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1.
J Appl Microbiol ; 130(6): 1925-1934, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33128257

RESUMO

AIM: The purpose of this study was to evaluate the antifungal activity and toxicological parameters of 8-hydroxyquinoline derivatives PH151 and PH153 using alternative animal models, to understand their behaviour when subjected to in vivo experiments. METHODS AND RESULTS: We used Toll-deficient Drosophila melanogaster to test the protective effect of compounds against Candida albicans infection. Toxicological parameters were investigated in chicken and zebrafish embryos. PH151 and PH153 showed low toxicity and the treated flies with these compounds had a significantly higher survival rate than untreated flies after 7 days of infection. The compounds did not cause interruption of chicken embryogenesis. Zebrafish embryos exposed to compounds showed dose-dependent toxicity. CONCLUSIONS: The data supported the potential of PH151 and PH153 for the treatment of systemic candidiasis and demonstrated to be appropriate drug candidates for further studies using mammalian models. SIGNIFICANCE AND IMPACT OF THE STUDY: The increased incidence of Candida infections resistant to antifungals currently available requires acceleration of the discovery of new agents with properties of inhibiting this fungal pathogen. In this study, we have described the antifungal potential and toxicity of two 8-hydroxyquinoline derivatives using in vivo alternative models, and the results confirm their potential to be developed as new drug candidates.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Oxiquinolina/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candidíase/microbiologia , Embrião de Galinha , Drosophila melanogaster , Oxiquinolina/química , Sulfonamidas/química , Peixe-Zebra
2.
J Chem Phys ; 150(19): 194307, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31117791

RESUMO

We report experimental measurements of the absolute total cross sections (TCSs) for electron scattering from 1-butanol at impact energies in the range 80-400 eV. Those measurements were conducted by considering the attenuation of a collimated electron beam, at a given energy, through a gas cell containing 1-butanol, at a given pressure, and through application of the Beer-Lambert law to derive the required TCS. We also report theoretical results using the Independent-Atom Model with Screening Corrected Additivity Rule and Interference approach. Those results include the TCS, the elastic integral cross section (ICS), the ionization total ICS, and the sum over all excitation process ICSs with agreement at the TCS level between our measured and calculated results being encouraging.

3.
J Chem Phys ; 147(19): 194307, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29166110

RESUMO

Absolute total cross section (TCS) measurements for electron scattering from 1-propanol molecules are reported for impact energies from 40 to 500 eV. These measurements were obtained using a new apparatus developed at Juiz de Fora Federal University-Brazil, which is based on the measurement of the attenuation of a collimated electron beam through a gas cell containing the molecules to be studied at a given pressure. Besides these experimental measurements, we have also calculated TCS using the Independent-Atom Model with Screening Corrected Additivity Rule and Interference (IAM-SCAR+I) approach with the level of agreement between them being typically found to be very good.

4.
J Neurol Neurosurg Psychiatry ; 87(7): 754-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27071647

RESUMO

BACKGROUND: Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. METHODS: MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. RESULTS: Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. CONCLUSIONS: In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies.


Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Doenças Desmielinizantes/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Tamanho do Órgão/fisiologia , Adulto , Algoritmos , Atrofia , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
5.
Neurochem Res ; 41(1-2): 116-29, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26518676

RESUMO

We aimed to investigate the potential beneficial effects of the Brazilian Pampa biome honey in a Drosophila-based hypoxia model. Adult flies were reared in standard medium in the presence or absence of honey (at a final concentration of 10 % in medium). Then, control flies (4 % sucrose in medium) and honey-treated flies were submitted to hypoxia. Subsequently, flies were analyzed for mortality, neurolocomotor behavior (negative geotaxis), mitochondrial/oxidative stress parameters and expression of hypoxia/stress related genes by RT-qPCR. The HPLC analysis revealed the presence of phenolics and flavonoids in the studied honey. Caffeic acid was the major compound followed by p-coumaric acid and kaempferol. The presence of such compounds was correlated with a substantial antioxidant activity in vitro. Flies subjected to hypoxia presented marked mortality, locomotor deficits and changes in oxidative stress and mitochondrial activity parameters. Honey treatment was able to completely block mortality and locomotor phenotypes. In addition, honey was able to reverse ROS production and hypoxia-induced changes in mitochondrial complex I and II activity. Hypoxia also induced an up-regulation in mRNA expression of Sima (HIF-1), NFκß, NRF2, HOX, AKT-1, InR, dILP2, dILP5 and HSP27. Honey treatment was not able to modulate changes in the tested genes, indicating that its protective effects involve additional mechanisms other than transcriptional activity of hypoxia-driven adaptive responses in flies. Our results demonstrated, for the first time, the beneficial effects of honey against the deleterious effects of hypoxia/reperfusion processes in a complex organism.


