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1.
Acta Ortop Bras ; 31(spe2): e262255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37323146

RESUMO

Objective: Investigate the prevalence of postural changes and correlate them with body weight and the weight of schoolchildren's backpacks in a school in the city of São João del-Rei-MG. Material and. Methods: The study is an original type, with a cross-sectional design, where 109 schoolchildren of both sexes and mean age of 13 years were evaluated. The New York scale was used for posture analysis, measuring body weight, height, backpack weight, and Body Mass Index (BMI). The ANOVA statistical test and Pearson's correlation test were used, considering a significance level of 0.05. Results: According to the results, the general average of the scores of postural problems was 68.7 points, with a predominance in the head, spine, hips, trunk, and abdomen. The regions of shoulder, feet, and neck presented mean scores below seven. The mean height was 1.61 m, body weight 56.03 kg, backpack weight 4.49 kg and BMI was 21.51 kg/m. Conclusion: Postural alterations are highly prevalent among the evaluated students. The most affected body segments are the head, spine, hips, trunk, and abdomen. However, this finding was not related to the weight of the backpacks or the students' body weight. However, different parameters must be used to analyze the factors that may be related to such findings, such as ergonomic changes, inadequate habits, growth spurt, among others. Evidence Level III,Cross-sectional Observational Study.


Objetivo: Investigar a prevalência de alterações posturais e correlacionar com o peso corporal e o peso das mochilas dos escolares em uma escola no município de São João del-Rei-MG. Métodos: O estudo é do tipo original, com delineamento transversal onde foram avaliados 109 escolares, com média de idade de 13 anos, de ambos os sexos. A escala de Nova Iorque foi utilizada para análise de postura, medição do peso corporal, altura, peso da mochila e Índice de Massa Corporal (IMC). Foi utilizado o teste estatístico ANOVA e o teste de correlação de Pearson, considerando o nível de significância de 0,05. Resultados: De acordo com os resultados, a média geral dos escores dos problemas posturais foi de 68,7 pontos, com predomínio na região da cabeça, coluna, nos quadris, no tronco, e no abdômen. As regiões dos ombros, pés e pescoço apresentaram médias de escores menores que 7. A média da altura foi de 1,61m, do peso corporal de 56,03kg, do peso das mochilas de 4,49 kg e 21,51 kg/m do IMC. Conclusão: Conclui-se que existe uma alta prevalência de alterações posturais entre os escolares avaliados. Sendo que, os segmentos corporais mais comprometidos são, a cabeça, a coluna vertebral, os quadris, o tronco e o abdômen. No entanto, esse achado não foi relacionado ao peso das mochilas ou ao peso corporal dos escolares. Assim, diferentes parâmetros devem ser utilizados para analisar os fatores que podem estar relacionados a tais achados, como alterações ergonômicas, hábitos inadequados, estirão de crescimento, entre outros. Nível de Evidência III, Estudo Transversal Observacional.

2.
Acta ortop. bras ; 31(spe2): e262255, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1439151

RESUMO

ABSTRACT Objective Investigate the prevalence of postural changes and correlate them with body weight and the weight of schoolchildren's backpacks in a school in the city of São João del-Rei-MG. Material and Methods The study is an original type, with a cross-sectional design, where 109 schoolchildren of both sexes and mean age of 13 years were evaluated. The New York scale was used for posture analysis, measuring body weight, height, backpack weight, and Body Mass Index (BMI). The ANOVA statistical test and Pearson's correlation test were used, considering a significance level of 0.05. Results According to the results, the general average of the scores of postural problems was 68.7 points, with a predominance in the head, spine, hips, trunk, and abdomen. The regions of shoulder, feet, and neck presented mean scores below seven. The mean height was 1.61 m, body weight 56.03 kg, backpack weight 4.49 kg and BMI was 21.51 kg/m. Conclusion Postural alterations are highly prevalent among the evaluated students. The most affected body segments are the head, spine, hips, trunk, and abdomen. However, this finding was not related to the weight of the backpacks or the students' body weight. However, different parameters must be used to analyze the factors that may be related to such findings, such as ergonomic changes, inadequate habits, growth spurt, among others. Evidence Level III,Cross-sectional Observational Study.


