Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Ciênc. rural (Online) ; 52(1): e20201065, 2022. tab
Artigo em Inglês | LILACS-Express | LILACSEXPRESS | ID: biblio-1286046

RESUMO

ABSTRACT: The hematopoietic system changes during the pregnancy to carry fetal development and maternal needs. This study compared the hematological parameters between ewes with single and twin pregnancies during gestation, delivery, and postpartum. The experiment was conducted on 60 healthy pregnant Dorper ewes that were divided into two experimental groups: Group 1 (G1), with single pregnancies (n=30), and Group 2 (G2), with twin pregnancies (n=30). Blood samples were collected from all ewes at different times: immediately before fixed-time artificial insemination (AI); on day 30, 90, 120, 130, and 140 of pregnancy; immediately after delivery; and at 24h and 48h postpartum. Statistical analysis compared the two groups at different times (P<0.05). Mild, normocytic, and hypochromic anemia was detected in all ewes from AI time and throughout pregnancy from both groups, but did not prove to be of clinical relevance. In the peripartum stage (from the 140th day of pregnancy to 48h postpartum), the ewes with twin pregnancies (G2) exhibited higher erythrogram values and neutrophil:lymphocyte ratio than did ewes with single pregnancies (G1). This indicated a greater hematopoietic adaptation in the body during the development of two fetuses. Except for the eosinophil numbers, all leukogram parameters were influenced by pregnancy in a similar way in both groups, and was characterized mainly by leukocytosis with neutrophilia during peripartum due to the high presence of endogenous cortisol at delivery. Thus, these findings showed that pregnancy was a stressful physiological event that increased the leukocyte count with a slight alteration in the erythrogram of Dorper ewes.


RESUMO: O sistema hematopoiético sofre mudanças durante a gestação para atender o desenvolvimento fetal e as necessidades maternas. Este estudo comparou os parâmetros hematológicos entre ovelhas com gestação simples e gemelar durante a prenhez, parto e pós-parto. O estudo foi realizado em 60 ovelhas Dorper prenhes, saudáveis, divididas em dois grupos experimentais: Grupo 1 (G1) com gestação simples (n = 30); e Grupo 2 (G2) com gestação gemelar (n = 30). Amostras de sangue foram colhidos de todas as ovelhas em diferentes momentos: imediatamente antes da inseminação artificial em tempo fixo (IA); nos dias 30, 90, 120, 130 e 140 de gestação; imediatamente após o parto; e às 24h e 48h pós-parto. A análise estatística comparou os dois grupos nos diferentes momentos (P < 0,05). Anemia leve, normocítica e hipocrômica foi detectada desde a IA e ao longo da gestação, nas ovelhas de ambos os grupos, mas não houve relevância clínica. Na fase periparto (do 140º dia de gestação às 48h pós-parto), as ovelhas com gestação gemelar (G2) mostraram valores do eritrograma e proporção neutrófilos: linfócitos mais elevados do que as ovelhas com gestação simples (G1). Isso indicou maior adaptação hematopoiética da ovelha para o desenvolvimento de dois fetos. Com exceção do número de eosinófilos, todos os parâmetros do leucograma foram influenciados pela gestação de forma semelhante em ambos os grupos, e foi caracterizada principalmente por leucocitose com neutrofilia no periparto devido ao alto nível de cortisol endógeno no parto. Assim, os achados mostraram que a gestação foi um evento fisiológico estressante que aumentou a contagem de leucócitos com leve alteração no eritrograma de ovelhas Dorper.