Assuntos
Mel , Locomoção , Estresse Oxidativo , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/farmacologia , Cromatografia Líquida de Alta Pressão , Drosophila melanogaster/genética , Flavonoides/análise , Expressão Gênica , Mel/análise , Fenóis/análise , Espectrofotometria Ultravioleta
6.
Genet Mol Res ; 15(2)2016 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-27421014

RESUMO

Hemoglobin (Hb) variants involving alpha-chains are less common in the global population than Hb variants resulting from beta-chain alterations. Generally, alpha-chain Hb variants are caused by point mutations affecting alpha-1 and/or alpha-2 genes of the alpha-globin cluster (HBA1 and HBA2). In Brazil, the most prevalent alpha-chain Hb variant is Hb Hasharon. In this study, we present the first case of an Hb Val de Marne variant in the Americas, specifically in Brazil.


Assuntos
Hemoglobinas Anormais/genética , Adulto , Substituição de Aminoácidos , Brasil , Feminino , Genética Populacional , Genótipo , Hemoglobinas Anormais/metabolismo , Humanos , Mutação , Mutação Puntual
7.
J Pediatr Gastroenterol Nutr ; 58(4): 486-90, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24253365

RESUMO

OBJECTIVE: Child abuse leads to multiple physical and psychosomatic sequelae. The aim of the present study was to evaluate the association between child abuse and constipation among schoolchildren. METHODS: Children 13 to 18 years of age were selected from 4 semiurban schools in Gampaha District, Sri Lanka. A self-administered questionnaire was used for data collection. Information regarding sociodemographic factors and gastrointestinal symptoms, child abuse, and somatisation were collected. Constipation was diagnosed using Rome III criteria. RESULTS: A total of 1792 children were included in the analysis (boys 975 [54.4%], mean age 14.4 years, standard deviation [SD] 1.3 years). One hundred thirty-eight (7.7%) fulfilled Rome III criteria for constipation. The number of children exposed to physical, emotional, and sexual abuse were, respectively, 438 (24.4%), 396 (22.1%), and 51 (2.8%). The prevalence of constipation was significantly higher in those exposed to sexual (5.8% vs 2.6% P = 0.03), emotional (40.9% vs 20.8%, P < 0.0001), and physical abuse (41.6% vs 23.2%, P < 0.0001). Mean somatisation score was higher in the total group of abused children with constipation (mean 18.6, SD 12.5) compared with those without (mean 13.9, SD 12.3; P = 0.027). Children with a history of abuse did not seek health care more often than children without this history. Patient-perceived severity of bowel symptoms was higher in children with physical abuse (23.7 vs 19.7 P = 0.001) and emotional abuse (25.4 vs 19.3 P < 0.0001). CONCLUSIONS: Childhood constipation shows a significant association with physical, sexual, and emotional abuse. Children with constipation complain of more somatic symptoms and bowel symptoms when they are exposed to abuse.


Assuntos
Abuso Sexual na Infância/estatística & dados numéricos , Constipação Intestinal/epidemiologia , Transtornos Somatoformes/epidemiologia , Adolescente , Constipação Intestinal/diagnóstico , Constipação Intestinal/psicologia , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Percepção , Prevalência , Índice de Gravidade de Doença , Fatores Sexuais , Transtornos Somatoformes/psicologia , Sri Lanka/epidemiologia , Inquéritos e Questionários
8.
Genet Mol Res ; 12(4): 6762-6, 2013 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-24391023

