Subsídio ao melhor conhecimento do tifo exantemático neotrópico no Brasil: presença do virus no leite

In articles, already published, we have proved that the strain V. B. of Brazilian virus, goes through the placenta (Macacus rhesus) (1) and the apparently normal gastro-intestinal tube (1934-1937) (Canis familiaris) (2). Today we present the idea that the Brazilian virus can reach the milk of an animal even when the latter has only the unapparent disease. In former articles (**), we have shown that the goat (Capra hircus) can be an excellent reservoir of Brazilian virus, having the strain V. B. in its blood and presenting a Weil Felix reaction high and in “group”, with the disease unapparent. When the goats are bred in the laboratory, and even in some foci of the disease, they give a negative Weil Felix, being zero for all the nine strains of Proteus. In the interior of Brazil, in many localities, goats substitute cows, in supplying milk for children and adults, and in some districts goat’s milk is considered superior to cow’s milk, possessing marvellous qualities for men, women an children. Having proved, now, that goat’s milk can contain the virus even when the animal presents nothing clinically, and having also shown that this virus goes through the digestive tube apparently sound, it is easy to understand how infants-in-arms, that is, only a few months old, living in strictly domestic surroundings, can contract the disease; we have many such cases on record. Protocol of the experiments: Goat nº 2, white, January 1948. This animal had been inoculated with the V. B. strain of the Brazilian virus in June 1947, via intra-peritoneal, presenting nothing then, not even a feverish reaction. On that occasion it was not possible to isolate the virus of the blood, although the Weil Felix reaction was positive, high and in “group”. Now January 17, 1948, seven months later, the same animal was reinoculated with a semple of virus V. B. in the same manner (intra-peritoneal) two days after bringing forth two sturdy kids. The virus V. B. was obtained from guinea-pig n. 7170 whose thermic graph was as follows: Temperatura – 38,8 – 39,1 – 39,5 – 39,4 –39,8 – 40,4 – 40,2 – 40,1 - + Necropsy – Typical lesions. The spleen weighed 5 grammes. With 3c.c. of emulsion from the nervous system of this guinea-pig, we inoculated not only the goat, as also two guineapigs, number 14 and number 5. The following is the thermic graph of one: - Guinea-pig n. 14 – 38,9 – 39,1 – 39,2 – 39.2 – 40,7 – 41,0 – 40,5 – 40,4 – 40,1 - + Typical lesions. Guinea-pig n. 2 presented the following thermic graph after the infective inoculation: - 39,5 – 39,7 – 39,7 – 39,7 – 39,5 – 39,3 – 39,5 – 39,5 – 39,5 – etc. Clinically, this animal presented nothing unusual, feeding well and suckling the kids normally. The Weil Felix reaction was positive, in “group” high very similar to the reaction obtained in June 1947, with the first infective inoculation. On the third, fourth, fifth, sixth and seventh day after the infective inoculation, we took milk from the goat and inoculated male guinea-pigs via intra-celular and via intra-peritoneal, giving 5 c.c. to each animal. Guinea-pig n. 4663, inoculated with 5 c.c. of milk, via intra-muscular, taken on the third day of the infectaive inoculation, presented the following thermic graph: - 38.8 (*) – 39,1 – 39,0 – 39,1 – 40,1 – 40,1 – 40,8 (**) – 40,8 – Killed – Typical deisions (***). The virus V. B. of this goat, circulated naturally in the blood up to the third day, having passed into the milk, producing nothing in the kids, on account of the natural resistance of these animals to the disease. The Weil Felix reaction and that of Widal for the Burcellas suis, abortus and militensis were negative for the goat and the kids. It is remarkable that, even with inoculation of the living virus after a period of seven months we cannot get a real and absolute immunity of sensitive animals. We shall return to this subject later. The hart Mazama simplicicornis may be a carrier of the virus in Brasil. The experimental serum against the virus of Exanthematic neotropical typhus has not protected guinea-pigs.

Sensibility of the hamster (Cricetus auratus) to the Treponema pertenue

In two experiments, 8 Hamsters inoculated with material from yaws lesions (Treponema pertenue), developed skin lesions considered specific by their clinical and histopathological aspects and by the presence of treponemae. These lesions appeared on the scrotumm, testicle, prepuce, anus, tail, muzzle, back and hinders paws (palm surface). In the internal organs no treponemae were found in direct examinations and inoculation of brain, spleen and lymph node. The incubation period was of 35 days for the testicle, 55 days for the scrotum and 107 days for peritoneal cavity inoculation. Positive sub-inoculations were obtained. The serum reactions (Qasserman's and Kahn's) were negative in all 5 tested Hamsters. Out of 4 normal females matched to infected males two developed nasal lesions resulting from direct contact. Apparently the genital lesions hindered copulation. Hamsters are very well suited for an experimental study of yaws.