RESUMO Objetivo Investigar a prevalência de alterações posturais e correlacionar com o peso corporal e o peso das mochilas dos escolares em uma escola no município de São João del-Rei-MG. Métodos O estudo é do tipo original, com delineamento transversal onde foram avaliados 109 escolares, com média de idade de 13 anos, de ambos os sexos. A escala de Nova Iorque foi utilizada para análise de postura, medição do peso corporal, altura, peso da mochila e Índice de Massa Corporal (IMC). Foi utilizado o teste estatístico ANOVA e o teste de correlação de Pearson, considerando o nível de significância de 0,05. Resultados De acordo com os resultados, a média geral dos escores dos problemas posturais foi de 68,7 pontos, com predomínio na região da cabeça, coluna, nos quadris, no tronco, e no abdômen. As regiões dos ombros, pés e pescoço apresentaram médias de escores menores que 7. A média da altura foi de 1,61m, do peso corporal de 56,03kg, do peso das mochilas de 4,49 kg e 21,51 kg/m do IMC. Conclusão Conclui-se que existe uma alta prevalência de alterações posturais entre os escolares avaliados. Sendo que, os segmentos corporais mais comprometidos são, a cabeça, a coluna vertebral, os quadris, o tronco e o abdômen. No entanto, esse achado não foi relacionado ao peso das mochilas ou ao peso corporal dos escolares. Assim, diferentes parâmetros devem ser utilizados para analisar os fatores que podem estar relacionados a tais achados, como alterações ergonômicas, hábitos inadequados, estirão de crescimento, entre outros. Nível de Evidência III, Estudo Transversal Observacional.

3.
Front Cell Dev Biol ; 9: 633195w, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055812

RESUMO

DNA topoisomerases are enzymes that modulate DNA topology. Among them, topoisomerase 3α is engaged in genomic maintenance acting in DNA replication termination, sister chromatid separation, and dissolution of recombination intermediates. To evaluate the role of this enzyme in Trypanosoma cruzi, the etiologic agent of Chagas disease, a topoisomerase 3α knockout parasite (TcTopo3α KO) was generated, and the parasite growth, as well as its response to several DNA damage agents, were evaluated. There was no growth alteration caused by the TcTopo3α knockout in epimastigote forms, but a higher dormancy rate was observed. TcTopo3α KO trypomastigote forms displayed reduced invasion rates in LLC-MK2 cells when compared with the wild-type lineage. Amastigote proliferation was also compromised in the TcTopo3α KO, and a higher number of dormant cells was observed. Additionally, TcTopo3α KO epimastigotes were not able to recover cell growth after gamma radiation exposure, suggesting the involvement of topoisomerase 3α in homologous recombination. These parasites were also sensitive to drugs that generate replication stress, such as cisplatin (Cis), hydroxyurea (HU), and methyl methanesulfonate (MMS). In response to HU and Cis treatments, TcTopo3α KO parasites showed a slower cell growth and was not able to efficiently repair the DNA damage induced by these genotoxic agents. The cell growth phenotype observed after MMS treatment was similar to that observed after gamma radiation, although there were fewer dormant cells after MMS exposure. TcTopo3α KO parasites showed a population with sub-G1 DNA content and strong γH2A signal 48 h after MMS treatment. So, it is possible that DNA-damaged cell proliferation due to the absence of TcTopo3α leads to cell death. Whole genome sequencing of MMS-treated parasites showed a significant reduction in the content of the multigene families DFG-1 and RHS, and also a possible erosion of the sub-telomeric region from chromosome 22, relative to non-treated knockout parasites. Southern blot experiments suggest telomere shortening, which could indicate genomic instability in TcTopo3α KO cells owing to MMS treatment. Thus, topoisomerase 3α is important for homologous recombination repair and replication stress in T. cruzi, even though all the pathways in which this enzyme participates during the replication stress response remains elusive.