RESUMO

Sickle cell anemia is an affection that causes chronic inflammation, with consequences for vaso-occlusion, oxidative stress and cytokine production. Genetic polymorphisms in markers involved in this process can modulate the inflammatory response, including polymorphisms -308G/A of TNFA (tumor necrosis factor alpha) and -509C/T of TGFB1 (transforming growth factor beta 1), reported to increase TNF-α and TGF-ß1 production, respectively. Changes in the cytokine balance are important risk factors for clinical events; consequently, we examined the frequencies of these polymorphisms in 240 Brazilian sickle cell anemia patients from southeast Brazil. PCR-RFLP was used to detect these polymorphisms. The -509C/T (TGFB1) polymorphism was more frequent than -308G/A (TNFA), with allelic frequency of 0.3 for the mutant allele T (TGFB) agaist 0.1 for the mutant allele A (TNFA). These allelic frequencies are similar to those known from populations with ethnicity similar to the Brazilian population. Inheritance of these polymorphisms does not seem to be associated with that of the Hb S mutation; however, this information could be useful in analyses of specific clinical characteristics of sickle cell anemia.


Assuntos
Anemia Falciforme/genética , Fator de Crescimento Transformador beta1/genética , Fator de Necrose Tumoral alfa/genética , Brasil , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Hemoglobina Falciforme/genética , Humanos , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta1/biossíntese , Fator de Necrose Tumoral alfa/biossíntese
9.
Front Endocrinol (Lausanne) ; 14: 1028285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814577

RESUMO

Background: There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. Objectives: To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). Methods: We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. Results: The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. Conclusions: The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.


Assuntos
Diabetes Mellitus Tipo 1 , Masculino , Feminino , Humanos , Criança , Sri Lanka , Irmãos , Glândula Tireoide , Prevalência , Autoanticorpos
11.
Braz J Biol ; 84: e249617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34730698

RESUMO

Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.


Assuntos
Hibernação , Lagartos , Animais , Eritrócitos , Oxirredução , Estresse Oxidativo
12.
Mol Microbiol ; 71(1): 185-97, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19007414

RESUMO

DNA polymerase kappa (Pol kappa) is a low-fidelity polymerase that has the ability to bypass several types of lesions. The biological role of this enzyme, a member of the DinB subfamily of Y-family DNA polymerases, has remained elusive. In this report, we studied one of the two copies of Pol kappa from the protozoan Trypanosoma cruzi (TcPol kappa). The role of this TcPol kappa copy was investigated by analysing its subcellular localization, its activities in vitro, and performing experiments with parasites that overexpress this polymerase. The TcPOLK sequence has the N-terminal extension which is present only in eukaryotic DinB members, but its C-terminal region is more similar to prokaryotic and archaeal counterparts since it lacks C(2)HC motifs and PCNA interaction domain. Our results indicate that in contrast to its previously described orthologues, this polymerase is localized to mitochondria. The overexpression of TcPOLK increases T. cruzi resistance to hydrogen peroxide, and in vitro polymerization assays revealed that TcPol kappa efficiently bypasses 8-oxoguanine lesions. Remarkably, our results also demonstrate that the DinB subfamily of polymerases can participate in homologous recombination, based on our findings that TcPol kappa increases T. cruzi resistance to high doses of gamma irradiation and zeocin and can catalyse DNA synthesis within recombination intermediates.


Assuntos
Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Guanina/análogos & derivados , Mitocôndrias/genética , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/genética , Sequência de Aminoácidos , Animais , Dano ao DNA , DNA de Protozoário/genética , DNA Polimerase Dirigida por DNA/genética , Guanina/metabolismo , Peróxido de Hidrogênio/farmacologia , Dados de Sequência Molecular , Estresse Oxidativo , Proteínas de Protozoários/genética , Recombinação Genética , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/metabolismo
13.
J Psychiatr Res ; 121: 91-100, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31785554

RESUMO

Permethrin (PM) is one of the most used synthetic pyrethroid worldwide. Exposure to this compound during pregnancy and early childhood has been indicated as a risk factor for neurodevelopmental disorders. We evaluated the long-term effects of embryonic PM exposure in different stages of zebrafish development. Briefly, embryos (3 hpf) were exposed to sub-lethal concentrations of PM (25 and 50 µg.L-1) during 24 h and then behavioral parameters were evaluated during embryonic (28 hpf), eleutheroembryonic (3 dpf), larval (7 dpf), and adult stages (90 dpf). PM exposure decreased spontaneous movement at 28 hpf and decreased thigmotaxis in eleutheroembryos. The long-term effects of PM include changes in non-motor behaviors such as fear and anxiety in larva and adults. Adults embryonically exposed to PM also showed a significant increase in aggressiveness parameters. These results demonstrated that embryonic exposure to PM induces persistent neurotoxic effects in adulthood, which can impair the cognitive and behavioral fitness of non-target species contributing to a rise in neurodevelopmental disorders.