2.
Ciênc. rural (Online) ; 52(2): e20210041, 2022. tab
Artigo em Inglês | LILACS-Express | LILACSEXPRESS | ID: biblio-1286049

RESUMO

ABSTRACT: Eurytrema coelomaticum is a trematode reported in the pancreatic ducts of ruminants. It is conjectured that may cause disorders in the pancreas, as well as digestive and metabolic processes dependent on them. This study, determined if there is an impairment of exocrine pancreatic function, and correlated it with parasite burden. Pancreas, blood, and fecal samples were collected from 119 bovines at a abattoir. Stool samples were subjected to the gelatin and x-ray film digestion tests (to detect the presence of trypsin in feces). Using blood samples, the following biochemical tests were performed: amylase, lipase, glucose, fructosamine, cholesterol, triglycerides, total protein, albumin, and globulins. Analyses were correlated with pancreatic parasite burden. Cattle with a high parasitic load presented higher incidence of negative tests in both gelatin digestion and x-ray film digestion tests (P < 0.001) when compared to non-parasitized animals and those with a low parasitic load. Changes in those tests only occurred if the parasitemia was moderate or severe. The activity of the amylase and lipase enzymes was significantly higher in animals with low parasitemia (P < 0.05), compared to non-parasitized animals and with a high parasitic burden. In this study, in cases of high parasitemia, negative results were observed in both gelatin and x-ray film in the feces digestion tests. However, the low infection of E. coelomaticum, higher levels of serum amylase and lipase that also indicated loss of pancreatic exocrine functions were reported.


RESUMO: Eurytrema coelomaticum, um trematódeo de ductos pancreáticos de ruminantes. Conjectura-se que possa ocasionar transtornos nas funções pancreáticas, mais especificamente nos processos digestivos e metabólicos dependentes destas. Neste estudo, o objetivo foi determinar se há comprometimento da função pancreática exócrina, correlacionado-a a carga parasitária. Foram utilizados pâncreas e respectivas amostras de sangue e fezes de 119 bovinos. As amostras de fezes foram submetidas aos testes de digestão da gelatina em tubo e digestão de filme radiográfico, ambos para detecção de tripsina nas fezes. Foram realizados os seguintes exames bioquímicos em amostras de sangue: amilase, lipase, glicemia, frutosamina, colesterol, triglicerídeos, proteínas totais, albumina e globulinas. Após isto, as análises bioquímicas foram correlacionadas com a quantidade numérica de parasitas encontrados no pâncreas (post-mortem). Houve maior quantidade de testes negativos (digestão do filme radiográfico e prova de digestão da gelatina) nos animais com alta carga parasitária (P < 0.001), quando comparados aos animais não parasitados e com baixa carga parasitária. Portanto, os exames supracitados se alteram somente se a quantidade de parasitas for moderada ou severa. As atividades das enzimas amilase e lipase foram significativamente maiores nos animais que apresentavam baixa parasitemia (P < 0.05), em comparação com os animais com alta carga parasitária e não parasitados. Conclui-se que em quadros de alta parasitemia há alteração significativa nos testes de digestão nas fezes, e que em quadros de baixa parasitemia há alterações significativas nos valores de amilase e lipase séricas, ambos comprovando alterações pancreáticas importantes, de acordo com o quadro de parasitemia.

3.
Nat Commun ; 12(1): 5006, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408135

RESUMO

Obesity is a strong risk factor for cancer progression, posing obesity-related cancer as one of the leading causes of death. Nevertheless, the molecular mechanisms that endow cancer cells with metastatic properties in patients affected by obesity remain unexplored.Here, we show that IL-6 and HGF, secreted by tumor neighboring visceral adipose stromal cells (V-ASCs), expand the metastatic colorectal (CR) cancer cell compartment (CD44v6 + ), which in turn secretes neurotrophins such as NGF and NT-3, and recruits adipose stem cells within tumor mass. Visceral adipose-derived factors promote vasculogenesis and the onset of metastatic dissemination by activation of STAT3, which inhibits miR-200a and enhances ZEB2 expression, effectively reprogramming CRC cells into a highly metastatic phenotype. Notably, obesity-associated tumor microenvironment provokes a transition in the transcriptomic expression profile of cells derived from the epithelial consensus molecular subtype (CMS2) CRC patients towards a mesenchymal subtype (CMS4). STAT3 pathway inhibition reduces ZEB2 expression and abrogates the metastatic growth sustained by adipose-released proteins. Together, our data suggest that targeting adipose factors in colorectal cancer patients with obesity may represent a therapeutic strategy for preventing metastatic disease.


