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1.
Musculoskelet Surg ; 104(3): 303-311, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31407231

RESUMO

BACKGROUND: The nonunion fracture is a relatively frequent complication in both human and veterinary medicine. Specifically, atrophic fracture nonunions are difficult to treat, with revision surgery usually providing the best prognosis. Anabolic steroids, such as nandrolone decanoate (ND), have been reported to have beneficial clinical effects on bone mass gain during osteoporosis; however, their utility in promoting regeneration in atrophic nonunions has not been documented. Our objective was to examine morphological changes induced by the ND in experimental fracture nonunion with vascular deficit in the rat model. METHODS: Fourteen adult Wistar rats had an atrophic fracture nonunion induced in the diaphysis of their left femur. Rats were allocated into two groups: control group and nandrolone decanoate group. Rats in the latter group were given nandrolone decanoate (1.5 mg/kg IM, once a week, during 4 weeks after confirmation of fracture nonunion radiographically). Radiographic and anatomopathological examination, micro-tomography and histological analysis were assessed to characterize the morphological changes promoted by the nandrolone decanoate use. RESULTS: Based on radiology, anatomopathological evaluation, computed micro-tomography and conventional microscopy, nandrolone decanoate promoted bone regeneration at the fracture nonunion site by increasing the cellularity at the fracture site. Percentage of collagen was not significantly different between groups, consistent with high-quality regenerated bone. CONCLUSION: The anabolic steroid nandrolone decanoate improved bone mass and regeneration without affecting collagen production and therefore has potential for improving outcomes for atrophic fracture nonunion.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Fraturas do Fêmur/tratamento farmacológico , Fraturas não Consolidadas/tratamento farmacológico , Decanoato de Nandrolona/uso terapêutico , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Colágeno/biossíntese , Modelos Animais de Doenças , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Fraturas não Consolidadas/diagnóstico por imagem , Fraturas não Consolidadas/patologia , Decanoato de Nandrolona/administração & dosagem , Ratos , Ratos Wistar , Microtomografia por Raio-X
2.
J Inorg Biochem ; 175: 138-147, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28753492

RESUMO

We formerly hypothesized a mechanism whereby the antimycobacterial efficiency of a set of rhodamine labelled iron chelators is improved via the rhodamine fluorophore which enhances the chelators' permeation properties through membranes. To validate our hypothesis in a cellular context and to understand the influence of the structure of the fluorophore on the chelator's uptake and distribution within macrophages we now report comparative confocal microscopy studies performed with a set of rhodamine labelled chelators. We identify the functional groups of the chelator's framework that favor uptake by macrophages and conclude that the antimycobacterial effect is strongly related with the capacity of the chelator to distribute within the host cell and its compartments, a property that is closely related with the chelators' ability to interact with membranes. The quantification of the chelators' interaction with membranes was assessed through measurement of the corresponding partition constants in liposomes. The overall results support that the compounds which are preferentially taken up are the most efficient antimycobacterial chelators and for that reason we infer that the biological activity is modulated by the structural features of the fluorophore.


Assuntos
Antibacterianos , Quelantes , Macrófagos/microbiologia , Mycobacterium avium/metabolismo , Rodaminas , Tuberculose/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Quelantes/química , Quelantes/farmacocinética , Quelantes/farmacologia , Feminino , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Rodaminas/química , Rodaminas/farmacocinética , Rodaminas/farmacologia , Tuberculose/metabolismo , Tuberculose/veterinária
3.
Arq. bras. med. vet. zootec ; 68(6): 1516-1522, nov.-dez. 2016. tab, graf, ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-827921