Assuntos
Agressão/efeitos dos fármacos , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero , Inseticidas/efeitos adversos , Larva , Transtornos do Neurodesenvolvimento/etiologia , Permetrina/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Piretrinas/efeitos adversos , Peixe-Zebra , Animais , Modelos Animais de Doenças , Feminino , Masculino , Gravidez
14.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469248

RESUMO

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or tegu lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.


Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou teiú. Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.

15.
Braz. j. biol ; 84: e249617, 2024. graf
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1345540

RESUMO

Abstract Hibernation is a natural condition of animals that lives in the temperate zone, although some tropical lizards also experience hibernation annually, such as the lizard native from South America, Salvator merianae, or "tegu" lizard. Even though physiological and metabolic characteristic associated with hibernation have been extensively studied, possible alterations in the red blood cells (RBC) integrity during this period remains unclear. Dehydration and fasting are natural consequences of hibernating for several months and it could be related to some cellular modifications. In this study, we investigated if the osmotic tolerance of RBCs of tegu lizard under hibernation is different from the cells obtained from animals while normal activity. Additionally, we indirectly investigated if the RBCs membrane of hibernating tegus could be associated with oxidation by quantifying oxidized biomolecules and the activity of antioxidant enzymes. Our findings suggest that RBCs are more fragile during the hibernation period, although we did not find evidence of an oxidative stress scenario associated with the accentuated fragility. Even though we did not exclude the possibility of oxidative damage during hibernation, we suggested that an increased RBCs volume as a consequence of hypoosmotic blood during hibernation could also affect RBCs integrity as noted.


Resumo A hibernação é uma condição natural dos animais que vivem na zona temperada, embora alguns lagartos tropicais também experenciem hibernação anualmente, como é o caso do lagarto nativo da América do Sul, Salvator merianae ou "teiú". Embora as características fisiológicas e metabólicas associadas à hibernação tenham sido amplamente estudadas, possíveis alterações na integridade das hemácias durante esse período ainda permanecem obscuras. A desidratação e o jejum são consequências naturais da hibernação por vários meses e podem estar relacionadas a algumas modificações celulares. Neste estudo, investigamos se a tolerância osmótica de hemácias do lagarto teiú sob hibernação são diferentes das células obtidas de animais em atividade normal. Além disso, investigamos indiretamente por meio da quantificação de biomoléculas oxidadas e da atividade de enzimas antioxidantes se a membrana das hemácias dos teiús em hibernação poderia estar associada à oxidação. Nossos resultados sugerem que as hemácias possuem maior fragilidade durante o período de hibernação, embora não tenhamos encontrado evidências de um cenário de estresse oxidativo associado à essa fragilidade acentuada. Embora não tenhamos excluído a possibilidade de dano oxidativo durante a hibernação, sugerimos que um aumento no volume das hemácias como consequência de sangue hipoosmótico durante a hibernação também poderia afetar a integridade de hemácias, tal como foi observado.


Assuntos
Animais , Hibernação , Lagartos , Oxirredução , Estresse Oxidativo , Eritrócitos
16.
Braz J Med Biol Res ; 52(9): e8290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31482998

