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21.
Bifunctional alkylating agents are used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. Nitrogen mustards are commonly used chemotherapeutic agents that can bind mono- or bifunctionally to guanines in DNA. Mustard HN1 is considered a monofunctional analog of bifunctional mustard HN2 (mechlorethamine). Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) or base excision repair (BER) were submitted to increasing concentrations of HN2 or HN1, and the results revealed that damage induced by each chemical demands different DNA repair pathways. Damage induced by HN2 demands the activity of NER with a minor requirement of the BER pathway, while HN1 damage repair depends on BER action, without any requirement of NER function. Taken together, our data suggest that HN1 and HN2 seem to induce different types of damage, since their repair depends on distinct pathways in E. coli. 相似文献
22.
Harikrishnan Parameswaran Arnab Majumdar Satoru Ito Adriano M Alencar Béla Suki 《Journal of applied physiology》2006,100(1):186-193
The mean linear intercept (L(m)) can be used to estimate the surface area for gas exchange in the lung. However, in recent years, it is most commonly used as an index for characterizing the enlargement of airspaces in emphysema and the associated severity of structural destruction in the lung. Specifically, an increase in L(m) is thought to result from an increase in airspace sizes. In this paper, we examined how accurately L(m) measures the linear dimensions of airspaces from histological sections and a variety of computer-generated test images. To this end, we developed an automated method for measuring linear intercepts from digitized images of tissue sections and calculate L(m) as their mean. We examined how the shape of airspaces and the variability of their sizes influence L(m) as well as the distribution of linear intercepts. We found that, for a relatively homogeneous enlargement of airspaces, L(m) was a reliable index for detecting emphysema. However, in the presence of spatial heterogeneities with a large variability of airspace sizes, L(m) did not significantly increase and sometimes even decreased compared with its value in normal tissue. We also developed an automated method for measuring the area and computed an equivalent diameter of each individual airspace that is independent of shape. Finally, we introduced new indexes based on the moments of diameter that we found to be more reliable than L(m) to characterize airspace enlargement in the presence of heterogeneities. 相似文献
23.
Neves RH Alencar AC Aguila MB Mandarim-de-Lacerda CA Machado-Silva JR Gomes DC 《Memórias do Instituto Oswaldo Cruz》2006,101(Z1):253-260
High-fat diets induce weight gain and fatty liver in wild-type mice. Schistosomiasis mansoni infection also promotes hepatic injury. This study was designed to quantify hepatic alterations in schistosomiasis mansoni-infected mice fed a high fat-rich chow compared to mice fed a standard rodent chow, using stereology. Female SW mice fed each either high-fat diet (29% lipids) or standard chow (12% lipids) over 8 months, and then were infected with Schistosoma mansoni cercariae. Four experimental groups were studied: infected mice fed a high-fat diet (IHFC) or standard chow (ISC), uninfected mice fed a high-fat diet (HFC) or standard chow (SC). Mice were sacrificed during early infection (9 weeks from exposure). The following hepatic biometry and the stereology parameters were determined: volume density (hepatocytes [h], sinusoids [s], steatosis [st] and hepatic fibrosis [hf]); numerical density (hepatocyte nuclei - Nv[h]); absolute number of total hepatocyte N[h], normal hepatocyte N[nh], and binucleated hepatocyte N[bh], percentage of normal hepatocyte P[nh] and binucleated hepatocyte P[bh]. IHFC and HFC groups exhibited TC, HDL-C, LDL-C, and body mass significantly greater (p < 0.05) than control group. No significant differences were found regards liver volume (p = 0.07). Significant differences were observed regards P[nh] (p = 0.0045), P[bh] (p = 0.0045), Nv[h] (p = 0.0006), N[h] (p = 0.0125), N[bh] (p = 0.0164) and N[nh] (p = 0.0078). IHFC mice group presented 29% of binucleated hepatocytes compared to HFC group (19%), ISC group (17%) and SC (6%). Volume density was significantly different between groups: Vv[h] (p = 0.0052), Vv[s] (p = 0.0025), Vv[st] (p = 0.0004), and Vv[hf] (p = 0.0007). In conclusion, schistosomiasis mansoni infection with concurrent high-fat diet promotes intensive quantitative changes in hepatic structure, contributing to an increasing on hepatic regeneration. 相似文献
24.
