RESUMO
Mitochondrial DNA copy number (mtDNA-CN) measured from blood specimens is a minimally invasive marker of mitochondrial function that exhibits both inter-individual and intercellular variation. To identify genes involved in regulating mitochondrial function, we performed a genome-wide association study (GWAS) in 465,809 White individuals from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank (UKB). We identified 133 SNPs with statistically significant, independent effects associated with mtDNA-CN across 100 loci. A combination of fine-mapping, variant annotation, and co-localization analyses was used to prioritize genes within each of the 133 independent sites. Putative causal genes were enriched for known mitochondrial DNA depletion syndromes (p = 3.09 × 10-15) and the gene ontology (GO) terms for mtDNA metabolism (p = 1.43 × 10-8) and mtDNA replication (p = 1.2 × 10-7). A clustering approach leveraged pleiotropy between mtDNA-CN associated SNPs and 41 mtDNA-CN associated phenotypes to identify functional domains, revealing three distinct groups, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism. Finally, using mitochondrial SNPs, we establish causal relationships between mitochondrial function and a variety of blood cell-related traits, kidney function, liver function and overall (p = 0.044) and non-cancer mortality (p = 6.56 × 10-4).
Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial , Megacariócitos/fisiologia , Mitocôndrias/genética , Ativação Plaquetária , Polimorfismo de Nucleotídeo Único , Idoso , Proliferação de Células , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Nucleotídeos/metabolismo , FenótipoAssuntos
Parede Abdominal , Hérnia Abdominal , Hérnia Ventral , Hérnia Incisional , Parede Abdominal/cirurgia , Hérnia Abdominal/etiologia , Hérnia Abdominal/cirurgia , Hérnia Ventral/etiologia , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Humanos , Hérnia Incisional/etiologia , Hérnia Incisional/cirurgia , Telas Cirúrgicas/efeitos adversosRESUMO
BACKGROUND: Menopausal transition is a physiological process encompassing hormonal and body changes that impact women's health and life quality. This period may be characterized by the Stages of Reproductive Aging Workshop (STRAW + 10) criteria using menstrual patterns. Use of the STRAW + 10 is uncertain in HIV infection. We aimed to characterize menopausal transition in women with HIV (WWH) using the STRAW + 10 criteria, hormonal measures and menopause symptoms. METHODS: We performed a cross-sectional study, nested to the HIV-Infected Women's Cohort, in Rio de Janeiro, Brazil. Eligible women included those aged 30 years or older, without clinical or surgical menopause, hormonal contraception, replacement therapy and ovarian disorders. We conducted face-to-face interviews and collected blood samples for follicle stimulating hormone (FSH) and estradiol measures. RESULTS: We enrolled 328 WWH (28.3% of women in the cohort). The distribution of age, hormonal levels and reported symptoms per each STRAW + 10 stage was consistent with the expected distribution in the menopausal transition. Age and FSH significantly increased and estradiol decreased from stage -2 (7 + days of menstrual delay) to stage +2 (8 + years of amenorrhea). CONCLUSIONS: The present results support use of the STRAW + 10 to characterize the menopausal transition of WWH with good clinical and immunological control.