Assuntos
Tecido Adiposo/citologia , Reprogramação Celular , Neoplasias do Colo/fisiopatologia , Células-Tronco Neoplásicas/citologia , Nicho de Células-Tronco , Tecido Adiposo/metabolismo , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Fator de Crescimento de Hepatócito/genética , Fator de Crescimento de Hepatócito/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Metástase Neoplásica , Células-Tronco/citologia , Células-Tronco/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo
4.
Gut ; 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436496

RESUMO

OBJECTIVE: Cancer stem cells are responsible for tumour spreading and relapse. Human epidermal growth factor receptor 2 (HER2) expression is a negative prognostic factor in colorectal cancer (CRC) and a potential target in tumours carrying the gene amplification. Our aim was to define the expression of HER2 in colorectal cancer stem cells (CR-CSCs) and its possible role as therapeutic target in CRC resistant to anti- epidermal growth factor receptor (EGFR) therapy. DESIGN: A collection of primary sphere cell cultures obtained from 60 CRC specimens was used to generate CR-CSC mouse avatars to preclinically validate therapeutic options. We also made use of the ChIP-seq analysis for transcriptional evaluation of HER2 activation and global RNA-seq to identify the mechanisms underlying therapy resistance. RESULTS: Here we show that in CD44v6-positive CR-CSCs, high HER2 expression levels are associated with an activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which promotes the acetylation at the regulatory elements of the Erbb2 gene. HER2 targeting in combination with phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase kinase (MEK) inhibitors induces CR-CSC death and regression of tumour xenografts, including those carrying Kras and Pik3ca mutation. Requirement for the triple targeting is due to the presence of cancer-associated fibroblasts, which release cytokines able to confer CR-CSC resistance to PI3K/AKT inhibitors. In contrast, targeting of PI3K/AKT as monotherapy is sufficient to kill liver-disseminating CR-CSCs in a model of adjuvant therapy. CONCLUSIONS: While PI3K targeting kills liver-colonising CR-CSCs, the concomitant inhibition of PI3K, HER2 and MEK is required to induce regression of tumours resistant to anti-EGFR therapies. These data may provide a rationale for designing clinical trials in the adjuvant and metastatic setting.

5.
Ciênc. rural (Online) ; 51(4): e20200068, 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1153876

RESUMO

ABSTRACT: This study determined the canal flare index (CFI) of four dog breeds using two distinct femoral regions as a reference. Thirty-five radiographs of the hip joints of Golden Retrievers (GRG), German Shepherds (GSG), Labrador Retrievers (LRG), and Rottweilers (RG) of both sexes were used. Seventy experimental units were submitted to CFI calculation. Objective (CFIob) and subjective (CFIsub) values of the CFI of each experimental unit were determined according to the anatomical reference used for the calculation. A significant difference in the CFIob between the Golden Retriever and German Shepherd breeds (1.68 ± 0.16 and 1.49 ± 0.08), and in the CFIsub between Golden Retriever, German Shepherd, and Rottweiler breeds (2.09 ± 0.31, 1.86 ± 0.11, and 1.84 ± 0.18) was reported. The subjective form of measurement showed higher values than the objective form (GRG: 2.09 ± 0.31; GSG: 1.86 ± 0.11; LRG: 2.07 ± 0.12; RG: 1.84 ± 0.18). The CFI values of each breed were similar, suggesting a certain racial pattern. A significant difference in the interobserver assessment for both CFIsub and CFIob, in all races was observed. The CFI analysis identified morphological patterns of the proximal femur in the different races. Results indicated the need for standardization of the anatomical references used to calculate the CFI because there were statistical differences among the measurements among the observers.


