There is evidence in both human and experimental infection caused by Mycobacterium tuberculosis, that immunologic factors influence susceptibility to infection and the progress of the disease. The present study aims to evaluate the role of IFN- g upon inflammatory granulomatous response against M. bovis. To pursue that, C57BL/6 mice lacking the genes for synthesis of IFN- g (IFN- g-/-) and their wild-type counterparts (IFN- g+/+) were intravenously inoculated with M. bovis. The ability of M. bovis to survive and replicate in the liver and lungs was evaluated by counting colony-forming unit (CFU). The histopathological features of granulomatous inflammatory response in the liver and lungs were analyzed during the infection by M. bovis. Granuloma parameters such as, size (sectional area), granuloma volume, volume density, and numerical density were calculated in each point of infection. Bacillary load was higher in both organs of the animals that were IFN- g-/- than in IFN- g+/+ mice. Granulomas were observed in the IFN- g-/- mice after 30 days of infection and were detected earlier in controls (15 days of infection). Hepatic granulomas persisted in the IFN- g-/- mice, but in the IFN- g+/+ mice control of the inflammation. In conclusion, IFN- g influenced the multiplication of M. bovis, as well as modulated the granulomatous inflammation

Existen evidencias, tanto en humanos como en modelos experimentales, que factores inmunológicos influencian. durante la infección causada por la Mycobacterium tuberculosis, tanto la infección como la progresión de la enfermedad. Este estudio se propone evaluar el papel de IFN-g en la respuesta inflamatoria granulomatosa contra M. bovis. Para ello, se inocularon ratones C57BL/6 knockout para IFN- g (IFN- g-/-) y los correspondientes salvajes (IFN- g+/+) con M. bovis. Evaluamos la capacidad de la M. bovis de sobrevivir y replicarse en el hígado y pulmones mediante la cuantificación de unidades formadoras de colonias (CPU). También analizamos los aspectos histopatológicos de la respuesta inflamatoria granulomatosa en el hígado y los pulmones durante la infección con M. bovis. Para cada punto de infección, se calcularon los parámetros del granuloma, tales como el tamaño (área de sección), el volumen del granuloma, la densidad de volumen y densidad numérica. La carga bacilar fue mayor en los dos órganos estudiados procedentes de los ratones IFN- g-/-. Los granulomas de los ratones controles se detectaron a los 15 días, mientras que los de los ratones IFN-g no se detectaron hasta los 30 días post infección. Los granulomas hepáticos persistieron en los ratones IFN- g-/-. Como conclusión es posible afirmar que el IFN- g influencia la multiplicación por M. bovis, así como también modula la inflamación granulomatosa

Some unfavourable effects of malnutrition of the host on Schistosoma mansoni worm biology and structure have been reported based upon brigthfield microscopy. This paper aims to study by morphometric techniques, some morphological parameters in male and female adult worms recovered from undernourished albino mice in comparison with parasites recovered from well-fed infected mice. Undernourished animals were fed a multideficient and essentially low protein diet (RBD diet) and compared to well-fed control mice fed with the commercial diet NUVILAB. Seventy-five days post-infection with 80 cercarie (BL strain) animals were sacrificed. All adult worms were fixed in 10% formalin and stained with carmine chloride. One hundred male and 60 female specimens from each group (undernourished and control) were examined using an image system analysis Leica Quantimet 500C and the Sigma Scan Measurement System. The following morphometrical parameters were studied: body length and width, oral and ventral suckers, number and area of testicular lobes, length and width of ovary and uterine egg. For statistical analysis, the Student's t test for unpaired samples was applied. Significant differences (p < 0.05) were detected in body length and width, in parameters of suckers, uterine egg width, ovary length and area of testicular lobes, with lower values for specimens from undernourished mice. The nutritional status of the host has negative influence on S. mansoni adult worms, probably through unavailability of essential nutrients to the parasites.