Assuntos
Envelhecimento/fisiologia , Infecções por HIV/fisiopatologia , HIV , Menopausa/fisiologia , Adulto , Brasil , Estudos de Coortes , Estudos Transversais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Pessoa de Meia-IdadeRESUMO
O objetivo foi avaliar protocolos de maturação in vitro (MIV) para oócitos de cutias, seguida de fertilização in vitro (FIV) e ativação partenogenética (AP). Os oócitos imaturos (CCOs) foram obtidos por fatiamento do ovário, após OSH, e submetidos a três grupos: MAT - 16 (16 horas de maturação), MAT - 20 (20 horas de maturação) e MAT - 24 (24 horas de maturação), em incubadora de cultivo a 38,8°C, com atmosfera de 5% de CO2 e 95% de umidade relativa. A maturação foi analisada pela presença do primeiro corpúsculo polar. Em seguida, os CCOs maduros foram submetidos à FIV, com período de coincubação dos CCOs e dos espermatozoides de 15h, a 38,8ºC e 5% de CO2, e AP com ionomicina. Os grupos de MIV foram analisados utilizando-se o teste qui-quadrado e, nos experimentos de FIV e AP, foram analisadas a taxa de clivagem e a proporção de desenvolvimento embrionário. A análise estatística foi realizada utilizando-se o programa SAS. Houve diferença significativa entre os grupos de maturação, tendo os grupos MAT - 20 e MAT - 24 apresentado maior porcentagem de oócitos maturados in vitro. As taxas de clivagem e de desenvolvimento embrionário foram de 8,6% e 2,9%, respectivamente, na FIV, e de 63,6% e 15,1%, na AP. Entretanto, nos dois casos, o embrião não passou do estágio de mórula.(AU)
The objective was to evaluate IVM protocols for agouti oocytes, followed by in vitro fertilization (IVF) and parthenogenetic activation (PA). The immature oocytes (CCOs) were obtained by slicing the ovary after OSH and submitted to three groups: MAT - 16 (16 hours maturation), MAT - 20 (20 hours maturation) and MAT - (24 hours maturation), in a culture incubator at 38.8°C, with an atmosphere of 5% CO2 and 95% relative humidity. The maturation was analyzed by the presence of the first polar corpuscle. Then, mature CCOs were submitted to IVF, with co-incubation period of CCOs and spermatozoa from 15h to 38.8°C and 5% of CO2, and PA with inomycin. The IVM groups were analyzed using the chi-square test and in the FIV and PA experiment the rate of cleavage and the rate of embryonic development were analyzed. Statistical analysis was performed using the SAS program. There was a significant difference between the maturation groups, and the MAT - 20 and MAT - 24 groups showed a higher percentage of matured oocytes in vitro. The rates of cleavage and embryonic development were 8.6% and 2.9%, respectively in FIV and 63.6% and 15.1% in PA. However, in both cases the embryo did not pass beyond the morula stage.(AU)
Assuntos
Animais , Oócitos , Fertilização in vitro/veterinária , Técnicas de Maturação in Vitro de Oócitos/veterinária , Dasyproctidae , Partenogênese , IonomicinaRESUMO
Este artigo apresenta um estudo metodológico de um procedimento experimental com duas tarefas de processamento categórico auditivo para fala. Na tarefa de identificação, o participante ouve sons que variam em duração de VOT e é solicitado a identificar a que palavra correspondem. Na tarefa de discriminação, o participante deve indicar se dois estímulos de VOT adjacentes são iguais ou diferentes. As estratégias de análises de dados para caracterizar o grau de categorização são apresentadas e são discutidas possibilidades de uso do procedimento em estudos.
This article presents a methodological study of an experimental procedure with two tasks of categorical auditory processing for speech. In the identification task, the participant hears sounds that vary in VOT duration and is asked to identify which word they correspond to. In the discrimination task, the participant must indicate whether two adjacent VOT stimuli are the same or different. The data analysis strategies to characterize the degree of categorization are presented and possibilities of using the procedure in studies are discussed.
Este artículo presenta un estudio metodológico de un procedimiento experimental con dos tareas de procesamiento auditivo categórico para el habla. En la tarea de identificación, el participante escucha sonidos que varían en la duración del VOT y se le pide que identifique a qué palabra corresponden. En la tarea de discriminación, el participante debe indicar si dos estímulos VOT adyacentes son iguales o diferentes. Se presentan las estrategias de análisis de datos para caracterizar el grado de categorización y se discuten las posibilidades de utilizar el procedimiento en los estudios.