RESUMO: Objetivou-se determinar o canal flare index (CFI) de quatro raças específicas de cães, utilizando-se duas regiões femorais distintas como referência. Foram analisadas 35 radiografias de articulações coxofemorais de cães das raças Golden Retriever (GGR), Pastor Alemão (GPA), Labrador Retriever (GLR) e Rottweiler (GR), de ambos os sexos, configurando 70 unidades experimentais submetidas ao cálculo do CFI. Determinaram-se os valores objetivo (CFIob) e subjetivo (CFIsub) do CFI de cada unidade experimental de acordo com a referência anatômica utilizada para o cálculo. Houve diferença significativa do CFIob entre as raças Golden Retriever e Pastor Alemão (1,68 ± 0,16 e 1,49 ± 0,08), e do CFIsub entre as raças Golden Retriever, Pastor Alemão e Rottweiler (2,09 ± 0,31, 1,86 ± 0,11 e 1,84 ± 0,18). A forma subjetiva de mensuração apresentou valores maiores que a forma objetiva (GGR: 2,09 ± 0,31; GPA: 1,86 ± 0,11; GLR: 2,07 ± 0,12; GR: 1,84 ± 0,18). Os valores de CFI de cada raça se apresentaram similares, sugerindo haver determinado padrão racial. Houve diferença significativa na avaliação interobservadores, tanto do CFIsub quanto CFIob, em todas as raças. A análise do CFI identificou padrões morfológicos do fêmur proximal nas diferentes raças. Os resultados indicaram a necessidade de padronização dos referenciais anatômicos utilizados para o cálculo do CFI, uma vez que houve relevância estatística entre as diferentes mensurações entre os observadores.

6.
Mol Cancer ; 18(1): 70, 2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30927908

RESUMO

In the last decades, the role of the microenvironment in tumor progression and therapeutic outcome has gained increasing attention. Cancer-associated fibroblasts (CAFs) have emerged as key players among stromal cells, owing to their abundance in most solid tumors and their diverse tumor-restraining/promoting roles. The interplay between tumor cells and neighboring CAFs takes place by both paracrine signals (cytokines, exosomes and metabolites) or by the multifaceted functions of the surrounding extracellular matrix. Here, we dissect the most recent identified mechanisms underlying CAF-mediated control of tumor progression and therapy resistance, which include induction of the epithelial-to-mesenchymal transition (EMT), activation of survival pathways or stemness-related programs and metabolic reprogramming in tumor cells. Importantly, the recently unveiled heterogeneity in CAFs claims tailored therapeutic efforts aimed at eradicating the specific subset facilitating tumor progression, therapy resistance and relapse. However, despite the large amount of pre-clinical data, much effort is still needed to translate CAF-directed anti-cancer strategies from the bench to the clinic.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias/metabolismo , Antineoplásicos/farmacologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Progressão da Doença , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/tratamento farmacológico , Comunicação Parácrina , Transdução de Sinais , Microambiente Tumoral
7.
Front Cell Dev Biol ; 7: 16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834247

RESUMO

Notwithstanding cancer patients benefit from a plethora of therapeutic alternatives, drug resistance remains a critical hurdle. Indeed, the high mortality rate is associated with metastatic disease, which is mostly incurable due to the refractoriness of metastatic cells to current treatments. Increasing data demonstrate that tumors contain a small subpopulation of cancer stem cells (CSCs) able to establish primary tumor and metastasis. CSCs are endowed with multiple treatment resistance capabilities comprising a highly efficient DNA damage repair machinery, the activation of survival pathways, enhanced cellular plasticity, immune evasion and the adaptation to a hostile microenvironment. Due to the presence of distinct cell populations within a tumor, cancer research has to face the major challenge of targeting the intra-tumoral as well as inter-tumoral heterogeneity. Thus, targeting molecular drivers operating in CSCs, in combination with standard treatments, may improve cancer patients' outcomes, yielding long-lasting responses. Here, we report a comprehensive overview on the most significant therapeutic advances that have changed the known paradigms of cancer treatment with a particular emphasis on newly developed compounds that selectively affect the CSC population. Specifically, we are focusing on innovative therapeutic approaches including differentiation therapy, anti-angiogenic compounds, immunotherapy and inhibition of epigenetic enzymes and microenvironmental cues.