4.
Int J Radiat Oncol Biol Phys ; 109(2): 485-494, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33007435

RESUMO

PURPOSE: To compare global health-related quality of life (HRQoL) and overall survival (OS) in patients with head and neck cancer treated with intensity modulated radiation therapy (IMRT), conformal radiation therapy (3DCRT) or conventional radiation therapy (2DRT). METHODS AND MATERIALS: In this real-world, multi-institutional and prospective study, HRQoL outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Head and Neck 43 (H&N43) questionnaires. Item response theory was used to generate a global HRQoL score, based on the 71 questions from both forms. The effect of treatment modality on HRQoL was studied using multivariate regression analyses. Survival was estimated using the Kaplan-Meyer method, and groups were compared by the log-rank test. RESULTS: Five hundred and seventy patients from 13 institutions were included. Median follow-up was 12.2 months. Concerning the radiation technique, 29.5% of the patients were treated with 2DRT, 43.7% received 3DCRT, and 26.8% were treated with IMRT. A higher proportion of patients receiving 2DRT had a treatment interruption of more than 5 days (69% vs 50.2% for 3DCRT and 42.5% for IMRT). IMRT had a statistically significant positive effect on HRQoL compared with 3DCRT (ß= 2.627, standard error = 0.804, P = .001) and 2DRT had a statistically significant negative effect compared with 3DCRT (ß= -5.075, standard error = 0.926, P < .001). Patients receiving 2DRT presented a worse OS (P = .01). There were no differences in OS when IMRT was compared with 3DCRT. CONCLUSIONS: IMRT provided better HRQoL than 3DCRT, which provided better HRQoL than 2DRT. Patients receiving 2DRT presented a worse OS, which might be related to more frequent treatment interruptions.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Qualidade de Vida , Radioterapia de Intensidade Modulada , Idoso , Brasil , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
5.
Front Cell Dev Biol, v. 9, 633195w, maio. 2021
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-3817

RESUMO

DNA topoisomerases are enzymes that modulate DNA topology. Among them, topoisomerase 3α is engaged in genomic maintenance acting in DNA replication termination, sister chromatid separation, and dissolution of recombination intermediates. To evaluate the role of this enzyme in Trypanosoma cruzi, the etiologic agent of Chagas disease, a topoisomerase 3α knockout parasite (TcTopo3α KO) was generated, and the parasite growth, as well as its response to several DNA damage agents, were evaluated. There was no growth alteration caused by the TcTopo3α knockout in epimastigote forms, but a higher dormancy rate was observed. TcTopo3α KO trypomastigote forms displayed reduced invasion rates in LLC-MK2 cells when compared with the wild-type lineage. Amastigote proliferation was also compromised in the TcTopo3α KO, and a higher number of dormant cells was observed. Additionally, TcTopo3α KO epimastigotes were not able to recover cell growth after gamma radiation exposure, suggesting the involvement of topoisomerase 3α in homologous recombination. These parasites were also sensitive to drugs that generate replication stress, such as cisplatin (Cis), hydroxyurea (HU), and methyl methanesulfonate (MMS). In response to HU and Cis treatments, TcTopo3α KO parasites showed a slower cell growth and was not able to efficiently repair the DNA damage induced by these genotoxic agents. The cell growth phenotype observed after MMS treatment was similar to that observed after gamma radiation, although there were fewer dormant cells after MMS exposure. TcTopo3α KO parasites showed a population with sub-G1 DNA content and strong γH2A signal 48 h after MMS treatment. So, it is possible that DNA-damaged cell proliferation due to the absence of TcTopo3α leads to cell death. Whole genome sequencing of MMS-treated parasites showed a significant reduction in the content of the multigene families DFG-1 and RHS, and also a possible erosion of the sub-telomeric region from chromosome 22, relative to non-treated knockout parasites. Southern blot experiments suggest telomere shortening, which could indicate genomic instability in TcTopo3α KO cells owing to MMS treatment. Thus, topoisomerase 3α is important for homologous recombination repair and replication stress in T. cruzi, even though all the pathways in which this enzyme participates during the replication stress response remains elusive.