RESUMO
There is a growing interest in the study of unspecialized mesenchymal stem cells, for there are still some discussions about their in vitro behavior. Regenerative medicine is a science undergoing improvement which develops treatments as cell therapy using somatic stem cells. In several studies, adipose tissue is presented as a source of multipotent adult cells that has several advantages over other tissue sources. This study aimed to characterize and evaluate the tagging of mesenchymal stem cells from the agoutis adipose tissue (Dasyprocta prymonolopha), with fluorescent intracytoplasmic nanocrystals. Fibroblast cells were observed, plastic adherent, with extended self-renewal, ability to form colonies, multipotency by differentiation into three lineages, population CD90 + and CD45 - expression, which issued high red fluorescence after the tagging with fluorescent nanocrystals by different paths and cryopreserved for future use. It is possible to conclude that mesenchymal stem cells from agouti adipose tissue have biological characteristics and in vitro behavior that demonstrate its potential for use in clinical tests.(AU)
Há um interesse crescente no estudo das células estaminais mesenquimais, não especializadas, pois ainda existem algumas discussões sobre seu comportamento in vitro. A medicina regenerativa é uma ciência em fase de crescimento que desenvolve tratamentos como terapia celular utilizando células estaminais somáticas. Em vários estudos, o tecido adiposo é apresentado como uma fonte de células adultas multipotentes que tem várias vantagens em relação a outras fontes de tecido. Este estudo teve como objetivo caracterizar e avaliar a marcação de células estaminais mesenquimais do tecido adiposo de cutias (Dasyprocta prymnolopha) com nanocristais intracitoplasmáticos fluorescentes. Observaram-se células fibroblásticas, aderentes ao plástico, com autorrenovação prolongada, capacidade de formar colônias, diferenciação em três linhagens, população CD90 + e expressão CD45, que emitiram alta fluorescência vermelha após a marcação com nanocristais fluorescentes por diferentes vias, e criopreservadas para uso futuro. É possível concluir que as células estaminais mesenquimais do tecido adiposo de cutias têm características biológicas e comportamentos in vitro que demonstram seu potencial para uso em testes clínicos.(AU)
Assuntos
Animais , Tecido Adiposo/citologia , Imunofenotipagem/veterinária , Medicina Regenerativa/métodos , Nanopartículas , Células-Tronco Mesenquimais , Dasyproctidae/genéticaRESUMO
Objetivou-se avaliar o comportamento ingestivo de cordeiros Santa Inês alimentados com resíduo de cervejaria desidratado (RCD). Foram utilizados 35 cordeiros, machos, não castrados, com peso médio inicial de 16,00±1,69kg e, aproximadamente, 70 dias de idade. Adotou-se o delineamento inteiramente ao acaso, com cinco tratamentos e sete repetições, consistindo os tratamentos em: 0; 20; 40; 60 e 80% de inclusão de RCD na porção concentrada da ração. A inclusão de RCD na ração não influenciou o tempo de alimentação (TAL; h/dia) e a eficiência de alimentação (gFDN/h; P>0,05). O TAL obtido neste estudo apresentou valor médio de 4,90h/dia. Observou-se efeito linear decrescente (P<0,05) com a inclusão do RCD, para as eficiências de alimentação (gMS/h) e ruminação (gMS/h e gFDN/h). Contudo, efeito linear crescente (P<0,05) foi constatado para tempo de ruminação e mastigação total, bem como para o número de mastigações merícicas por dia para os animais alimentados com o subproduto. A inclusão de resíduo de cervejaria desidratado influencia o comportamento ingestivo de cordeiros Santa Inês, diminuindo a eficiência de alimentação, quando relacionada ao consumo de matéria seca por hora, e aumentando o tempo de ruminação, podendo ser adicionado em até 20% na porção concentrada da ração.(AU)