RESUMO

Nos últimos anos, tem-se observado um aumento no consumo de alimentos diet e light por adolescentes ou por aqueles que estão à procura de uma alimentação com baixo teor calórico, surgindo, assim, diversos edulcorantes, como o aspartame. Porém, seu consumo ainda gera polêmica, devido a muitos dados contraditórios e inconclusivos. Diante disso, objetivou-se avaliar os efeitos da suplementação de aspartame sobre ingestão alimentar, parâmetros físicos, bioquímicos e histopatológicos em 18 ratos machos da linhagem Wistar, com cinco semanas de vida (ratos jovens), tratados durante 21 dias. Os animais foram distribuídos aleatoriamente em dois grupos: grupo controle (GC) - tratados com água destilada por gavagem, e o grupo aspartame (GA) - tratados diariamente com 2mL/100g/dia de aspartame. Todos os animais receberam ração comercial (Essence(r)) e água ad libitum. O controle da ingestão alimentar foi registrado semanalmente. Foram aferidos os parâmetros físicos por meio da análise do peso corporal, da circunferência toráxica, da circunferência abdominal, do comprimento vértice-cóccix, da gordura abdominal total e do cálculo do índice de massa corporal; os parâmetros bioquímicos foram analisados por meio da glicemia, da lipoproteína de alta densidade e dos triglicerídeos; além de tais análises, foi realizado o estudo histopatológico do fígado. Durante todo o experimento, os ratos tratados com aspartame apresentaram um aumento significativo no peso corpóreo e na ingestão alimentar quando comparados ao grupo controle. Não houve diferença nas demais análises tanto físicas, quanto bioquímicas e histopatológicas comparando-se o GA com o GC (P<0,05). Com base nos resultados obtidos, é possível inferir uma maior chance de desenvolvimento da obesidade, oriunda do consumo regular desse tipo de adoçante, já que ele comprovou ser capaz de estimular o consumo de alimentos e, consequentemente, o ganho de peso corpóreo.(AU)


Recent years have seen an increase in consumption of diet and light foods by teenagers or those who are looking for a low-calorie diet, thus resulting in several sweeteners such as aspartame. However, their consumption still generates controversy due to many contradictory and inconclusive data. Thus, the aim of this study was to evaluate the effects of aspartame supplementation on dietary intake, physical, biochemical, and histopathological parameters in 18 male Wistar rats, at five weeks old (young mice) treated for 21 days. The animals were randomly assigned into two groups: control group (CG) - treated with distilled water by gavage and aspartame group (GA) - treated with 2ml/100g/day of aspartame. All animals received commercial feed (Essence (r)) and water ad libitum. The control of food intake was recorded weekly. The physical parameters were measured by analyzing the body weight, chest circumference, waist circumference, vertex-coccyx length, total abdominal fat and calculating the body mass index; biochemical parameters were analyzed by glucose, high-density lipoprotein and triglycerides. Apart from such analysis the histopathological study of the liver was conducted. Throughout the experiment the rats treated with aspartame showed a significant increase in body weight and food intake compared to the control group. There was no difference in other analyzes such physical, biochemical, and histopathological comparing GA to GC (P<0.05). From the results we can infer a greater chance of developing obesity, coming from the regular consumption of this type of sweetener, as it proved able to stimulate food intake, and hence the gain of body weight.(AU)


Assuntos
Animais , Ratos , Aspartame/análise , Ingestão de Alimentos/efeitos dos fármacos , Aumento de Peso , Padrões de Referência/análise
4.
Arq. bras. med. vet. zootec ; 68(5): 1137-1144, set.-out. 2016. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-827887

RESUMO

The aim of this study was to characterize the renal morphology and anatomical variations of the renal pedicle in domestic shorthaired cats. Dissections were performed in 40 adult cats, obtained from the necropsy unit without macroscopic renal pathology. Kidney dimensions (length, width, and thickness) and the length and origin of the renal arteries and main branches were measured. The length, width and thickness of the right kidney (cm) were 3.83±0.46, 2.42±0.22, and 2.22±0.33 in males, and 3.61±0.53, 2.28±0.38, and 2.13±0.40 in females, respectively. In the left kidney, these measures were 3.82±0.32, 2.48±0.31, and 2.37±0.32 in males, and 3.48±0.47, 2.39±0.26, and 2.15±0.34 in females, respectively. The left kidneys of males were significantly bigger than those of females. There was a positive linear correlation between the rostrum-sacral length and ellipsoid volume of the left kidney only in males. Most of the kidneys were situated ventrally between the third to fifth lumbar vertebras. The right renal artery was situated ventrally to third lumbar vertebra and the left artery to the fourth. The results of the present study contribute to the field of comparative and applied anatomy.(AU)