6.
Chaos ; 30(7): 073141, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32752616

RESUMO

In this paper, we investigated the possibility of using the magnetic Laplacian to characterize directed networks. We address the problem of characterization of network models and perform the inference of the parameters used to generate these networks under analysis. Many interesting results are obtained, including the finding that the community structure is related to rotational symmetry in the spectral measurements for a type of stochastic block model. Due the hermiticity property of the magnetic Laplacian we show here how to scale our approach to larger networks containing hundreds of thousands of nodes using the Kernel Polynomial Method (KPM), a method commonly used in condensed matter physics. Using a combination of KPM with the Wasserstein metric, we show how we can measure distances between networks, even when these networks are directed, large, and have different sizes, a hard problem that cannot be tackled by previous methods presented in the literature.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32117793

RESUMO

The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected tropical disease that affects around 8 million people worldwide. Chagas disease can be divided into two stages: an acute stage with high parasitemia followed by a low parasitemia chronic stage. Recently, the importance of dormancy concerning drug resistance in T. cruzi amastigotes has been shown. Here, we quantify the percentage of dormant parasites from different T. cruzi DTUs during their replicative epimastigote and amastigote stages. For this study, cells of T. cruzi CL Brener (DTU TcVI); Bug (DTU TcV); Y (DTU TcII); and Dm28c (DTU TcI) were used. In order to determine the proliferation rate and percentage of dormancy in epimastigotes, fluorescent-labeled cells were collected every 24 h for flow cytometer analysis, and cells showing maximum fluorescence after 144 h of growth were considered dormant. For the quantification of dormant amastigotes, fluorescent-labeled trypomastigotes were used for infection of LLC-MK2 cells. The number of amastigotes per infected LLC-MK2 cell was determined, and those parasites that presented fluorescent staining after 96 h of infection were considered dormant. A higher number of dormant cells was observed in hybrid strains when compared to non-hybrid strains for both epimastigote and amastigote forms. In order to investigate, the involvement of homologous recombination in the determination of dormancy in T. cruzi, we treated CL Brener cells with gamma radiation, which generates DNA lesions repaired by this process. Interestingly, the dormancy percentage was increased in gamma-irradiated cells. Since, we have previously shown that naturally-occurring hybrid T. cruzi strains present higher transcription of RAD51-a key gene in recombination process -we also measured the percentage of dormant cells from T. cruzi clone CL Brener harboring single knockout for RAD51. Our results showed a significative reduction of dormant cells in this T. cruzi CL Brener RAD51 mutant, evidencing a role of homologous recombination in the process of dormancy in this parasite. Altogether, our data suggest the existence of an adaptive difference between T. cruzi strains to generate dormant cells, and that homologous recombination may be important for dormancy in this parasite.


Assuntos
Recombinação Homóloga , Trypanosoma cruzi/genética , Trypanosoma cruzi/fisiologia , Animais , Linhagem Celular , Macaca mulatta , Mutação , Proteínas de Protozoários/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA de Protozoário/genética , Rad51 Recombinase/genética , Especificidade da Espécie , Trypanosoma cruzi/citologia , Trypanosoma cruzi/crescimento & desenvolvimento
8.
Phys Rev E ; 102(6-1): 062305, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33465954

RESUMO

Previous literature on random matrix and network science has traditionally employed measures derived from nearest-neighbor level spacing distributions to characterize the eigenvalue statistics of random matrices. This approach, however, depends crucially on eigenvalue unfolding procedures, which in many situations represent a major hindrance due to constraints in the calculation, especially in the case of complex spectra. Here we study the spectra of directed networks using the recently introduced ratios between nearest and next-to-nearest eigenvalue spacing, thus circumventing the shortcomings imposed by spectral unfolding. Specifically, we characterize the eigenvalue statistics of directed Erdos-Rényi (ER) random networks by means of two adjacency matrix representations, namely, (1) weighted non-Hermitian random matrices and (2) a transformation on non-Hermitian adjacency matrices which produces weighted Hermitian matrices. For both representations, we find that the distribution of spacing ratios becomes universal for a fixed average degree, in accordance with undirected random networks. Furthermore, by calculating the average spacing ratio as a function of the average degree, we show that the spectral statistics of directed ER random networks undergoes a transition from Poisson to Ginibre statistics for model 1 and from Poisson to Gaussian unitary ensemble statistics for model 2. Eigenvector delocalization effects of directed networks are also discussed.