The aim of this study was to evaluate the ingestive behavior of Santa Ines lambs fed dehydrated brewer's residue (DBR). Thirty-five male lambs were used, with an initial mean weight of 16.00±1.69kg and, approximately, 70 days of age. A completely randomized design was used, with five treatments and seven replicates, the treatments being: 0; 20; 40; 60 and 80% of inclusion of DBR in the concentrated portion of the ration. The inclusion of DBR in the ration did not influence feeding time (FT; h/day) and feeding efficiency (gNDF/h; P> 0.05). The FT obtained in this study had an average value of 4.90h/day. There was a decreasing linear effect (P< 0.05) for feed efficiency (gDM/h) and rumination efficiency (gDM/h and gNDF/h). However, linear increasing effect (P< 0.05) was observed for rumination and total chewing time, as well as for the number of chews per day for animals fed with the byproduct. The inclusion of dehydrated brewer's residue in the concentrate can influence the ingestive behavior of Santa Ines lambs, reducing feed efficiency, when related to the dry matter intake per hour, and increasing the total rumination time in Santa Ines lambs, it can be added up to 20% in the concentrated portion of the ration.(AU)
Assuntos
Animais , Masculino , Ovinos/crescimento & desenvolvimento , Indústria Cervejeira , Resíduos Industriais , Ração Animal/análiseRESUMO
Obesity is associated with several metabolic and endocrine disorders; and changes in plasma concentrations, secretion patterns, and clearance of various hormones are observed in obese patients. In this context, recent research has shown that overweight can influence the function of the thyroid gland, usually leading to increased thyrotropin concentrations and changes in the ratio between the hormones triiodothyronine and thyroxine, though within the normal range. The etiology of these changes is still unclear; however, several mechanisms have been proposed including the adaptive process to increase energy expenditure, hyperleptinemia, changes in the activity of deiodinases, the presence of thyroid hormones resistance, chronic low-grade inflammation, and insulin resistance. Although the clinical implications have not been clarified, studies suggest that these changes in the thyroid function of obese individuals may contribute to the worsening of metabolic complications and the development of diseases in the thyroid gland.
Assuntos
Obesidade/patologia , Obesidade/fisiopatologia , Glândula Tireoide/patologia , Glândula Tireoide/fisiopatologia , Metabolismo Energético , Humanos , Inflamação/patologia , Resistência à Insulina , Hormônios Tireóideos/metabolismoRESUMO
The common nonsynonymous variant rs16969968 in the α5 nicotinic receptor subunit gene (CHRNA5) is the strongest genetic risk factor for nicotine dependence in European Americans and contributes to risk in African Americans. To comprehensively examine whether other CHRNA5 coding variation influences nicotine dependence risk, we performed targeted sequencing on 1582 nicotine-dependent cases (Fagerström Test for Nicotine Dependence score⩾4) and 1238 non-dependent controls, with independent replication of common and low frequency variants using 12 studies with exome chip data. Nicotine dependence was examined using logistic regression with individual common variants (minor allele frequency (MAF)⩾0.05), aggregate low frequency variants (0.05>MAF⩾0.005) and aggregate rare variants (MAF<0.005). Meta-analysis of primary results was performed with replication studies containing 12 174 heavy and 11 290 light smokers. Next-generation sequencing with 180 × coverage identified 24 nonsynonymous variants and 2 frameshift deletions in CHRNA5, including 9 novel variants in the 2820 subjects. Meta-analysis confirmed the risk effect of the only common variant (rs16969968, European ancestry: odds ratio (OR)=1.3, P=3.5 × 10(-11); African ancestry: OR=1.3, P=0.01) and demonstrated that three low frequency variants contributed an independent risk (aggregate term, European ancestry: OR=1.3, P=0.005; African ancestry: OR=1.4, P=0.0006). The remaining 22 rare coding variants were associated with increased risk of nicotine dependence in the European American primary sample (OR=12.9, P=0.01) and in the same risk direction in African Americans (OR=1.5, P=0.37). Our results indicate that common, low frequency and rare CHRNA5 coding variants are independently associated with nicotine dependence risk. These newly identified variants likely influence the risk for smoking-related diseases such as lung cancer.