M Imboden A Nieters AJ Bircher M Brutsche N Becker M Wjst U Ackermann-Liebrich W Berger NM Probst-Hensch 《Clinical and molecular allergy : CMA》2006,4(1):1-9
Background
Avoidance of allergens is still recommended as the first and best way to prevent allergic illnesses and their comorbid diseases. Despite a variety of attempts there has been very limited success in the area of environmental control of allergic disease. Our objective was to identify a non-invasive, non-pharmacological method to reduce indoor allergen loads in atopic persons' homes and public environments. We employed a novel in vivo approach to examine the possibility of using aluminum sulfate to control environmental allergens.Methods
Fifty skin test reactive patients were simultaneously skin tested with conventional test materials and the actions of the protein/glycoprotein modifier, aluminum sulfate. Common allergens, dog, cat, dust mite, Alternaria, and cockroach were used in the study.Results
Skin test reactivity was significantly reduced by the modifier aluminum sulfate. Our studies demonstrate that the effects of histamine were not affected by the presence of aluminum sulfate. In fact, skin test reactivity was reduced independent of whether aluminum sulfate was present in the allergen test material or removed prior to testing, indicating that the allergens had in some way been inactivated.Conclusion
Aluminum sulfate was found to reduce the in vivo allergic reaction cascade induced by skin testing with common allergens. The exact mechanism is not clear but appears to involve the alteration of IgE-binding epitopes on the allergen. Our results indicate that it may be possible to diminish the allergenicity of an environment by application of the active agent aluminum sulfate, thus producing environmental control without complete removal of the allergen. 相似文献25.
Fredy D.A. Silva Ilka M. Vasconcelos Marina D.P. Lobo Patrícia G. de Castro Vladimir G. Magalhães Cléverson D.T. de Freitas Célia R.R.S. Carlini Paulo M. Pinto Leila M. Beltramini José H.A. Filho Eduardo B. Barros Luciana M.R. Alencar Thalles B. Grangeiro José T.A. Oliveira 《Biochimica et Biophysica Acta (BBA)/General Subjects》2012
Background
Peroxiredoxins have diverse functions in cellular defense-signaling pathways. 2-Cys-peroxiredoxins (2-Cys-Prx) reduce H2O2 and alkyl-hydroperoxide. This study describes the purification and characterization of a genuine 2-Cys-Prx from Vigna unguiculata (Vu-2-Cys-Prx).Methods
Vu-2-Cys-Prx was purified from leaves by ammonium sulfate fractionation, chitin affinity and ion exchange chromatography.Results
Vu-2-Cys-Prx reduces H2O2 using NADPH and DTT. Vu-2-Cys-Prx is a 44 kDa (SDS-PAGE)/46 kDa (exclusion chromatography) protein that appears as a 22 kDa molecule under reducing conditions, indicating that it is a homodimer linked intermolecularly by disulfide bonds and has a pI range of 4.56–4.72; its NH2-terminal sequence was similar to 2-Cys-Prx from Phaseolus vulgaris (96%) and Populus tricocarpa (96%). Analysis by ESI-Q-TOF MS/MS showed a molecular mass/pI of 28.622 kDa/5.18. Vu-2-Cys-Prx has 8% α-helix, 39% β-sheet, 22% of turns and 31% of unordered forms. Vu-2-Cys-Prx was heat stable, has optimal activity at pH 7.0, and prevented plasmid DNA degradation. Atomic force microscopy shows that Vu-2-Cys-Prx oligomerized in decamers which might be associated with its molecular chaperone activity that prevented denaturation of insulin and citrate synthase. Its cDNA analysis showed that the redox-active Cys52 residue and the amino acids Pro45, Thr49 and Arg128 are conserved as in other 2-Cys-Prx.General significance
The biochemical and molecular features of Vu-2-Cys-Prx are similar to other members of 2-Cys-Prx family. To date, only one publication reported on the purification of native 2-Cys-Prx from leaves and the subsequent analysis by N-terminal Edman sequencing, which is crucial for construction of stromal recombinant 2-Cys-Prx proteins. 相似文献26.
Carvalho Barbosa Rde C Menezes DC Freire TF Sales DC Alencar VH Rabenhorst SH 《Molecular biology reports》2012,39(4):4899-4907
Polymorphisms in genes involved in folate metabolism have been shown to be implicated in breast cancer risk but with contradictory
results. In this case–control study, we investigated the association between MTHFR C677T and A1298C, TYMS 5′-UTR, MTR A2756G and cSHMT C1420T and also the folate carrier (RFC1 G80A) and breast cancer risk in a northeastern Brazilian population. The study included 183 women diagnosed with breast cancer
and 183 controls volunteers without any history of cancer. Also a significant number of healthy individuals were included
for allelic frequency in the population studied. Risk of breast cancer was estimated by conditional logistic regression. An
association with risk was found for women carrying the MTR A2756G polymorphic allele (AG, P = 0.0036; AG/GG, P = 0.0040), and a protective effect in carriers of the RFC1 G80A polymorphic allele (GA, P = 0.0015; AA, P = 0.0042). Stratifying the data by age (cutoff point of 50 years old), different distributions were observed for breast cancer
risk. For women ≤50 years, the risk observed in the presence of the polymorphic allele MTR 2756 (AG/GG) in the general analysis was, restricted to this age group (P = 0.0118). Conversely, for women over 50, the risk of breast cancer development was statistically associated with the MTHFR 677CT genotype, but especially significant was risk associated with the presence of the polymorphic allele of cSHMT C1420T (P = 0.0120) and the protective effect associated with the RFC1 G80A polymorphism allele (P = 0.0021), was restrict to this age group. These data indicate that the cutoff age used (50 years old) was appropriate, since
it was able to discriminate risk in each age group in the population studied and also to point to the importance of age in
the analyses of cancer-associated polymorphisms. 相似文献
27.