Severe destruction of intrinsic cardiac nerves has been reported in experimental acute Chagas myocarditis, followed by extensive regeneration during the chronic phase of the infection. To further study this subject, the sympathetic and para-sympathetic intracardiac nerves of mice infected with a virulent Trypanosoma cruzi strain were analyzed, during acute and chronic infection, by means of histological, histochemical, morphometric and electron microscopic techniques. No evidences of destructive changes were apparent. Histochemical demonstration for acetylcholinesterase and catecholamines did not reveal differences in the amount and distribution of intracardiac nerves, in mice with acute and chronic Chagas myocarditis or in non-infected controls. Mild, probably reversible ultrastructural neural changes were occasionally present, especially during acute myocarditis. Intrinsic nerves appeared as the least involved cardiac structure during the course of experimental Chagas disease in mice.

O grau e a morfologia da degradação do colágeno foram comparativamente analisados em ratos com fibrose hepática recente (tratamento de oito semanas com tetracloreto de carbono) e tardia (igual tratamento por 12 semanas), e acompanhados após a suspensão da administração da droga. O desaparecimento da fibrose (quando quantitativamente avaliada) foi gradual e semelhante para ambos os grupos. As modificações vistas à microscopia de luz e ao microscópio eletrônico foram também semelhantes. Estes resultados inesperadamente negativos diferem de outros modelos de fibrose hepática e sugerem que o grau de agressão ao parênquima hepático seja um fator limitante da degradação da fibrose que se segue à remoção do agente causal. Assim sendo, não apenas a idade da fibrose, mas o estado geral de alteração do órgão atingido influenciam a degradação e remoção do colágeno.

The rate and morphology of collagen degradation were comparatively analyzed in rats with "early" and "late" carbon tetrachloride-induced hepatic fibrosis, during three different periods after discontinuation of the drug. Treatment with CCl4 lasted for eight weeks for the group of early fibrosis and 12 weeks for the late fibrosis group. Fibrosis gradually disappeared, but when quantitative methods were applied, the amount of collagen degradation and removal in early and late fibrosis did not reach statistical significance. The light microscope and ultrastructural changes were also qualitatively similar in both cases. Probably some long-lasting effects to the liver, induced by the drug, prevented early hepatic fibrosis from undergoing the characteristic ultrastructural changes seen during "acute" collagen degradation, as compared to other experimental models of hepatic fibrosis, after the causal agent is totally removed. Present findings suggest that not only the age of fibrosis but also the overall damage inflicted to the organ are limiting factors in the process of collagen degradation and removal.

Com o objetivo de avaliar se a retirada de maior número de fragmentos pleurais em um único sítio (A), bem como se a biópsia em um segundo sítio (B) da sua superfície, através do mesmo orifício cutâneo, acrescenta em rendimento diagnóstico aos três fragmentos habitualmente retirados, conduzimos um estudo prospectivo no Hospital Octávio Mangabeira, envolvendo 115 pacientes com indicação de biópsia pleural. Os fragmentos pleurais foram colocados em três frascos distintos: FRA1-3 = 3 primeiros fragmentos, FRA4-8 = 5 fragmentos subseqüentes e FRB1-5 = 5 fragmentos em segundo sítio da superfície pleural. Era retirada a agulha até o subcutâneo, feitas inclinação lateral e reintrodução no espaço pleural. A análise dos fragmentos provindos do FRA1-3 evidenciou granuloma em 72/92 casos de tuberculose (78,3%) e no FRA4-8 e FRB1-5, em 74/92 casos (80,5%). Em 6/92 pacientes foram encontrados pleurite inespecífica no FRA1-3 e granuloma no FRA4-8, resultando em acréscimo diagnóstico de 8,3% (6 aos 72 pacientes). Em 7/92 pacientes (7,6%) a HP foi inespecífica no sítio A e mostrou granuloma no sítio B, resultando em acréscimo diagnóstico de 9,0% (7 aos 78 pacientes). A concordância histológica intra-observador teve um índice kappa de 0,62 (0,54 a 0,70) e interobservador de 0,64 (0,56 a 0,72). Concluímos que a realização de múltiplas biópsias em dois sítios diferentes da superfície pleural diagnosticou 13 pacientes que não obteriam diagnóstico definitivo se fossem retirados apenas três fragmentos pleurais, resultando em incremento diagnóstico de 18,0% (13 aos 72 diagnosticados no FRA1-3), sendo considerado significativo do ponto de vista médico e social.

