180 research outputs found
GAMMA-ORYZANOL HAS AN EQUIVALENT EFFICACY AS A LIPID-LOWERING AGENT COMPARED TO FIBRATE AND STATIN IN TWO DYSLIPIDEMIA MICE MODELS
Objective: A substantial fraction of the population is intolerant or does not respond well to the recommended treatments for dyslipidemia. The purpose of this study was to evaluate the efficacy ofgamma-oryzanol (ĂÂł-ORZ) treatment in acute and long-term mouse experimental models of dyslipidemia in comparison toGemfibrozil and Simvastatin.
Methods: For the acute dyslipidemia-induced model, dyslipidemia was induced in 40 mice using a single intra-peritoneal administration of Triton WR-1339. For the long-termmodel, dyslipidemia was induced in 24 mice using a hypercholesterolemic diet over 14 days. Thereafter, animals were divided into different groups of treatment,and orally received treatments with gamma-oryzanol (5, 25, 50mg. kg-1), gemfibrozil or simvastatin. For biochemical analysis, glucose, total cholesterol and triacylglycerols were measured. Body weight and net food intake was registered weekly, and urea, creatinine, AST and ALT levels were evaluated. The data were analyzed by analysis of variance (ANOVA), followed by the Student-Newman-Keuls method,and p value of less than 0.05 was considered significant.
Results: Only the highest dose of ĂÂł-ORZ exhibited significant protective effects. Gamma-oryzanol andGemfibrozil treatments reduced total cholesterol and triacylglycerols levels in a similar manner in the acute model. In the second model, ĂÂł-ORZ and simvastatin treatments reduced glucose and total cholesterol levels in the same way. In addition, the administration ofĂÂł-ORZ did not cause any adverse events, or significantly altered hepatic enzymes levels, plasmatic urea or creatinine concentrations.
Conclusion: The results of this study suggest that gamma-oryzanol acts as a potential lipid-lowering agent, reducing triglycerides and total cholesterol in dyslipidemia-induced models
In vivo and in vitro effects of RAD001 on bladder cancer
Objective: To evaluate the influence of Everolimus (RAD001) on chemically induced urothelial lesions in mice and its influence on in vitro human bladder cancer cell lines.
Methods: ICR male mice were given N-butyl-N-(4-hydroxybutyl) nitrosamine in drinking water for a period of 12 weeks. Subsequently,
RAD001 was administered via oral gavage, for 6 weeks. At the end of the experiment, all the animals were sacrificed and tumor development was determined by means of histopathologic evaluation; mammalian target of rapamycin (mTOR) expressivity was evaluated by immunohistochemistry. Three human bladder cancer cell lines (T24, HT1376, and 5637) were treated using a range of RAD001 concentrations. MTT assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and flow cytometry were used to assess cell proliferation, apoptosis index, and cell cycle analysis, respectively. Immunoblotting analysis of 3 cell line extracts using mTOR
and Akt antibodies was performed in order to study the expression of Akt and mTOR proteins and their phosphorylated forms.
Results: The incidence of urothelial lesions in animals treated with RAD001 was similar to those animals not treated. RAD001 did not
block T24 and HT1376 cell proliferation or induce apoptosis. A reduction in cell proliferation rate and therefore G0/G1 phase arrest, as well as a statistically significant induction of apoptosis (P 0.001), was only observed in the 5637 cell line. Conclusion: RAD001 seems not to have a significant effect on chemically induced murine bladder tumors. The effect of RAD001 on tumor proliferation and apoptosis was achieved only in superficial derived bladder cancer cell line, no effect was observed in invasive cell lines
One More Piece in the VACV Ecological Puzzle: Could Peridomestic Rodents Be the Link between Wildlife and Bovine Vaccinia Outbreaks in Brazil?