9.
Phys Rev E ; 100(4-1): 042302, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31770973

RESUMO

Despite the great attention devoted to the study of phase oscillators on complex networks in the last two decades, it remains unclear whether scale-free networks exhibit a nonzero critical coupling strength for the onset of synchronization in the thermodynamic limit. Here, we systematically compare predictions from the heterogeneous degree mean-field (HMF) and the quenched mean-field (QMF) approaches to extensive numerical simulations on large networks. We provide compelling evidence that the critical coupling vanishes as the number of oscillators increases for scale-free networks characterized by a power-law degree distribution with an exponent 2<γ≤3, in line with what has been observed for other dynamical processes in such networks. For γ>3, we show that the critical coupling remains finite, in agreement with HMF calculations and highlight phenomenological differences between critical properties of phase oscillators and epidemic models on scale-free networks. Finally, we also discuss at length a key choice when studying synchronization phenomena in complex networks, namely, how to normalize the coupling between oscillators.

10.
PLoS Negl Trop Dis ; 12(11): e0006875, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30422982

RESUMO

In Trypanosoma cruzi, the etiologic agent of Chagas disease, Rad51 (TcRad51) is a central enzyme for homologous recombination. Here we describe the different roles of TcRad51 in DNA repair. Epimastigotes of T. cruzi overexpressing TcRAD51 presented abundant TcRad51-labeled foci before gamma irradiation treatment, and a faster growth recovery when compared to single-knockout epimastigotes for RAD51. Overexpression of RAD51 also promoted increased resistance against hydrogen peroxide treatment, while the single-knockout epimastigotes for RAD51 exhibited increased sensitivity to this oxidant agent, which indicates a role for this gene in the repair of DNA oxidative lesions. In contrast, TcRad51 was not involved in the repair of crosslink lesions promoted by UV light and cisplatin treatment. Also, RAD51 single-knockout epimastigotes showed a similar growth rate to that exhibited by wild-type ones after treatment with hydroxyurea, but an increased sensitivity to methyl methane sulfonate. Besides its role in epimastigotes, TcRad51 is also important during mammalian infection, as shown by increased detection of T. cruzi cells overexpressing RAD51, and decreased detection of single-knockout cells for RAD51, in both fibroblasts and macrophages infected with amastigotes. Besides that, RAD51-overexpressing parasites infecting mice also presented increased infectivity and higher resistance against benznidazole. We thus show that TcRad51 is involved in the repair of DNA double strands breaks and oxidative lesions in two different T. cruzi developmental stages, possibly playing an important role in the infectivity of this parasite.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Proteínas de Protozoários/metabolismo , Rad51 Recombinase/metabolismo , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética , Animais , Doença de Chagas/parasitologia , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA/efeitos da radiação , Humanos , Masculino , Camundongos , Estresse Oxidativo , Proteínas de Protozoários/genética , Rad51 Recombinase/genética , Trypanosoma cruzi/metabolismo , Trypanosoma cruzi/efeitos da radiação , Raios Ultravioleta
11.
Parasitology ; 144(11): 1498-1510, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28653592

RESUMO

Trypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. Remarkably, T. cruzi's antioxidant repertoire does not include catalase. In an attempt to shed light on what are the reasons by which this parasite lacks this enzyme, a T. cruzi cell line stably expressing catalase showed an increased resistance to hydrogen peroxide (H2O2) when compared with wild-type cells. Interestingly, preconditioning carried out with low concentrations of H2O2 led untransfected parasites to be as much resistant to this oxidant as cells expressing catalase, but did not induce the same level of increased resistance in the latter ones. Also, presence of catalase decreased trypanothione reductase and increased superoxide dismutase levels in T. cruzi, resulting in higher levels of residual H2O2 after challenge with this oxidant. Although expression of catalase contributed to elevated proliferation rates of T. cruzi in Rhodnius prolixus, it failed to induce a significant increase of parasite virulence in mice. Altogether, these results indicate that the absence of a gene encoding catalase in T. cruzi has played an important role in allowing this parasite to develop a shrill capacity to sense and overcome oxidative stress.