For diagnostic purposes of pleural tuberculosis, three pleural fragments are routinely obtained from a single site by needle biopsy. The objective of this study is to compare the diagnostic yield of the routine procedure with two different approaches: harvesting five fragments on a single site (A), and collection of fragments at an additional site (B); from the same cutaneous orifice, the needle was partially removed up to the subcutaneous tissue and redirected at a 45º angle. The authors performed a prospective study in 115 patients submitted to pleural biopsy. The first three pleural fragments were placed in a vial (VA1-3), the 5 subsequent fragments obtained at the same site were placed in a second vial (VA4-8), and the five fragments from the second site were placed in a third vial (VB1-5). Analysis of fragments from VA1-3 revealed granuloma in 72/92 tuberculosis cases (78.3%), whereas in fragments VA5-8 and VB1-5, granuloma was observed in 74/92 cases (80.5%). In 6/92 patients the diagnosis at VA1-3 was non-specific pleuritis, but granuloma was found in VA4-8, resulting in a diagnosis increment of 8.3% (adding six to the 72 patients). In 7/92 patients (7.6%) the histopathological examination at site A led to a non-specific result but granuloma was found at site B, leading to a diagnostic increment of 9.0% (7 to 78 patients). Histological concordance of two examinations by the same pathologist had a kappa index of 0.62 (0.54 to 0.7) whereas concordance between two different pathologists had a kappa index of 0.64 (0.56 to 0.72). The performance of multiple biopsies at two different sites at the pleural surface led to an additional diagnosis of 13 patients, i.e., an increase of 18% (13 to 72) relative to the routine procedure. Considering the low cost increase of obtaining the fragments, adoption of this method is recommended in routine pleural tuberculosis diagnosis.

Foram operadas cinqüenta ratas Wistar, adultas, separadas em seis grupos: 1, 2, 3, grupos isotado 1 e 2 e um grupo piloto. O lobo esquerdo da tireóide da rata foi dividido em três fragmentos similares e implantados no músculo esternoclidomastóideo, na raiz do mesentério e no ovário. Os tecidos implantados foram examinados histologicamente após dez, vinte e trinta dias. No grupo isolado I, depois de trinta dias a porção restante da tireóide in situ foi removida, passando a viver somente com os implantes. Para verificar aspectos funcionais, foram implantados três fragmentos da tireóide em um grupo isolado na raiz do mesentério. T3 T4 e TSH foram dosados no soro antes e após a retirada da tireóide. O exame histológico mostrou que o tecido tireóideo implantado sofria inicialmente discreta hipotrofia, retomando em seguida para os limites da normalidade. Os melhores resultados foram obtidos com o implante no mesentério. Os valores de T 3 e T 4 eram baixos e os de TSH altos. Apoiado nos resultados histológicos e hormonais, concluiu-se que no período estudado, a tireóide autotransplantada manteve sua arquitetura folicular, cumprindo a função de produzir os hormônios.

The left thyroid lobe of Wistar rats were separated into three fragments and implanted on the sternumcleidomastoid muscle, mesentery and right ovary. The implanted tissues were removed after 10, 20and 30 days and examined histologically. For each time period of transplantation ten rats were used. After 30 days the remaing thyroid tissue was removed. The animais subsequently lived with the transplants only. To verify implant function, three thyroid fragments were implanted on the mesentery in group one. The levels of T3 T4 and TSH were measured in serum before and after the surgery. Histologic examination showed mild atrophy in the beginning which subsequently returned to normality. The best results of transplantation were obtained with the implant on the mesentery. There were low T3 and T4 levels and high TSH levels. 1n conclusion, the autotransplanted thyroid gland sustained its folicular architecture and its endocrinological function, in the studied period.