Assuntos
Negro ou Afro-Americano/genética , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Receptores Nicotínicos/genética , Tabagismo/etnologia , Tabagismo/genética , População Branca/genética , Adulto , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Down syndrome (DS) is one of the most common chromosomal abnormalities. Delays in cognitive development are found in the first years of life. As years pass, it may turn into intellectual deficiencies that unfold into several aspects, including difficulty recognizing emotional facial expressions. The present study investigated the recognition of six universal facial emotional expressions in a population of children aged 6-11 years who were divided into two groups: DS group and typically developing children (TDC) group. We used the Perception Test of Facial Emotional Expressions (Teste de Percepção de Emoções Faciais; TEPEF) and Wechsler Intelligence Scale for Children (WISC-III) and found that children with DS presented alterations in the recognition of expressions of disgust, surprise, and fear, whereas the recognition of happiness, sadness, and anger was maintained at a level comparable to the TDC group. Participants with DS presented significant positive correlations between sadness and Picture completion, Mazes, Arithmetic, Vocabulary, Digits, Verbal IQ, Verbal Comprehension Index, and Working Memory Index. All other facial expressions showed significant negative correlations with the Intelligence Quotient and WISC-III factorial index subtests. Absence of correlations was found among the TEPEF's six facial expressions and Information, Coding, Symbols, and Working Memory Index. The contribution of this study is related to understanding the characteristics of the recognition of facial emotions in children with DS, an important component of social relationships with their peers, schools, and families...
Assuntos
Humanos , Masculino , Feminino , Criança , Cognição , Síndrome de Down , Emoções , Expressão Facial , Percepção VisualRESUMO
Down syndrome (DS) is one of the most common chromosomal abnormalities. Delays in cognitive development are found in the first years of life. As years pass, it may turn into intellectual deficiencies that unfold into several aspects, including difficulty recognizing emotional facial expressions. The present study investigated the recognition of six universal facial emotional expressions in a population of children aged 6-11 years who were divided into two groups: DS group and typically developing children (TDC) group. We used the Perception Test of Facial Emotional Expressions (Teste de Percepção de Emoções Faciais; TEPEF) and Wechsler Intelligence Scale for Children (WISC-III) and found that children with DS presented alterations in the recognition of expressions of disgust, surprise, and fear, whereas the recognition of happiness, sadness, and anger was maintained at a level comparable to the TDC group. Participants with DS presented significant positive correlations between sadness and Picture completion, Mazes, Arithmetic, Vocabulary, Digits, Verbal IQ, Verbal Comprehension Index, and Working Memory Index. All other facial expressions showed significant negative correlations with the Intelligence Quotient and WISC-III factorial index subtests. Absence of correlations was found among the TEPEF's six facial expressions and Information, Coding, Symbols, and Working Memory Index. The contribution of this study is related to understanding the characteristics of the recognition of facial emotions in children with DS, an important component of social relationships with their peers, schools, and families.(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Síndrome de Down , Expressão Facial , Emoções , Cognição , Percepção VisualRESUMO
Este trabalho objetivou identificar a importância de plantas medicinais como primeira linha de ação para enfermidades em população residente no território da Estratégia Saúde da Família (ESF) de Montes Claros/MG, Brasil. A pesquisa foi transversal e descritiva, realizada em 2010, sendo a coleta de dados obtida por questionário semi-estruturado. O cálculo amostral do cenário do estudo embasou-se no número de famílias da ESF. O tratamento estatístico considerou o nível de significância p<0,05. Para cada família (N=253) foi entrevistada uma pessoa. Dos entrevistados, 75,5 % utilizam plantas medicinais; sem associação com renda, cor de pele, escolaridade e sexo (p>0,05). Quase a metade dos entrevistados (45,1 %) informou que utiliza mais de uma planta por vez. No caso de doença, após consulta e prescrição médica, uma parcela importante dos usuários de plantas (48,7 %) usa apenas o medicamento alopático. Concluiu-se que a utilização de plantas medicinais como recurso terapêutico independe de escolaridade e renda familiar, sugerindo incorporação cultural da prática integrativa na comunidade nortemineira estudada.