O objetivo deste estudo foi caracterizar a morfologia renal e as variações anatômicas do pedículo renal em gatos de pelo curto brasileiro. As dissecções foram realizadas em 40 gatos adultos, obtidos de necropsias sem evidência de patologia renal macroscópica. Medidas renais (comprimento, largura e espessura), comprimento e origem das artérias renais e ramos principais foram obtidos. O comprimento, a largura e a espessura do rim direito (cm) foram 3,83 ± 0,46, 2,42 ± 0,22 e 2,22 ± 0,33 em machos e 3,61 ± 0,53, 2,28 ± 0,38 e 2,13 ± 0,40 em fêmeas, respectivamente. No rim esquerdo, essas medidas foram 3,82 ± 0,32, 2,48 ± 0,31 e 2,37 ± 0,32 em machos e 3,48 ± 0,47, 2,39 ± 0,26 e 2,15 ± 0,34 em fêmeas, respectivamente. O rim esquerdo dos machos foi maior do que o das fêmeas. Houve correlação linear positiva entre o comprimento rostrossacral e o volume elipsoide do rim esquerdo apenas em machos. A maioria dos rins estão situados ventralmente entre a terceira e quinta vértebras lombares. A artéria renal direita está situada ventralmente na terceira vértebra lombar, e a artéria renal esquerda na quarta. Os resultados do presente estudo contribuem para a anatomia comparada e aplicada.(AU)


Assuntos
Animais , Gatos , Rim/anatomia & histologia , Rim/irrigação sanguínea , Pesos e Medidas Corporais/veterinária
5.
J Inorg Biochem ; 121: 156-66, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23384853

RESUMO

We have recently demonstrated that tripodal hexadentate chelators, based on 3-hydroxy-4-pyridinone units, can limit the access of iron to bacteria and have a significant inhibitory effect in the intramacrophagic growth of Mycobacterium avium. The results showed that the chelation of iron is a determinant although not sufficient property for antimicrobial activity. The rhodamine B isothiocyanate labelled chelator (MRH7) exhibited the strongest inhibitory activity and was identified as a lead compound since a dose response effect was observed. Significant inhibition of M. avium growth was achieved at a concentration as low as 1 µM. To identify key molecular features essential for the biological activity we designed parent hexadentate and bidentate chelators, in which different structural groups are introduced in the molecular framework. Herein, we report the work concerning three novel fluorescent chelators: a hexadentate ligand labelled with 5(6)-carboxytetramethylrhodamine (MRH8) and two 3-hydroxy-4-pyridinone fluorescent bidentate ligands labelled with rhodamine B isothiocyanate (MRB7) and 5(6)-carboxytetramethylrhodamine (MRB8). The results show that all fluorescent chelators are capable of restricting the intramacrophagic growth of M. avium and that the inhibitory effect is dependent on the fluorophore. In fact, for compounds bearing the same fluorophore the results obtained with the hexadentate or bidentate chelator (MRH7/MRB7 or MRH8/MRB8) are identical as long as the appropriate stoichiometric amount of chelator is used. The inhibitory effect of the rhodamine B isothiocyanate labelled compounds (MRH7 and MRB7) is significantly greater than that observed for the other two chelators, thus pointing out the significance of the rhodamine B isothiocyanate molecular fragment.