Draulio C. SilvaAna Lucia P. Freitas Francisco Clark N. BarrosKézia O.A.L. Lins Ana Paula N.N. AlvesNylane M.N. Alencar Ingrid S.T. de FigueiredoCláudia Pessoa Manoel O. de MoraesLetícia V. Costa-Lotufo Judith P.A. FeitosaJeanny S. Maciel Regina C.M. de Paula 《Carbohydrate polymers》2012,87(1):139-145
A hot water-extracted polysaccharide fraction (PFCM) of Passiflora edulis was characterized by microanalysis, infrared spectroscopy, NMR and high performance size-exclusion chromatography. The major component in PFCM is (1 → 4) linked galacturonic acid (esterified and unesterified). Neutral sugars such as arabinose, glucose, rhamnose, mannose, and fucose were also present. Traces of xylose and ribose were detected. The PFCM sample had a similar molar mass to that of pectin extracted from P. edulis under acidic conditions. Sarcoma 180 tumors treated with PFCM showed a growth inhibition ratio ranging from 40.59% to 48.73% depending on the dosage and type of PFCM administration (oral or intraperitoneal). Toxicological analysis shows that PFCM increases the cell types involved in primary defense mechanisms and no significant changes in the biochemical parameters and organs (e.g., kidney and liver) were observed. However, the use of PFCM treatment increased the spleen weight when compared with the use of 5-fluorouracil. 相似文献
28.
Steve Horvath Abu NM Nazmul-Hossain Rodney PE Pollard Frans GM Kroese Arjan Vissink Cees GM Kallenberg Fred KL Spijkervet Hendrika Bootsma Sara A Michie Sven U Gorr Ammon B Peck Chaochao Cai Hui Zhou David TW Wong 《Arthritis research & therapy》2012,14(6):1-13
Bone tissue has an exceptional quality to regenerate to native tissue in response to injury. However, the fracture repair process requires mechanical stability or a viable biological microenvironment or both to ensure successful healing to native tissue. An improved understanding of the molecular and cellular events that occur during bone repair and remodeling has led to the development of biologic agents that can augment the biological microenvironment and enhance bone repair. Orthobiologics, including stem cells, osteoinductive growth factors, osteoconductive matrices, and anabolic agents, are available clinically for accelerating fracture repair and treatment of compromised bone repair situations like delayed unions and nonunions. Preclinical and clinical studies using biologic agents like recombinant bone morphogenetic proteins have demonstrated an efficacy similar or better than that of autologous bone graft in acute fracture healing. A lack of standardized outcome measures for comparison of biologic agents in clinical fracture repair trials, frequent off-label use, and a limited understanding of the biological activity of these agents at the bone repair site have limited their efficacy in clinical applications. 相似文献
29.
30.
José Ronnie Vasconcelos Oscar Bru?a–Romero Adriano F. Araújo Mariana R. Dominguez Jonatan Ersching Bruna C. G. de Alencar Alexandre V. Machado Ricardo T. Gazzinelli Karina R. Bortoluci Gustavo P. Amarante-Mendes Marcela F. Lopes Mauricio M. Rodrigues 《PLoS pathogens》2012,8(5)
MHC class Ia-restricted CD8+ T cells are important mediators of the adaptive immune response against infections caused by intracellular microorganisms. Whereas antigen-specific effector CD8+ T cells can clear infection caused by intracellular pathogens, in some circumstances, the immune response is suboptimal and the microorganisms survive, causing host death or chronic infection. Here, we explored the cellular and molecular mechanisms that could explain why CD8+ T cell-mediated immunity during infection with the human protozoan parasite Trypanosoma cruzi is not optimal. For that purpose, we compared the CD8+ T-cell mediated immune responses in mice infected with T. cruzi or vaccinated with a recombinant adenovirus expressing an immunodominant parasite antigen. Several functional and phenotypic characteristics of specific CD8+ T cells overlapped. Among few exceptions was an accelerated expansion of the immune response in adenoviral vaccinated mice when compared to infected ones. Also, there was an upregulated expression of the apoptotic-signaling receptor CD95 on the surface of specific T cells from infected mice, which was not observed in the case of adenoviral-vaccinated mice. Most importantly, adenoviral vaccine provided at the time of infection significantly reduced the upregulation of CD95 expression and the proapoptotic phenotype of pathogen-specific CD8+ cells expanded during infection. In parallel, infected adenovirus-vaccinated mice had a stronger CD8 T-cell mediated immune response and survived an otherwise lethal infection. We concluded that a suboptimal CD8+ T-cell response is associated with an upregulation of CD95 expression and a proapoptotic phenotype. Both can be blocked by adenoviral vaccination. 相似文献