This study aimed to identify the importance of medicinal plants as a first line of action when treating diseases in populations residing in the territory of the Family Health Strategy (FHS) in Montes Claros,/state of Minas Gerais, Brazil.tThis is a cross-sectional descriptive research. Data collection took place by means of a semi-structured questionnaire in 2010. The sample size calculation was based on the number of families in the FHS study setting. For statistical analysis, the significance level considered was p <0.05. One personofrom each family (253) was interviewed. Of the respondents, regardless of income, skin color, education and sex, 75.5 % stated they use medicinal plants (p> 0.05). Almost half of respondents (45.1 %) reported the use of more than one plant at a time. In the event of illness, 42.3 % reported to use medicinal plants and visit the doctor. In case of illness, after consultation and prescription, a significant portion of the plant users (48.7 %) uses only allopathic medicine.sWe concluded that the use of medicinal plants as a therapeutic resource is independent of education and income, which suggestg cultural incorporation of the integrative practice in the community studied.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Características de Residência , /estatística & dados numéricos , Plantas Medicinais/efeitos adversos , Terapêutica , FitoterapiaRESUMO
BACKGROUND: Fatty liver disease (FLD) is characterized by increased intrahepatic triglyceride content with or without inflammation and is associated with obesity, and features of the metabolic syndrome. Several recent genome-wide association studies have reported an association between single-nucleotide polymorphism rs738409 in the (patatin-like phospholipase domain-containing protein 3) PNPLA3 gene and FLD. Liver attenuation (LA; hounsfield units, HU) by computed tomography is a non-invasive measure of liver fat, with lower values of HU indicating higher liver fat content. Clinically, a LA value of îº40 HU indicates moderate-to-severe hepatic steatosis. OBJECTIVE: We investigated whether missense rs738409 PNPLA3 interacted with abdominal visceral adipose tissue (VAT) volume (cm) to reduce LA (that is, increased liver fat) in 1019 European American men and 1238 European American women from the Family Heart Study. METHODS: We used linear regression to test the additive effect of genotype, abdominal VAT, and their multiplicative interaction on LA adjusted for age, body mass index, high-density lipoprotein-cholesterol, insulin resistance, serum triglycerides, abdominal subcutaneous adipose tissue and alcohol intake. RESULTS: In men and women combined, the interaction between each copy of the rs738409 variant allele (minor allele frequency 0.23) and 100 cm/150 mm slice VAT decreased LA by 2.68±0.35 HU (P<0.01). The interaction of 100 cm VAT and the variant allele was associated with a greater decrease in LA in women than men (-4.8±0.6 and -2.2±0.5 HU, respectively). CONCLUSIONS: The interaction between genotype and VAT volume suggest key differences in the role of PNPLA3 genotype in conjunction with abdominal VAT in liver fat accrual. The stronger association of the PNPLA3 genotype and liver fat in women suggests that women may be more sensitive to liver fat accumulation in the setting of increased visceral fat, compared with men. The presence of the PNPLA3 variant genotype, particularly in the context of high VAT content may have an important role in FLD.
Assuntos
Fígado Gorduroso/patologia , Gordura Intra-Abdominal/patologia , Lipase/genética , Fígado/patologia , Proteínas de Membrana/genética , Obesidade/patologia , Gordura Subcutânea Abdominal/patologia , Consumo de Bebidas Alcoólicas/epidemiologia , Índice de Massa Corporal , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Resistência à Insulina/genética , Gordura Intra-Abdominal/diagnóstico por imagem , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , National Heart, Lung, and Blood Institute (U.S.) , Obesidade/diagnóstico por imagem , Obesidade/epidemiologia , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Radiografia , Gordura Subcutânea Abdominal/diagnóstico por imagem , Triglicerídeos/sangue , Estados Unidos/epidemiologiaRESUMO
Justicia pectoralis (Acanthaceae) is used as an antiinflammatory, antimicrobial and bronchodilator, and its extract exerts an anxiolytic-like effect profile in animal models. This work presents the behavioral effects of an aqueous standardized extract of Justicia pectoralis (SEJP) in animal models, such as the elevated plus maze (EPM), light/dark, open field, rota rod and pentobarbital sleep time. The extract was administered intragastrically to male mice at single doses of 50, 100 and 200 mg/kg, while diazepam 1 or 2 mg/kg was used as a standard drug and flumazenil 2.5 mg/kg was used to evaluate the participation of benzodiazepinic receptors. The results showed that, similar to diazepam (1 mg/kg), SEJP significantly modified all the observed parameters in the EPM test, without altering the general motor activity in the open field, rota rod and pentobarbital sleep time tests. Flumazenil reversed not only the diazepam effect but also the SEJP effect. In the same way, all doses of SEJP increased the time of permanence in the light box in the light/dark test. The results showed that SEJP presented an anxiolytic-like effect, disproving sedative effects.