Assuntos
Corantes Fluorescentes/química , Quelantes de Ferro/química , Ferro/metabolismo , Mycobacterium avium/efeitos dos fármacos , Piridonas/química , Rodaminas/química , Animais , Contagem de Colônia Microbiana , Desenho de Fármacos , Corantes Fluorescentes/farmacologia , Quelantes de Ferro/síntese química , Quelantes de Ferro/farmacologia , Ligantes , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Camundongos , Camundongos Knockout , Mycobacterium avium/crescimento & desenvolvimento , Mycobacterium avium/metabolismo , Piridonas/síntese química , Piridonas/farmacologia , Rodaminas/farmacologia , Relação Estrutura-Atividade
6.
Braz. j. morphol. sci ; 29(4): 238-242, oct.-dec. 2012. ilus, graf
Artigo em Inglês | LILACS | ID: lil-665183

RESUMO

Introduction: The palmaris longus muscle it is considered one of the most variable muscles in the human body, and its agenesis is the most frequent anatomic variation. The aim of this study was to determine the prevalence of unilateral and bilateral agenesis of palmaris longus muscle for the subjects in the city of Jataí, Goiás. Material and methods: 740 subjects, 279 men and 461 women, in the age of 10-70 years old, were observed through clinical inspection in both forearms to absence of the tendon of palmaris. The data were described in percentage values and the absence of the muscle was analyzed statistically (Chi square test; P < 0.05). Results: The bilateral presence was identified in 73.5%, the absence on the left side in 7.8%, on the right in 6.5% and bilateral absence was observed in 12.2% of subjects. Among women and men the percentage values was 9.3%, 7.3%, 13.1% and 5.4%, 5%, 10.7%, respectively to agenesis in left side, in right side and bilateral agenesis. The unilateral/bilateral agenesis was more frequent in women (29.7%) than in men (21.1%; P < 0.05). Bilateral absence was 12.4% in right handed subjects and 9.1% in left handed subjects (P > 0.05). Left and right handed subjects showed absence of muscle similar in both forearms (P > 0.05). Conclusion: most subjects studied showed bilateral presence of palmaris longus muscle, the agenesis was significantly more common in women and with similar percentage in right and left handed subjects.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Anormalidades Musculoesqueléticas/etnologia , Anormalidades Musculoesqueléticas , Músculos/anatomia & histologia , Placa Palmar , Brasil
7.
Parasitol Res ; 107(5): 1163-71, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20680343

RESUMO

The proline-rich inhibitor of 31 kDa (PI31) is highly conserved through metazoan evolution, and its activity in the proteasome inhibition is well-established although the precise mechanism of inhibition is unclear. The coding DNA sequence of Schistosoma mansoni PI31 (SmPI31) was cloned, and the recombinant protein was expressed in bacterial system. The correct amino acid sequence was confirmed by mass spectrometry and circular dichroism suggests that SmPI31 contains both α-helix and non-structured regions. Inhibition assays, using the Suc-Leu-Leu-Val-Tyr-4-MCA substrate for proteasome degradation, showed that the S. mansoni proteasome may be regulated by the inhibitory activity of SmPI31. A gene expression assay using qRT-PCR at various stages during the S. mansoni life cycle has shown that SmPI31 transcripts are expressed in all studied stages, suggesting that PI31 plays an important role during the developmental processes of the parasite. In this study first evidence is presented that PI31 has a conserved structure and plays a role as proteasome inhibitor in adult worms and it is expressed through life cycle.


Assuntos
Inibidores de Cisteína Proteinase/biossíntese , Perfilação da Expressão Gênica , Inibidores de Proteassoma , Proteínas de Protozoários/biossíntese , Schistosoma mansoni/enzimologia , Animais , Dicroísmo Circular , Clonagem Molecular , Inibidores de Cisteína Proteinase/química , Inibidores de Cisteína Proteinase/genética , Expressão Gênica , Camundongos , Camundongos Endogâmicos BALB C , Conformação Proteica , Proteínas de Protozoários/química , Proteínas de Protozoários/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Schistosoma mansoni/genética
8.
Rev. bras. plantas med ; 12(1): 120-126, jan.-mar. 2010. ilus, tab
Artigo em Português | LILACS | ID: lil-578943