8.
Stem Cell Res Ther ; 8(1): 236, 2017 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-29058626

RESUMO

BACKGROUND: The use of stem cells, including mesenchymal stem cells (MSCs), for regenerative medicine is gaining interest for the clinical benefits so far obtained in patients. This study investigates the use of adipose autologous tissue in combination with platelet-rich plasma (PRP) to improve the clinical outcome of patients affected by systemic sclerosis (SSc). METHODS: Adipose-derived mesenchymal stem cells (AD-MSCs) and PRPs were purified from healthy donors and SSc patients. The multilineage differentiation potential of AD-MSCs and their genotypic-phenotypic features were investigated. A cytokine production profile was evaluated on AD-MSCs and PRPs from both healthy subjects and SSc patients. The adipose tissue-derived cell fraction, the so-called stromal vascular fraction (SVF), was coinjected with PRP in the perioral area of SSc patients. RESULTS: Histopathological and phenotypical analysis of adipose tissue from SSc patients revealed a disorganization of its distinct architecture coupled with an altered cell composition. Although AD-MSCs derived from SSc patients showed high multipotency, they failed to sustain a terminally differentiated progeny. Furthermore, SVFs derived from SSc patients differed from healthy donors in their MSC-like traits coupled with an aberrant cytokine production profile. Finally, the administration of PRP in combination with autologous SVF improved buccal's rhyme, skin elasticity and vascularization for all of the SSc patients enrolled in this study. CONCLUSIONS: This innovative regenerative therapy could be exploited for the treatment of chronic connective tissue diseases, including SSc.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Plasma Rico em Plaquetas/fisiologia , Medicina Regenerativa/métodos , Escleroderma Sistêmico/terapia , Tecido Adiposo/imunologia , Adulto , Idoso de 80 Anos ou mais , Antígenos CD/genética , Antígenos CD/imunologia , Diferenciação Celular , Proliferação de Células , Terapia Baseada em Transplante de Células e Tecidos/métodos , Citocinas/genética , Citocinas/imunologia , Feminino , Expressão Gênica , Humanos , Masculino , Células-Tronco Mesenquimais/imunologia , Pessoa de Meia-Idade , Neovascularização Fisiológica , Cultura Primária de Células , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Pele/patologia
9.
Ciênc. rural ; 45(5): 848-853, 05/2015. tab
Artigo em Português | LILACS-Express | LILACS | ID: lil-745846

RESUMO

O objetivo deste estudo foi analisar e comparar os registros eletrocardiográficos de 50 equinos American Miniature Horse, clinicamente saudáveis, obtidos pelos métodos convencional e computadorizado, para a padronização do método informatizado. As medidas de duração e amplitude das ondas e intervalos e frequência cardíaca foram analisadas nas derivações do plano frontal e na derivação base-ápice. Diferenças quanto à duração da onda P, foram encontradas nas derivações I e aVL, e do complexo QRS, em todas as derivações do plano frontal. Quanto à derivação base-ápice, houve diferença na duração do intervalo QT e da onda T, assim como na amplitude da onda S. Concluiu-se, portanto, que ocorre superestimação da duração do complexo QRS no método computadorizado e que, devido às diferenças inerentes de cada método, torna-se importante a utilização de valores de referência para o método computadorizado também na espécie equina.


The aim of this study was to analyze and compare electrocardiographic records of 50 horses American Miniature Horse, clinically healthy, obtained by conventional methods and computerized, to the standardization of the computerized method. The measures of duration and amplitude of waves and intervals and heart rate were analyzed in the leads of the frontal plane and base-apical lead. Differences about the duration of the P wave were found in I and aVL derivations, and QRS complex, in all derivations of the frontal plane. As for basis-apical derivation, there was no difference in the duration of the QT interval and the T wave and the amplitude of the S wave, therefore concluding that overestimation occurs in the duration of the QRS complex in computerized method and that due to inherent differences of each method, it becomes important the use of reference values for the computerized method also in the equine species.