Assuntos
Catalase/metabolismo , Estresse Oxidativo , Transdução de Sinais , Trypanosoma cruzi/metabolismo , Animais , Catalase/genética , Linhagem Celular , Doença de Chagas/parasitologia , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Camundongos , NADH NADPH Oxirredutases/metabolismo , Rhodnius/parasitologia , Superóxido Dismutase/metabolismo , Transfecção , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/patogenicidade
12.
Infect Genet Evol ; 44: 318-329, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27456281

RESUMO

Corynebacterium pseudotuberculosis is the etiological agent of caseous lymphadenitis, a disease that predominantly affects small ruminants, causing significant economic losses worldwide. As a facultative intracellular pathogen, this bacterium is exposed to an environment rich in reactive oxygen species (ROS) within macrophages. To ensure its genetic stability, C. pseudotuberculosis relies on efficient DNA repair pathways for excision of oxidative damage such as 8-oxoguanine, a highly mutagenic lesion. MutY is an adenine glycosylase involved in adenine excision from 8-oxoG:A mismatches avoiding genome mutation incorporation. The purpose of this study was to characterize MutY protein from C. pseudotuberculosis and determine its involvement with DNA repair. In vivo functional complementation assay employing mutY gene deficient Escherichia coli transformed with CpmutY showed a 13.5-fold reduction in the rate of spontaneous mutation, compared to cells transformed with empty vector. Also, under oxidative stress conditions, CpMutY protein favored the growth of mutY deficient E. coli, relative to the same strain in the absence of CpMutY. To demonstrate the involvement of this enzyme in recognition and excision of 8-oxoguanine lesion, an in vitro assay was performed. CpMutY protein was capable of recognizing and excising 8-oxoG:A but not 8-oxoG:C presenting evidences of glycosylase/AP lyase activity in vitro. In silico structural characterization revealed the presence of preserved motifs related to the MutY activity on DNA repair, such as catalytic residues involved in glycosylase/AP lyase activity and structural DNA-binding elements, such as the HhH motif and the [4Fe-4S] cluster. The three-dimensional structure of CpMutY, generated by comparative modeling, exhibits a catalytic domain very similar to that of E. coli MutY. Taken together, these results indicate that the CpmutY encodes a functional protein homologous to MutY from E. coli and is involved in the prevention of mutations and the repair of oxidative DNA lesions.


Assuntos
Corynebacterium pseudotuberculosis/genética , Corynebacterium pseudotuberculosis/metabolismo , DNA Glicosilases/metabolismo , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Mutação , Fenótipo , Sequência de Aminoácidos , DNA Glicosilases/química , DNA Glicosilases/deficiência , DNA Glicosilases/genética , Reparo do DNA , Ativação Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Guanina/análogos & derivados , Guanina/metabolismo , Modelos Moleculares , N-Glicosil Hidrolases/metabolismo , Conformação de Ácido Nucleico , Estresse Oxidativo , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes
13.
PLoS One ; 11(7): e0156544, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27367229

RESUMO

INTRODUCTION: To report a single-institutional experience with the use of Superficial X-Ray Therapy (SXRT) for head and neck non-melanoma skin cancer (N-MSC) and to compare outcomes by prescribed fractionation schedules. MATERIALS AND METHODS: The medical records of 597 patients with 1021 lesions (720 BCC, 242 SCC, 59 SCC in situ) treated with kilovoltage radiation from 1979-2013 were retrospectively reviewed. The majority of patients were treated according to 1 of 3 institutional protocols based on the discretion of the radiation oncologist: 1) 22 x 2.5 Gy; 2) 20 x 2.5 Gy; 3) 30 x 2.0 Gy. "T" stage at first presentation was as follows: Tis (59); T1 (765); T2 (175); T3 (6), T4 (9); Tx, (7). All patients were clinical N0 and M0 at presentation. Chi-square test was used to evaluate any potential association between variables. The Kaplan-Meier method was used to analyze survival with the Log Rank test used for comparison. A Cox Regression analysis was performed for multivariate analysis. RESULTS: The median follow up was 44 months. No significant difference was observed among the 3 prescribed fractionation schemes (p = 0.78) in terms of RTOG toxicity. There were no failures among SCC in situ, 37 local failures (23 BCC, 14 SCC), 5 regional failures (all SCC) and 2 distant failures (both SCC). For BCC, the 5-year LC was 96% and the 10-year LC was 94%. For SCC the corresponding rates of local control were 92% and 87%, respectively (p = 0.03). The use of >2.0 Gy daily was significantly associated with improved LC on multivariate analysis (HR: 0.17; CI 95%: 0.05-0.59). CONCLUSION: SXRT for N-MSC of the head and neck is well tolerated, achieves excellent local control, and should continue to be recommended in the management of this disease. Fractionation schedules using >2.0 Gy daily appear to be associated with improved LC.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Cutâneas/radioterapia , Terapia por Raios X , Adulto , Idoso , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
14.
Gene ; 575(2 Pt 1): 233-43, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26341054