Em camundongos submetidos à ligadura parcial da veia porta e infecção pelo Schistosoma mansoni, os granulomas periovulares apareceram em grande número nos pulmões, comprovando a validade do modelo de Warren. Histologicamente os granulomas eram representados por agregados celulares compactos no seio de escasso estroma. Os macrófagos (células epitelióides) e eosinófilos eram os elementos celulares predominantes, vindo em seguida os linfóticos e plasmócitos. Ultraestruturalmenle, as células do granuloma exibiam íntimo contacto de suas membranas, com varios pontos de adesão, mas sem formar estruturas juncionais mais específicas. Os granulomas formados em torno a ovos maduros tinham tamanho, forma e composição celular similares após 10, 18 ou 25 semanas de infecção. Este aspecto contrastava com o que aparecia nos granulomas hepáticos os quais exibiam a clássica modulação. Os granulomas que envolviam as paredes arteriolares exibiam proliferação muscular, endotelial, com formação de novas vias vasculares e fibrose. As diferenças morfológicas observadas nos granulomas formados em diferentes locais e órgãos apontam para a importância de se considerar fatores locais (estromais) no determinismo dos padrões das respostas inflamatórias.

Numerous pulmonary schistosome egg granulomas were present in mice submitted to partial portal vein ligation (Warren's model). The granulomas were characterized by cellular aggregations formed within alveolar tissue. Main cellular types were macrophages (epithelioid cells), eosinophils, plasma cells and lymphocytes. These cells were supported by scanty fibrous stroma and exhibited close membrane contact points amongst themselves, but without forming specialized adhesion apparatus. When granulomas involved arterial structures, proliferation of cndothelial and smooth muscle cells occurred and fibrosis associated with angiogenesis became more evident. Granulomas formed around mature eggs in the pulmonary alveolar tissue presented approximately the same size and morphology regardless of the time of infection, the latter being 10, 18 and 25 weeks after cercarial exposure. This persistence of morphological appearance suggests that pulmonary granulomas do not undergo immunological modulation, as is the case with the granulomas in the liver and, to a lesser extent, in the intestines. Probably, besides general immunological factors, local (stromal) factors play an important role in schistosomal granuloma modulation.

Em autópsias realizadas durante 20 anos em portadores de miocardite crônica chagásica parasitologicamente comprovados, foi realizada uma pesquisa exaustiva das formas tissulares do Trypanosoma cruzi nas secções histológicas de vários órgãos. Os parasitos intracelulares foram encontrados nos tecidos extracardíacos em 11 casos (55%), a saber: tubo digestivo (10 vezes), adrenal (6 vezes) e em vários outros órgãos (1 vez cada). A presença dos parasitos se associava com discreta infiltração mononuclear focal, mas, o mais das vezes, não havia qualquer alteração. O estudo mostra que as formas de multiplicação do T. cruzi tendem a se distribuir amplamente na infecção crônica, mas como são escassas, o seu encontro depende de pesquisa minuciosa. Um fato interessante é que somente no miocárdio os parasitos aparecem associados com inflamação crônica, difusa, progressiva e fibrosante.

A search for the multiplying forms of T. cruzi in extracardiac tissues from 20 autopsied cases of chronic Chagas' myocarditis resulted in 11 positive cases (55 per cent). The digestive tract was parasitized 10 times, adrenal 6 times and several other organs were affectedon single occasions. A mild mononuclear cell reaction um seen associated with the parasitism, but most of the time no changes were present. This study shows that T. cruzi amastigotes have a widespread distribution in chronic human infections but due to their scanty number, their detection depends on thorough microscopic examination. It is interesting to note that only in the myocardium did the parasites appear associated with a chronic, diffuse, active and fibrosing inflammatory reaction.