. BZ activity was standardized with reference strains, which showed IC50 to BZ between 7.6-32 µM. The assay was then applied to isolates from seven chronic patients prior to administration of BZ therapy. The IC50 of the strains varied from 15.6 ± 3-51.4 ± 1 µM. Comparison of BZ susceptibility of the pre-treatment isolates of patients considered cured by several criteria and of non-cured patients indicates that the assay does not predict therapeutic outcome. A two-fold increase in BZ resistance in the post-treatment isolates of two patients was verified. Based on the profile of nine microsatellite loci, sub-population selection in non-cured patients was ruled out.

Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants: mechanisms and implications

The substantial therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetramethyl-1-piperidinyloxy) and related cyclic nitroxides as antioxidants has stimulated innumerous studies of their reactions with reactive oxygen species. In comparison, reactions of nitroxides with nitric oxide-derived oxidants have been less frequently investigated. Nevertheless, this is relevant because tempol has also been shown to protect animals from injuries associated with inflammatory conditions, which are characterized by the increased production of nitric oxide and its derived oxidants. Here, we review recent studies addressing the mechanisms by which cyclic nitroxides attenuate the toxicity of nitric oxidederived oxidants. As an example, we present data showing that tempol protects mice from acetaminophen-induced hepatotoxicity and discuss the possible protection mechanism. In view of the summarized studies, it is proposed that nitroxides attenuate tissue injury under inflammatory conditions mainly because of their ability to react rapidly with nitrogen dioxide and carbonate radical. In the process the nitroxides are oxidized to the corresponding oxammonium cation, which, in turn, can be recycled back to the nitroxides by reacting with upstream species, such as peroxynitrite and hydrogen peroxide, or with cellular reductants. An auxiliary protection mechanism may be down-regulation of inducible nitric oxide synthase expression. The possible therapeutic implications of these mechanisms are addressed.

Epidemiologia da Leishmaniose Tegumentar e descrição das populações de flebotomíneos no município de Acrelândia, Acre, Brasil

São apresentadas neste artigo a distribuição da leishmaniose tegumentar (LT) e descrição das populações de flebotomíneos em Acrelândia, Acre. Os dados epidemiológicos foram obtidos a partir de fichas de notificação de casos ocorridos entre 2001 e 2004, e os dados entomológicos são provenientes de capturas com armadilhas luminosas efetuadas entre 2004 e 2005 na zona rural de Acrelândia. Ocorreram 82 novos casos de LT, com idade entre 2 e 69 anos, sendo 75,6% em homens e 83,9% na zona rural. Predominou a LT com lesões únicas (78%). A microscopia direta da lesão, intradermorreação de Montenegro e biópsia apresentaram positividade de 100%, 98% e 79,5%, respectivamente. A resposta ao tratamento farmacológico foi bem sucedida em 71,6% dos casos; a falência terapêutica foi maior em pacientes com diagnóstico exclusivamente clínico (41,2%) e nos que receberam dose diária inadequada de antimonial pentavalente (64,3%). Foram coletados 40 espécimes de flebotomíneos em propriedades rurais com casos de LT (3 gêneros, 14 espécies), sendo 3 espécies conhecidas como vetoras ou possíveis vetoras de Leishmania: Nyssomyia antunesi predominou no peridomicílio (59,1%) e em margens de matas; Nyssomyia whitmani foi freqüente no peridomicílio (15%) e a única espécie encontrada no intradomicílio, e Trichophoromyia ubiquitalis foi capturada no peridomicílio. O uso de dados epidemiológicos existentes no serviço de saúde de Acrelândia, embora com várias limitações, permitiu avaliar a eficácia do diagnóstico e o tratamento empregados no município, enquanto os dados entomológicos coletados podem orientar estudos mais amplos visando identificar os vetores e espécies circulantes na região.

Effect of n-3 polyunsaturated fatty acids on oxidative stress in rats supplemented with different doses of fish oil

The diet and plasma lipid patterns associated with lipid oxidation susceptibility in rats fed different doses of polyunsaturated fatty acids (n-3 PUFA) from fish oil were evaluated. Wistar rats were assigned into three groups and received diets containing 8% soybean oil (SOY), 4% soybean oil + 4% fish oil (SOY-FISH) and 8% fish oil (FISH) for 21 days. Linoleic, oleic and ?-linolenic acids in SOY diets were substituted by myristic, palmitic, palmitoleic, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in SOY-FISH and FISH diets reducing the n-6/n-3 ratio and increasing the peroxidability index (PI). Increased dietary EPA and DHA were observed in SOY-FISH and FISH plasma at the expense of linoleic and arachidonic acid levels. Saturated fatty acids, which were significantly different between the three diets (P < 0.01), were found at the same concentration in the plasma (P = 0.23). No changes were observed in oxidative stress as measured by the concentration of thiobarbituric acid reactive substances (TBARS) expressed in brain homogenates. However, TBARS concentration in the plasma of the SOY-FISH group was higher than the other two groups (P = 0.02). The major differences between these three groups were the n-3 PUFA content (0.4, 1.8 and 3.2 g/100 g diet) and the saturates/polyunsaturates ratio (0.3, 0.5 and 0.8) for SOY, SOY-FISH, and FISH groups, respectively. Thus, n-3 PUFA intake from fish oil only when followed by a decrease in saturated/polyunsaturated fatty acids ratio increased oxidative susceptibility in rats measured by plasma TBARS concentration