RESUMO

Objetivou-se com este trabalho estudar a metodologia do teste de tetrazólio para sementes de Amburana cearensis (Allemão) A.C. Smith, determinando as melhores condições de pré-umedecimento, bem como temperatura, período de coloração e concentração da solução de tetrazólio. Avaliou-se a coloração das sementes intactas e escarificadas (lixadas), ambas com tegumento, diretamente na solução de tetrazólio nas concentrações de 0,025; 0,050; 0,075 e 1 por cento a 35 e 40ºC, por 12 e 24h no escuro. Verificou-se o pré-umedecimento para retirar o tegumento utilizando-se sementes intactas e escarificadas, as quais foram imersas diretamente em água e submetidas a embebição em papel toalha e por 12, 24, 36 e 48 horas em temperaturas de 35 e 40ºC. Após a determinação do método para retirar o tegumento os embriões foram submetidas à coloração em solução de tetrazólio nas concentrações de 0,025; 0,050; 0,075 e 1 por cento. Com os resultados obtidos verificou-se a necessidade da retirada total do tegumento para que ocorra a coloração e que a temperatura de 40ºC é prejudicial para a embebição no pré-umedecimento. O teste de tetrazólio nas sementes de A. cearensis deve ser realizado com o pré-umedecimento das sementes escarificadas (lixadas) e imersas diretamente em água por 24 horas, na temperatura de 35ºC, para posterior retirada total do tegumento. E para atingir a coloração ideal os embriões devem ser imersos em solução de tetrazólio a 0,05 por cento por 3 horas, a 40ºC.


This work aimed to evaluate the methodology of tetrazolium test in Amburana cearensis (Allemão) A.C. Smith seeds, establishing the best pre-moistening conditions, as well as temperature, coloration period and tetrazolium solution concentration. The coloration of intact and scarified (sanded) seeds, both with tegument, was directly evaluated in tetrazolium solution at the concentrations of 0.025; 0.050; 0.075; and 1 percent, at 35 and 40ºC, for 12 and 24 h in the dark. Pre-moistening to remove the tegument was evaluated by using intact and scarified seeds, which were directly immersed in water and subjected to imbibition in paper towel for 12, 24, 36, and 48 h at 35 and 40ºC. After establishing the method to remove the tegument, embryos were subjected to coloration in tetrazolium solution at the concentrations of 0.025; 0.050; 0.075; and 1 percent. Based on the obtained results, the complete tegument removal is needed for coloration; besides, the temperature of 40ºC is harmful for imbibition during pre-moistening. The tetrazolium test in A. cearensis seeds should be performed including pre-moistening through direct immersion of scarified (sanded) seeds in water for 24h at 35ºC for later complete tegument removal. To achieve the ideal coloration, embryos must be immersed in tetrazolium solution at 0.05 percent for 3h at 40ºC.


Assuntos
Dipteryx/embriologia , Dipteryx/fisiologia , Sementes , Sais de Tetrazólio/química , Fenômenos Químicos/métodos , Reações Químicas/análise
9.
Braz. j. med. biol. res ; 39(3): 411-414, Mar. 2006. ilus, graf
Artigo em Inglês | LILACS | ID: lil-421369

RESUMO

Four populations in the Amazon area were selected for a comparative study of mercury-exposed and non-exposed populations: São Luiz do Tapajós, Barreiras, Panacauera, and Pindobal Grande. The highest mercury levels in human hair samples were found in São Luiz do Tapajós and Barreiras, greatly exceeding the limits established by the World Health Organization. Panacauera showed an intermediate level below 9 µg/g. This was the first comparative and simultaneous evaluation of mercury exposure in the Amazon area. Also, thanks to this type of monitoring, we were able to eliminate the uncertainties about the reference dose. On the basis of these data, we can conclude that the mercury levels detected in exposed populations of the Tapajós River basin may be dangerous not only because they are above the World Health Organization limits, but also because the simultaneous mercury detection in non-exposed populations with similar characteristics provided a valid control and revealed lower mercury levels. Our results support the importance of continuous monitoring in both exposed and non-exposed populations.