Assuntos
Acanthaceae/química , Ansiolíticos/farmacologia , Extratos Vegetais/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , CamundongosRESUMO
Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter- and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.
Assuntos
Distrofia Muscular Animal/patologia , Fenótipo , Animais , Modelos Animais de Doenças , Cães , Músculo Esquelético/patologiaRESUMO
The present study aimed to evaluate the renal and hepatic responses in eight dogs with visceral leishmaniasis submitted to treatment with meglumine antimoniate and to verify the occurrence of possible side effects. Urinalysis, hepatic and renal function tests were carried out in all animals at up to seven moments. After the end of a six-month observation period, all dogs were euthanized. Before the beginning of the experiment urinary and biochemical alterations were observed in four dogs due to the changes caused by the parasite itself. These alterations included the presence of renal cells, cylindruria, proteinuria, azotemia, hyperproteinemia and hypoalbuminemia. One dog died on the third day after treatment because an aggravation of the clinical picture, probably due to the medication. During the course of the study, an increase in hepatic enzymes was verified in two animals. Sixty days after the beginning of the treatment four dogs showed remission of clinical signs. The other three were asymptomatic with persistent biochemical alterations. From these, two presented recurrence of clinical signs about 150 days after the beginning of the treatment while in the other, hyperproteinemia persisted. Meglumine antimoniate was not efficient to treat dogs with severe renal dysfunction and the side effects observed were pain at the site of injection and the probable transient hepatotoxicity, evidenced by biochemical examinations, but without the presence of clinical signs.
Assuntos
Antiprotozoários/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/metabolismo , Rim/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Fígado/efeitos dos fármacos , Meglumina/uso terapêutico , Compostos Organometálicos/uso terapêutico , Animais , Antiprotozoários/efeitos adversos , Doenças do Cão/parasitologia , Cães , Leishmaniose Visceral/tratamento farmacológico , Meglumina/efeitos adversos , Antimoniato de Meglumina , Compostos Organometálicos/efeitos adversosRESUMO
Visceral leishmaniasis in Brazil is caused by Leishmania (Leishmania) chagasi and the dog is its most important reservoir. The clinical features in dogs include loss of weight, lymphadenopathy, renal failure, skin lesions, fever, hypergammaglobulinemia, hepatosplenomegaly, anemia, and, rarely, neurological symptoms. Most infected animals develop active disease, characterized by high anti-leishmania antibody titers and depressed lymphoproliferative ability. Antibody production is not primarily important for protection but might be involved in the pathogenesis of tissue lesions. An ELISA test was used to determine if there is an association between neurological symptoms and the presence of anti-L. chagasi antibodies in cerebrospinal fluid (CSF). Thirty serum and CSF samples from symptomatic mixed breed dogs (three with neurological symptoms) from a region of high incidence of visceral leishmaniasis in Brazil were examined for antibody using total parasite antigen and anti-dog IgG peroxidase conjugate. A high level of L. chagasi antibodies was observed in sera (mean absorbance SD, 1.939 0.405; negative control, N = 20, 0.154 0.074) and CSF (1.571 0.532; negative control, N = 10, 0.0195 0.040) from all animals studied. This observation suggests that L. chagasi can cause breakdown of filtration barriers and the transfer of antibodies and antigens from the blood to the CSF compartment. No correlation was observed between antibody titer in CSF and neurological symptoms.