Leukotriene B(4)-loaded microspheres: a new therapeutic strategy to modulate cell activation

Background: Leukotriene B(4) (LTB(4)) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB(4) released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB(4)-loaded MS. Results: In the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB(4)-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emigration besides significant decreases in the leukocyte rolling velocity. LTB(4)-loaded MS also increase peroxisome proliferator-activated receptor-alpha (PPAR alpha) expression by murine peritoneal macrophages and stimulate them to generate nitrite levels. Monocyte chemoattractant protein-I (MCP-I) and nitric oxide (NO) productions were also increased when human umbilical vein and artery endothelial cells (HUVECs and HUAECs, respectively) were stimulated with LTB(4)-loaded MS. Conclusion: LTB(4)-loaded MS preserve the biological activity of the encapsulated mediator indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.

Helminth Coinfection Does Not Affect Therapeutic Effect of a DNA Vaccine in Mice Harboring Tuberculosis

Background: Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65. Methodology/Principal Findings: Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-gamma production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-beta and IL-10 production, which could be associated with long-term protection. Conclusions/Significance: We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections.

Effect of GaAlAs Laser Irradiation on the Epiphyseal Cartilage of Rats

Objective: To study the effect of an 830-nm gallium-aluminum-arsenic (GaAlAs) diode laser at two different energy densities (5 and 15 J/cm(2)) on the epiphyseal cartilage of rats by evaluating bone length and the number of chondrocytes and thickness of each zone of the epiphyseal cartilage. Background Data: Few studies have been conducted on the effects of low-level laser therapy on the epiphyseal cartilage at different irradiation doses. Materials and Methods: A total of 30 male Wistar rats with 23 days of age and weighing 90 g on average were randomly divided into 3 groups: control group (CG, no stimulation), G5 group (energy density, 5 J/cm(2)), and G15 group (energy density, 15 J/cm(2)). Laser treatment sessions were administered every other day for a total of 10 sessions. The animals were killed 24 h after the last treatment session. Histological slides of the epiphyseal cartilage were stained with hematoxylin-eosin (HE), photographed with a Zeiss photomicroscope, and subjected to histometric and histological analyses. Statistical analysis was performed using one-way analysis of variance followed by Tukey's post hoc test. All statistical tests were performed at a significance level of 0.05. Results: Histological analysis and x-ray radiographs revealed an increase in thickness of the epiphyseal cartilage and in the number of chondrocytes in the G5 and G15 groups. Conclusion: The 830-nm GaAlAs diode laser, within the parameters used in this study, induced changes in the thickness of the epiphyseal cartilage and increased the number of chondrocytes, but this was not sufficient to induce changes in bone length.

Myeloid differentiation factor 88 is required for resistance to Neospora caninum infection

Neospora caninum is an intracellular parasite that causes major economic impact on cattle raising farms, and infects a wide range of warm-blooded hosts worldwide. Innate immune mechanisms that lead to protection against this parasite are still unknown. In order to investigate whether myeloid differentiation factor 88 (MyD88) is required for resistance against N. caninum, genetically deficient mice (MyD88(-/-)) and wild type littermates were infected with live tachyzoites and the resistance to infection was evaluated. We found that sub-lethal tachyzoite doses induced acute mortality of MyD88(-/-) mice, which succumbed to infection due to uncontrolled parasite replication. Higher parasitism in MyD88(-/-) mice was associated with the lack of IL-12 production by dendritic cells, delayed IFN-gamma responses by NKT, CD4(+) and CD8(+) T lymphocytes, and production of high levels of IL-10. MyD88(-/-) mice replenished with IL-12 and IFN-gamma abolished susceptibility as the animals survived throughout the experimental period. We conclude that protective IFN-gamma-mediated immunity to N. caninum is dependent on initial MyD88 signaling, in a mechanism triggered by production of IL-12 by dendritic cells. Further knowledge on Toll-like receptor recognition of N. caninum antigens is encouraged, since it could generate new prophylactic and therapeutic tools to control parasite burden.

Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B(1)

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

Phytomass production and nitrogen accumulation in maize cultivated with different doses of (15)N-urea

This work aimed to study the possible alterations in production, accumulation of the vegetative phytomass and nitrogen efficiency use of the maize crop, in different doses of N applied in the fertilization, by using the technique of isotopic dilution of (15)N. The completely randomized block experimental design was adopted, with 5 treatments and 4 replicates. The following treatments were constituted in the doses in covering: 0, 50, 100, 150 and 200 kg ha(-1) of N, with fertilization of N-urea, respectively. Comparisons among the treatments had been run for crop productivity; nitrogen accumulation for the plant, and use of the nitrogen of the urea-(15)N for the crop. The increase of the dose of N-fertilizer resulted in increase of the dry matter mass, of the dry matter yield crop tax, of the productivity and accumulation of N in the maize plants.