Assuntos
Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Exposição Ambiental/análise , Cabelo/química , Mercúrio/análise , Rios/química , Brasil , Monitoramento Ambiental/métodos
10.
J Clin Virol ; 20(3): 117-22, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11166658

RESUMO

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) patients exhibit alterations in the metabolism of iron that lead to increased deposition of this element in the tissues. Such alterations may underlie an increased susceptibility of AIDS patients to mycobacterial infections, namely by Mycobacterium avium. OBJECTIVES: The understanding of the role of iron metabolism during M. avium infections in mouse models may allow the design of new therapies based on the manipulation of iron stores. STUDY DESIGN: In vitro macrophage cultures and in vivo mouse studies of iron depletion and iron overload are used to assess mycobacterial multiplication and testing of the efficacy of iron depletion strategies such as the use of iron chelators. RESULTS AND CONCLUSIONS: The levels of iron loading of macrophages in vitro or in vivo affect the growth of M. avium. The currently available iron chelators have poor efficacy in depleting the macrophage iron stores and, therefore, have a poor impact on the infection. Therefore, newer drugs are required that may be used in the context of in vivo infections such as in the case of affected AIDS patients.


Assuntos
Ferro/metabolismo , Mycobacterium avium/crescimento & desenvolvimento , Tuberculose/microbiologia , Animais , Medula Óssea/metabolismo , Células Cultivadas , Dieta , Feminino , Deficiências de Ferro , Complexo Ferro-Dextran/farmacologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium avium/efeitos dos fármacos , Tuberculose/metabolismo
11.
Immunology ; 99(2): 203-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10692037

RESUMO

Control of mycobacterial growth depends on the concerted activity of different cytokines acting in different stages of the development of innate and adaptive immune responses. Tumour necrosis factor-alpha (TNF-alpha) has been shown to play a protective role in Mycobacterium avium infections. Here we assessed the growth of this mycobacterial species in wild-type mice and in mice with a genetically engineered disruption of the type I receptor for TNF-alpha (p55-KO mice). p55-KO mice infected with a low-virulence strain of M. avium exhibited a slightly delayed capacity to eliminate the micro-organisms from the liver as compared with wild-type animals. However, either the growth of this strain in the other organs studied (spleen and lung) or the growth of two other strains of M. avium with intermediate or high virulence, failed to be affected by mutation of the TNF-alpha receptor. p55-KO mice were also as protected by the administration of recombinant interleukin-12 as the heterozygous p55 +/- mice. We conclude that signalling through the type I TNF receptor plays a small role in vivo in the induction of mycobacteriostasis during M. avium infection but may improve survival during infection with virulent mycobacteria, independently of the extent of their proliferation.


Assuntos
Mycobacterium avium/crescimento & desenvolvimento , Receptores do Fator de Necrose Tumoral/imunologia , Tuberculose/imunologia , Animais , Interleucina-12/imunologia , Fígado/microbiologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/imunologia , Baço/microbiologia , Tuberculose/microbiologia
12.
J Immunol ; 162(11): 6734-9, 1999 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10352292

RESUMO

Mice genetically deficient in the inducible NO synthase gene (iNOS-/-) were used to study the role played by NO during infection by Mycobacterium avium. iNOS-/- macrophages were equally able to restrict M. avium growth in vitro following stimulation by IFN-gamma and TNF-alpha as macrophages from wild-type mice. In vivo, the infection progressed at similar rates in wild-type and NO-deficient mice during the first 2 mo of infection, but the latter mice were subsequently more efficient in clearing the mycobacteria than the former. The increased resistance of iNOS-/- mice was associated with higher IFN-gamma levels in the serum and following in vitro restimulation of spleen cells with specific Ag, increased formation of granulomas and increased survival of CD4+ T cells. We show that NO is not involved in the antimycobacterial mechanisms of M. avium-infected macrophages and, furthermore, that it exacerbates the infection by causing the suppression of the immune response to the pathogen.