RESUMO

The GO-system is a DNA repair mechanism that prevents and corrects oxidative DNA damage. Formamidopyrimidine-DNA glycosylase (FPG/MutM) participates in this system, avoiding the mutagenic effects of 8-oxoguanine lesion into DNA. Corynebacterium pseudotuberculosis, the etiological agent of caseous lymphadenitis, is a facultative intracellular microorganism vulnerable to oxidative DNA damage. Since inefficiencies in the DNA damage repair system can lead to death, the characterization of repair genes may provide valuable molecular targets for caseous lymphadenitis therapy. The purposes of this study were to functionally characterize MutM1 and MutM2 proteins from C. pseudotuberculosis in silico, in vivo, and in vitro and to examine their role in the repair of 8-oxoguanine damage. In silico investigation revealed that both proteins have conserved domains typical of DNA glycosylases, such as DNA binding domains and DNA glycosylase/AP lyase catalytic domain. In comparison with the MutM protein of Escherichia coli, however, CpMutM2 was found to lack residues that are essential for recognizing and excising 8-oxoguanine damage. Molecular docking calculations have shown a native-like orientation of 8-oxoguanine at the CpMutM1 active site, while the same is not observed for CpMutM2, which seems to poorly interact with DNA. Surface charge analyses have corroborated this finding. Overexpression of CpMutM1 or CpMutM2 has toxic effects on E. coli strain BH20 (mutM-), as shown by growth curves obtained in the presence of hydrogen peroxide and cell viability assays. This cytotoxicity can be attributed to an imbalance in the repair pathway, resulting from hyperactivity of DNA glycosylases, leading to formation of AP sites and DNA strand breakage at levels that exceed the processing capacity of other enzymes in the BER pathway. In order to demonstrate the involvement of these enzymes in the recognition and excision of 8-oxoguanine lesion, glycosylase activity was evaluated in vitro. Only the CpMutM1 protein was proven to be capable of recognizing and excising 8-oxoguanine. Taken together, these results suggest that although the formamidopyrimidine-DNA glycosylase domain is conserved in both proteins, only one proved to be functional in recognizing and excising 8-oxoguanine lesion.


Assuntos
Proteínas de Bactérias , Corynebacterium pseudotuberculosis , DNA Bacteriano/metabolismo , DNA-Formamidopirimidina Glicosilase , Genoma Bacteriano , Guanina/análogos & derivados , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Corynebacterium pseudotuberculosis/enzimologia , Corynebacterium pseudotuberculosis/genética , DNA Bacteriano/genética , DNA-Formamidopirimidina Glicosilase/genética , DNA-Formamidopirimidina Glicosilase/metabolismo , Guanina/metabolismo
15.
Rev. méd. Minas Gerais ; 20(2,supl.1): S68-S72, abr.-jun. 2010.
Artigo em Português | LILACS | ID: lil-600021

RESUMO

A síndrome de transfusão feto-fetal (STFF) é uma das complicações mais graves que pode ocorrer em gestações gemelares monocoriônicas. Sua incidência varia de 1:40 a 1:60 em gestações gemelares e de 10 a 20 das gemelares monocoriônicas. Sua fisiopatologia é explicada pelo desequilíbrio das anastomoses vasculares placentárias e a resposta cardiovascular a essa alteração. A taxa de mortalidade sem tratamento é de 70 a 100 para pelo menos um dos gêmeos e não existe consenso bem definido sobre qual o melhor momento para se realizar o tratamento nem sobre a técnica a ser utilizada.