RESUMO

Tendon rupture is a very frequent accident involving average people and high-performance athletes. Clinical studies describe tendon recovery as a painful and slow process involving different biochemical and histological events. Ascorbic acid (AA) is a potent antioxidant as well as an important cofactor for collagen synthesis. In the current study, we evaluated if local treatment with AA is able to promote tendon repair in tenotomized rats. Animals were submitted to Achilles tendon rupture followed by surgical suture. Control and AA groups received in loco injection of saline solution (0.9% NaCl) and 30 mM AA, respectively. Histological and functional recovery of Achilles tendon tissue was evaluated at 7, 14, and 21 days post-surgery. Hematoxylin/eosin staining and collagen fluorescence analysis showed intense disarrangement of tendon tissue in the saline group. Tenotomized animals also showed hypercellularity in tendon tissue compared with non-tenotomized animals. The Achilles functional index (AFI) showed a significant decrease of tendon functionality in tenotomized animals at 7, 14, and 21 days post-surgery. AA accelerated tissue organization and the recovery of function of the Achilles tendons. The beneficial effect of AA treatment was also observed in the organization of the collagen network. Data presented in the current work showed that in loco treatment with AA accelerated the recovery of injured Achilles tendon post-surgery.


Assuntos
Tendão do Calcâneo/efeitos dos fármacos , Ácido Ascórbico/administração & dosagem , Colágeno/efeitos dos fármacos , Traumatismos dos Tendões/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Animais , Colágeno/fisiologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Tenotomia , Cicatrização/efeitos dos fármacos
17.
Artigo em Inglês | MEDLINE | ID: mdl-30543862

RESUMO

Given the increasing use of carbon nanotubes (CNT) in several industries and technological applications, it is essential to perform in vivo toxicological studies with these nanomaterials to evaluate their potential ecotoxicity. Dopamine (DA) and serotonin (5HT) are key neurotransmitters for brain functions and behavioral responses. Determination of DA and 5HT were performed in brain samples from zebrafish Danio rerio exposed i.p. to single-walled CNT (SWCNT), besides analyzing acetylcholinesterase (AChE) and ectonucleotidases activity, lipid peroxidation and total antioxidant capacity. Results showed that treatment with SWCNT increased between 3 and 6-fold the concentration of DA and 5HT (p < 0.05). Similarly, a significant reduction (p < 0.05) in AChE activity was observed in the brains of SWCNT exposed zebrafish when compared to the control groups. Cholinergic, serotonergic, and dopaminergic systems, through AChE activity and serotonin and dopamine levels, respectively were affected by SWCNT in the zebrafish brain. Alterations in these neurotransmitters can potentially affect several physiological and behavioral that they control.


Assuntos
Antioxidantes/metabolismo , Nanotubos de Carbono/toxicidade , Síndromes Neurotóxicas , Neurotransmissores/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peixe-Zebra
18.
DNA Repair (Amst) ; 73: 78-90, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30470509

RESUMO

Genomes are affected by a wide range of damage, which has resulted in the evolution of a number of widely conserved DNA repair pathways. Most of these repair reactions have been described in the African trypanosome Trypanosoma brucei, which is a genetically tractable eukaryotic microbe and important human and animal parasite, but little work has considered how the DNA damage response operates throughout the T. brucei life cycle. Using quantitative PCR we have assessed damage induction and repair in both the nuclear and mitochondrial genomes of the parasite. We show differing kinetics of repair for three forms of DNA damage, and dramatic differences in repair between replicative life cycle forms found in the testse fly midgut and the mammal. We find that mammal-infective T. brucei cells repair oxidative and crosslink-induced DNA damage more efficiently than tsetse-infective cells and, moreover, very distinct patterns of induction and repair of DNA alkylating damage in the two life cycle forms. We also reveal robust repair of DNA lesions in the highly unusual T. brucei mitochondrial genome (the kinetoplast). By examining mutants we show that nuclear alkylation damage is repaired by the concerted action of two repair pathways, and that Rad51 acts in kinetoplast repair. Finally, we correlate repair with cell cycle arrest and cell growth, revealing that induced DNA damage has strikingly differing effects on the two life cycle stages, with distinct timing of alkylation-induced cell cycle arrest and higher levels of damage induced death in mammal-infective cells. Our data reveal that T. brucei regulates the DNA damage response during its life cycle, a capacity that may be shared by many microbial pathogens that exist in variant environments during growth and transmission.