Assuntos
Mycobacterium avium/crescimento & desenvolvimento , Óxido Nítrico Sintase/genética , Tuberculose/enzimologia , Tuberculose/microbiologia , Animais , Feminino , Interferon gama/biossíntese , Interferon gama/fisiologia , Macrófagos/enzimologia , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Knockout , Mycobacterium avium/imunologia , Óxido Nítrico Sintase Tipo II , Especificidade da Espécie , Tuberculose/imunologia
13.
Infect Immun ; 67(7): 3199-206, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10377091

RESUMO

Despite the antimicrobial mechanisms of vertebrate phagocytes, mycobacteria can survive within the phagosomes of these cells. These organisms use various strategies to evade destruction, including inhibition of acidification of the phagosome and inhibition of phagosome-lysosome fusion. In contrast to mycobacteria, Coxiella burnetii, the etiologic agent of Q fever, inhabits a spacious acidified intracellular vacuole which is prone to fusion with other vacuoles of the host cell, including phagosomes containing mycobacteria. The Coxiella-infected cell thus provides a unique model for investigating the survival of mycobacteria in an acidified phagosome-like compartment. In the present study, murine bone marrow-derived macrophages were infected with either Mycobacterium avium or Mycobacterium tuberculosis and then coinfected with C. burnetii. We observed that the majority of phagocytosed mycobacteria colocalized to the C. burnetii-containing vacuole, which maintained its acidic properties. In coinfected macrophages, the growth of M. avium was not impaired following fusion with the acidified vacuole. In contrast, the growth rate of M. tuberculosis was reduced in acidified vacuoles. These results suggest that although both species of mycobacteria inhibit phagosome-lysosome fusion, they may be differentially susceptible to the toxic effects of the acidic environment in the mature phagolysosome.


Assuntos
Macrófagos/microbiologia , Mycobacterium avium/fisiologia , Mycobacterium tuberculosis/fisiologia , Fagocitose , Animais , Células Cultivadas , Coxiella/fisiologia , Grânulos Citoplasmáticos/microbiologia , Concentração de Íons de Hidrogênio , Imuno-Histoquímica , Lisossomos/metabolismo , Macrófagos/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica
14.
Tuber Lung Dis ; 79(5): 321-8, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10707261

RESUMO

SETTING: Acquired immune deficiency syndrome (AIDS) patients have increased iron deposition in different tissues which may favour the growth of Mycobacterium avium, a common bacterial opportunist in these patients. OBJECTIVE: To test whether reducing the iron loads in macrophages in vitro and in vivo reduces M. avium proliferation. DESIGN: Mycobacterial proliferation was evaluated in vitro either in axenic media or cultured macrophages and in vivo in mice after manipulation of the iron status. RESULTS: Three different compounds--desferrioxamine (DFO), N,N'bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) and a 1-amino-3-(2-bipyridyl)isoquinoline derivative (VUF8514)--were found to inhibit the growth of M. avium in axenic medium. DFO and HBED were also active in inhibiting the intramacrophagic growth of M. avium, while the use of VUF8514 was prevented by its toxicity towards the host cell. Both DFO and HBED enhanced the mycobacteriostatic effect induced in bone marrow derived macrophages by interferon gamma. In vivo, an iron poor diet led to reduced M. avium proliferation whereas the intraperitoneal administration of either DFO or HBED had small effects as they impacted little on the iron status of mice. CONCLUSION: These results confirm that iron withholding is a means of inhibiting the growth of M. avium. In vitro data suggest that iron chelating compounds may be useful as adjunct therapy against M. avium, once their in vivo activity is optimized.


Assuntos
Deficiências de Ferro , Mycobacterium avium/crescimento & desenvolvimento , Animais , Células da Medula Óssea/microbiologia , Meios de Cultura , Ferro/fisiologia , Quelantes de Ferro/farmacologia , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mycobacterium avium/efeitos dos fármacos
15.
Immunology ; 95(2): 165-8, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9824471