10.
Pesqui. vet. bras ; 30(4): 328-334, abr. 2010.
Artigo em Português | LILACS | ID: lil-548892

RESUMO

Foram analisados os resultados e complicações decorrentes do emprego da técnica de biopsia pulmonar transtorácica percutânea em 20 ovinos clinicamente sadios. Os animais foram submetidos ao exame clínico seguido da biopsia com agulha semi-automática no 7º espaço intercostal direito, 5cm acima do olécrano. Foram analisados o número de tentativas para a execução do procedimento e o tamanho dos fragmentos. As amostras obtidas foram avaliadas histologicamente. Posteriormente ao abate, foi realizado o exame pos mortem para avaliação de complicações da técnica e das eventuais lesões provocadas. Entre todos os animais submetidos à biopsia apenas dois demonstraram resistência a técnica, sendo obtidos fragmentos pulmonares de 4-7mm de comprimento, com média de 1,8±1 tentativas por fragmento. As principais alterações relacionadas à técnica foram tosse, dispnéia inspiratória, elevação das freqüências cardíaca e respiratória e aumento do ruído broncobronquiolar. Ao exame post mortem observou-se hemorragia dos músculos intercostais e pleura visceral em todos os animais. Das 20 tentativas de execução da técnica, 18 obtiveram sucesso, enquanto que em duas o fígado foi equivocadamente puncionado. As amostras de tecido pulmonar foram consideradas representativas, pois foi possível a visualização de estruturas íntegras, incluindo bronquíolos e alvéolos. Podemos concluir que a biopsia pulmonar é segura e eficaz para obtenção de amostras pulmonares com fins de diagnóstico histológico.


The results and complications arising from use of the percutaneous transthoracic lung biopsy technique in 20 clinically healthy sheep were analyzed. The animals were subjected to clinical examination followed by lung biopsy with a semi-automatic needle in the 7th right intercostal space, 5cm above the olecranon. The number of attempts to implement the procedure and size of the fragments were evaluated. The samples were evaluated histologically. After the slaughter, a postmortem examination assessed the technical complications and possible injuries. Among all animals which underwent biopsy only two did not tolerate the technique. Lung fragments measuring 4-7mm were obtained by an average of 1.8 attempts per fragment. The main changes related to the procedure were cough, labored breathing, increased heart and breathing rate, and increased bronco-bronchiolar sound. The postmortem examination revealed bleeding of the intercostal muscles and visceral pleura of various extend in all lambs, and a wound up to 14mm length in the lung of two animals that did not tolerate the procedure. From 20 attempts to implement the technique, 18 were successful, while in two of them the liver was mistakenly punctured. Samples of lung tissue were representative. It was possible to visualize intact structures, including bronchioles and alveoli. It could be concluded that lung biopsy is a safe and effective procedure to obtain lung samples for histological diagnosis.


Assuntos
Animais , Biópsia por Agulha/efeitos adversos , Biópsia por Agulha/métodos , Pulmão/anatomia & histologia , Ovinos
11.
Oncol Res ; 13(1): 55-9, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12201675

RESUMO

This article describes two cases of malignant lymphoma in which the finding of a striking epithelioid granulomatosis was the main clinical manifestation at the outset of the patients' history. Despite some suggestive clinical and laboratory data, the final diagnosis of lymphoproliferative disorder was made only after repeated histological studies in both patients. Although the association between a severe granulomatous reaction and a B-cell neoplasm is rare, the latter should be taken into account as a possible primary disease. The pathogenetic mechanisms postulated by the literature as the cause of granulomatous reactions in lymphoproliferative disorders are reported and discussed in relation to the two cases.


Assuntos
Granuloma/etiologia , Linfoma não Hodgkin/patologia , Células da Medula Óssea/patologia , Células Epiteliais/patologia , Evolução Fatal , Granuloma/patologia , Humanos , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...