Assuntos
Dano ao DNA , Trypanosoma brucei brucei/crescimento & desenvolvimento , Trypanosoma brucei brucei/genética , Alquilação , Pontos de Checagem do Ciclo Celular/genética , Adutos de DNA/metabolismo , Reparo do DNA , DNA de Protozoário/genética , DNA de Protozoário/metabolismo , Estresse Oxidativo/genética , Rad51 Recombinase/metabolismo , Trypanosoma brucei brucei/citologia , Trypanosoma brucei brucei/metabolismo
19.
J Gastroenterol Hepatol ; 23(11): 1672-7, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18752559

RESUMO

BACKGROUND AND AIMS: Recurrent abdominal pain is common among children and adolescents. The majority of the affected patients have no apparent cause for their symptoms. This study evaluated gastric myoelectrical activity and motility abnormalities in children and adolescents with functional recurrent abdominal pain. METHODS: Forty-two children with functional recurrent abdominal pain [19 (45.2%) males, mean 8 years, SD 3 years, 19 functional abdominal pain, 9 irritable bowel syndrome, 9 functional dyspepsia, 1 abdominal migraine, 1 aerophagia and 3 non-specific abdominal pain according to Rome III criteria] and 20 healthy children [10 (50%) males, mean 9 years, SD 2.7 years] from the same geographical area underwent electrogastrography (EGG), and ultrasonographic assessment of gastric emptying rate and antral motility. RESULTS: Average gastric emptying rate, amplitude of antral contractions and antral motility index were lower in patients (46.5%, 74.3% and 6.5 respectively) compared to controls (66.17%, 89% and 8.3 respectively) (P < 0.001). Gastric emptying rate had a negative correlation with scores obtained for severity of symptoms (r = -0.63, P < 0.0001). Postprandial dominant frequency instability co-efficient (post-DFIC) was higher in patients than in controls (27.83% vs 18.3%, P = 0.0087), and correlated with the symptom score (r = 0.26, P = 0.045). CONCLUSIONS: Gastric emptying and antral motility were significantly impaired in patients, indicating a possible role for gastric motility disturbances in the pathogenesis of childhood functional recurrent abdominal pain. Further studies, including therapeutic trials, are needed to confirm this association and for recommendation of prokinetic drugs in its management.


Assuntos
Dor Abdominal/fisiopatologia , Esvaziamento Gástrico , Contração Muscular , Complexo Mioelétrico Migratório , Antro Pilórico/fisiopatologia , Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Adolescente , Estudos de Casos e Controles , Criança , Eletromiografia/métodos , Feminino , Humanos , Masculino , Medição da Dor , Período Pós-Prandial , Antro Pilórico/diagnóstico por imagem , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Sri Lanka , Estresse Psicológico/complicações , Ultrassonografia
20.
J Paediatr Child Health ; 44(4): 195-200, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18377368

RESUMO

AIMS: Recurrent abdominal pain (RAP) has a multifactorial aetiology with many affected children having no evidence of organic pathology. This study assessed the functional and organic causes for RAP in a cohort of Sri Lankan children. METHODS: Fifty-five Sri Lankan children (45.5% males, aged 5-15 years) having RAP were screened for organic diseases. RAP was defined using Apley criteria. Children without clinical or laboratory evidence of organic diseases were classified into functional gastrointestinal diseases (FGD) using Rome II and III criteria. Thirty-nine patients with functional RAP and 20 healthy children (50% males, age 5-15 years) from same area were tested for Helicobacter pylori using a stool antigen test. RESULTS: Thirteen (23.6%) children had organic RAP. According to Rome II, 33 (60%), and according to Rome III, 39 (71%) (functional abdominal pain 19, irritable bowel syndrome nine, functional dyspepsia nine, abdominal migraine one, aerophagia one) children had FGD. Two (5.1%) patients and one (5%) control tested were positive for Helicobacter pylori (P > 0.05). Except for constipation, pain characteristics and associated symptoms were not significantly different between organic and functional RAP. CONCLUSIONS: Organic pathology accounted for symptoms in less than a quarter of Sri Lankan children with RAP. The majority had functional bowel diseases, of which the commonest was functional abdominal pain. Rome III criteria were more effective than Rome II criteria in identifying FGD. Helicobacter pylori infection did not appear to be associated with RAP.


Assuntos
Dor Abdominal/etiologia , Gastroenteropatias/complicações , Adolescente , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Constipação Intestinal/complicações , Fezes/microbiologia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/microbiologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Sri Lanka
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