RESUMO

In the mouse, the progression of the Mycobacterium avium infection is highly dependent on the Nramp1 gene. Strains of mice that express the Nramp1D169 allele are highly susceptible to M. avium infections, while Nramp1G169 strains of mice can control them. Recently, the Nramp1 gene has been cloned and characterized as coding a transmembrane protein, probably involved in divalent cation transport. One possible function of this protein could be the transport of iron out of the parasite-harbouring phagosome. Previous work in our lab has shown both in vitro (in macrophage cultures) and in vivo, that the growth rate of M. avium is highly dependent on the amount of iron available in the system. To try to correlate this with the Nramp1 gene function, BALB/c (susceptible) and C.D2 (resistant) congenic mice were treated for 20 days with different doses of iron-dextran, so as to induce different degrees of iron overload, and infected with M. avium 2447. Iron administration increased M. avium growth in infected organs in a dose-dependent manner at the same time as it decreased the difference in mycobacterial growth between the two mouse strains. These results indicate that an excess of iron hampers Nramp1-encoded function, strongly suggesting a direct involvement of the Nramp1-encoded protein in the transport of this cation.


Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte de Cátions , Imunidade Inata/fisiologia , Ferro/metabolismo , Proteínas de Membrana/genética , Infecções por Mycobacterium/genética , Infecções por Mycobacterium/metabolismo , Mycobacterium avium , Alelos , Animais , Transporte Biológico , Proteínas de Transporte/metabolismo , Expressão Gênica , Imunidade Inata/genética , Ferro/análise , Complexo Ferro-Dextran/administração & dosagem , Fígado/química , Macrófagos/química , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos BALB C
16.
Rev. bras. anal. clin ; 26(3): 77-80, 1994. graf
Artigo em Português | LILACS | ID: lil-269364

RESUMO

Cerca de 5 porcento da populaçäo brasileira é portadora de litíase renal, o que corresponde a cerca de 7 milhöes de litiásicos brasileiros. É uma patologia que acomete indivíduos jovens, geralmente na terceira década de vida, nos seus anos mais produtivos, além de sua recorrência ser muito elevada. Apesar do avanço no tratamento da litíase renal nos últimos anos, através de técnicas näo invasivas, estes métodos só servem para retirar o cálculo, ou seja, eliminam a consequência da doença e näo a sua causa. Desta forma, todo paciente com urolitíase ou que já apresentou cálculo e, principalmente, aquele com história de múltiplos cálculos devem submeter-se a realizaçäo de um estudo metabólico. Com este objetivo, 73 indivíduos com litíase renal recorrente foram estudados. Destes, apenas 1 (1,4 porcento) näo apresentou alteraçäo em nenhum dos parâmetros analisados. Os principais distúrbios metabólicos encontrados foram hipercalciúria, hipernatriúria, hipocitratúria, hipomagnesúria e hiperuricosúria. Este tipo de estudo é importante e o laboratório de análises clínicas contribui na elucidaçäo dos mecanismos fisiopatogênicos responsáveis pela formaçäo de cálculos e na indicaçäo de uma terapêutica mais racional, adequada e eficaz


Assuntos
Humanos , Masculino , Feminino , Citrato de Cálcio/metabolismo , Cálculos Renais/fisiopatologia , Técnicas de Laboratório Clínico , Distúrbios do Metabolismo do Cálcio/fisiopatologia , Litíase/metabolismo , Ácido Úrico/metabolismo , Magnésio/uso terapêutico , Sódio na Dieta/metabolismo
19.
Pediatria (Säo Paulo) ; 4(3): 251-6, 1982.
Artigo em Português | LILACS | ID: lil-8446

RESUMO

Apresenta-se o caso de um recem-nascido com quadro de hidropisia fetal nao imunologica. Faz-se analise das possiveis causas responsaveis ou associadas a tal situacao, bem como dos mecanismos fisiopatologicos pelos quais a hidropisia pode ocorrer. No presente caso, a causa associada a hidropisia foi malformacao intestinal (volvulo + atresia de duodeno) sendo que o mecanismo fisiopatologico nao ficou totalmente esclarecido


Assuntos
Recém-Nascido , Humanos , Feminino , Edema , Doenças do Recém-Nascido , Obstrução Intestinal
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