Twin-twin transfusion syndrome (TTTS) is one of the most serious complications that can occur in monochorionic twin pregnancies. The incidence of TTTS ranges from 1:40 to 1:60 in twin pregnancies and 10-20 in monochorionic twin pregnancies. The pathophysiology of the disease is explained by the imbalance of placental vascular anastomoses and the cardiovascular response to this alteration. The mortality rate without treatment is 70-100 for at least one of the twins and there is no clear consensus about the best time to perform the treatment or wich technique shoud be used.


Assuntos
Humanos , Feminino , Gravidez , Complicações na Gravidez , Transfusão Feto-Fetal/fisiopatologia , Transfusão Feto-Fetal/terapia , Transfusão Feto-Fetal/classificação , Transfusão Feto-Fetal/diagnóstico
16.
Rev. méd. Minas Gerais ; 20(2,supl.1): S107-S109, abr.-jun. 2010.
Artigo em Português | LILACS | ID: lil-600031

RESUMO

O descolamento prematuro da placenta (DPP) caracteriza-se pelo despregamento espontâneo da placenta a partir da vigésima semana de gravidez ou durante o parto. Este artigo relata o DPP oculto que culminou em óbito do concepto, apesar da abordagem adequada e imediata. Alerta para a possibilidade de diagnóstico de DPP em urgência obstétrica, com repercussões graves e potencialmente fatais para a mãe e o concepto se não identificado e abordado convenientemente.


Placental abruption (PA) is characterized by spontaneous detachment of the placenta from the twentieth week of gestation or during delivery. Here we report a case of concealed PA that culminated in death of the fetus in spite of appropriate and immediate approach of physicians. The case alerts us to the possibility of diagnosis of PA in na obstetric emergency. If not identified and addressed appropriately, PA could cause serious and potentially fatal implications for the mother and fetus.


Assuntos
Humanos , Masculino , Feminino , Gravidez , Recém-Nascido , Adulto , Descolamento Prematuro da Placenta/diagnóstico , Natimorto , Complicações na Gravidez , Hemorragia Uterina
17.
Rev. bras. cardiol. (Impr.) ; 23(2): 143-145, mar.-abr. 2010. ilus
Artigo em Português | LILACS | ID: lil-564574

RESUMO

Relata-se caso de esclerose tuberosa (ET) diagnosticada a partir de arritmia cardíaca fetal e múltiplos rabdomiomas cardíacos. A ET é doença autossômica dominante, multissistêmica, com incidência de 1:10000 nascimentos, caracterizada por múltiplos hamartomas em órgãos de origem mesodérmica e ectodérmica. O rabdomioma é o tumor primário do coração mais frequênte na infância, associando-se à ET em 50 por cento dos casos. Outras manifestações incluem epilepsia, retardo mental e alterações compressivas nos órgãos acometidos. A ET tem graves manifestações físicas e psicológicas, exigindo acompanhamento multidisciplinar. Objetiva-se propiciar o entendimento e o reconhecimento da doença, integrando os profissionais envolvidos no seu manejo.


Assuntos
Humanos , Feminino , Lactente , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico , Rabdomioma/complicações , Rabdomioma/diagnóstico
18.
Recurso educacional aberto em Português | CVSP - Brasil | ID: una-8136

RESUMO

Médicos discutem nesse vídeo sobre o contexto da dengue, uma das arboviroses mais importantes, que apresenta milhões de casos anualmente, sendo uma doença dinâmica e sistêmica. Seu manejo oportuno pode fazer a diferença. O tratamento indicado em todos os casos é a hidratação. Os médicos apontam aspectos de conduta e características do manejo da dengue, bem como a classificação do paciente no fluxograma da dengue. A organização da assistência deve ser articulada, integrando todos os profissionais com continuidade, visando o melhor desfecho, bem como remetem a outras arboviroses mais frequentes.


Assuntos
Dengue , Diagnóstico Diferencial , Infecções por Arbovirus
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