BACKGROUND: Despite the fact that smallpox eradication was declared by the World Health Organization (WHO) in 1980, other poxviruses have emerged and re-emerged, with significant public health and economic impacts. Vaccinia virus (VACV), a poxvirus used during the WHO smallpox vaccination campaign, has been involved in zoonotic infections in Brazilian rural areas (Bovine Vaccinia outbreaks - BV), affecting dairy cattle and milkers. Little is known about VACV's natural hosts and its epidemiological and ecological characteristics. Although VACV was isolated and/or serologically detected in Brazilian wild animals, the link between wildlife and farms has not yet been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we describe for the first time, to our knowledge, the isolation of a VACV (Mariana virus - MARV) from a mouse during a BV outbreak. Genetic data, in association with biological assays, showed that this isolate was the same etiological agent causing exanthematic lesions observed in the cattle and human inhabitants of a particular BV-affected area. Phylogenetic analysis grouped MARV with other VACV isolated during BV outbreaks. CONCLUSION/SIGNIFICANCE: These data provide new biological and epidemiological information on VACV and lead to an interesting question: could peridomestic rodents be the link between wildlife and BV outbreaks
Influence of Ecto-Nucleoside Triphosphate Diphosphohydrolase Activity on Trypanosoma cruzi Infectivity and Virulence
The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, an endemic zoonosis present in some countries of South and Central Americas. The World Health Organization estimates that 100 million people are at risk of acquiring this disease. The infection affects mainly muscle tissues in the heart and digestive tract. There are no vaccines or effective treatment, especially in the chronic phase when most patients are diagnosed, which makes a strong case for the development of new drugs to treat the disease. In this work we evaluate a family of proteins called Ecto-Nucleoside-Triphosphate-Diphosphohydrolase (Ecto-NTPDase) as new chemotherapy target to block T. cruzi infection in mammalian cells and in mice. We have used inhibitors and antibodies against this protein and demonstrated that T. cruzi Ecto-NTPDases act as facilitators of infection in mammalian cells and virulence factors in mice model. Two of the drugs used in this study (Suramin and Gadolinium) are currently used for other diseases in humans, supporting the possibility of their use in the treatment of Chagas disease
Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory
The Pierre Auger Collaboration has reported evidence for anisotropy in the
distribution of arrival directions of the cosmic rays with energies
eV. These show a correlation with the distribution
of nearby extragalactic objects, including an apparent excess around the
direction of Centaurus A. If the particles responsible for these excesses at
are heavy nuclei with charge , the proton component of the
sources should lead to excesses in the same regions at energies . We here
report the lack of anisotropies in these directions at energies above
(for illustrative values of ). If the anisotropies
above are due to nuclei with charge , and under reasonable
assumptions about the acceleration process, these observations imply stringent
constraints on the allowed proton fraction at the lower energies
Biological activity and persistence of pirimiphos-methyl applied to maize grain at different temperatures
Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine
Background: The lack of sensitive and specific biomarkers for the early detection of prostate cancer (PCa) is a major hurdle to improve patient management. Methods: A metabolomics approach based on GC-MS was used to investigate the performance of volatile organic compounds (VOCs) in general and, more specifically, volatile carbonyl compounds (VCCs) present in urine as potential markers for PCa detection. Results: Results showed that PCa patients (n = 40) can be differentiated from cancer-free subjects (n = 42) based on their urinary volatile profile in both VOCs and VCCs models, unveiling significant differences in the levels of several metabolites. The models constructed were further validated using an external validation set (n = 18 PCa and n = 18 controls) to evaluate sensitivity, specificity and accuracy of the urinary volatile profile to discriminate PCa from controls. The VOCs model disclosed 78% sensitivity, 94% specificity and 86% accuracy, whereas the VCCs model achieved the same sensitivity, a specificity of 100% and an accuracy of 89%. Our findings unveil a panel of 6 volatile compounds significantly altered in PCa patients' urine samples that was able to identify PCa, with a sensitivity of 89%, specificity of 83%, and accuracy of 86%. Conclusions: It is disclosed a biomarker panel with potential to be used as a non-invasive diagnostic tool for PCa.info:eu-repo/semantics/publishedVersio
Inflammatory responses and intestinal injury development during acute Trypanosoma cruzi infection are associated with the parasite load
Composição quĂmica, compostos bioativos e dissimilaridade genĂ©tica entre cultivares de amoreira (Rubus spp.) cultivadas no Sul de Minas Gerais
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