Distribuição da xantina oxidase no fígado e no sôro de rato

The localization of the xanthine oxidase (X.O.) and xanthine dehydrogenase (X.D.) activities in rat liver have been studied using separation of cytoplasmic particles into fractions by differential centrifugation. The results clearly demonstrate that practically all the enzymic activity is present in the supernatant fluid corresponding to the cell sap containing the soluble proteins of the cell. No activity could be detected for the nuclear, mitocondrial and microsomal fractions. The enzymatic activity of the mixture of the four factions was 102 per cent of that of the original homogenate. The distribution of the xanthine dehydrogenase in the protein fractions of the rat serum was accomplished in preliminary experiments by means of 50% ammonium sulphate precipitation and subsequent dialysis against water. All enzymatic activity was confined to the globulin fractions of the serum. Paper electrophoresis was performed and the protein and lipoprotein fractions determined. A method for the localization of the X.D. activity in the protein fractions separated by paper electrophoresis was developed. The results obtained suggest that xanthine dehydrogenase is localized in the globulin fractions possessing mobilities of [alpha 1], [beta] and [gamma] globulins and are probably bound to the lipoproteins.

Estudos anatômicos e histológicos sôbre a subfamília Triatominae (Heteroptera, Reduviidae): IX. parte: vaso deferente e mesadênias de Triatoma infestans

Neste trabalho descreve-se o aparelho condutor, do testículo até o ductus ejaculatorius, incluindo as glândulas anexas, do macho de Triatoma infestans. O vas deferens compõem-se de três regiões: a) parte proximal do vas deferens; b) vesícula seminalis; c) parte distal do vas deferens com uma região glândular no ponto de saída da vesícula seminalis. As partes finais do vas deferens desembocam nos lados internos de dois ramos terminais do ductus ejaculatorius. O sistema das glândulas anexas consta de 4 mesadênias. Estas são glândulas vesiculares das quais duas são ragiócrinas e duas lipócrinas. A terceira e a quarta glândula possuem a mesma formação e função, enquanto que a primeira se difere profundamente da segunda. As secreções das glândulas misturam-se num hilo de onde o líquido passa ao ductus glandularum que o conduz ao ductus ejeculatorius. Êste possui nos seus ramos terminais uma glândula mesodérmica de natureza ragiócrina (mesadênia modificada em posição extremamente distal) e uma origem ectedérmica (ectadênia modificada em posição extremamente proximal). As secreções são expulsas das vesículas glandulares por contração da musculatura das suas paredes. O transporte dos líquidos misturados, através do ductus glandularum, verifica-se por ondas peristálticas da musculatura da membrana peritoneal do próprio ducto. As glândulas não possuem válvulas. Um refluxo das secreções é evitado pelo turgor das células epiteliais dos canais condutores. O esperma, ao entrar no ductus ejaculatorius, recebe uma mistura de 5 diferentes secreções, na qual o mesmo diluido, formando, finalmente, uma suspensão. Os aspectos histológicos estão apresentados nas figuras.

Toxoplasmose em primatas não humanos: II - Tentativas de infecções experimentais em Macacca mulatta, Cebus apella e Callithrix jacchus; e pesquisa de anticorpos em várias espécies de platyrrhinus

Após uma revisão da toxoplasmose experimental em primatas não humanos, são relatadas as tentativas, sem êxito, para provocar toxoplasmose aguda e fatal em dois rhesus (Macacca mulatta), um infante e outro jovem, por inoculação e reinoculação de uma amostra humana, usando diferentes vias e doses maciças e ainda com a ministração de decametasona. Do mesmo modo, não teve sucesso a tentativa para induzir a doença fatal em um Cebus apella adulto, pela via peritoneal. Porém a toxoplasmose-infecção nesses 3 animais, foi comprovada pela elevação da temperatura (39 a 41ºC), pela positividade da reação de Sabin-Feldman (1:64 - 1:256) e pelo isolamento de toxoplasmas em camundongos inoculados com material do Cebus. Por outro lado, em um Callithrix jacchus pela inoculação peritoneal, foi provocada doença grave e fatal com focos necróticos e abundãncia de toxoplasmas no baço e fígado, e isolamento dos parasitas em camundongo. De 54 símios do Nõvo Mundo, submetidos a RSF, todos foram negativos, com exceção de um Saimiri que se mostrou positivo a 1:16 (18%). Uma análise do problema Toxoplasmose-Primatas não humanos, com o apoio na revisão da literatura e nas nossas próprias observações (ver também o trabalho anterior) permite as seguintes conclusões: em seu habitat natural os primatas não humanos não são expostos ao Toxoplasma. Isso deve estar relacionado aos hábitos arborícolas e à sua alimentação vegetariana e insetívora; b) os casos descritos de toxoplasmose natural nos símios se referem a animais de cativeiro; e, mesmo nestas condições, é excepcional a infecção espontânea dos catarrinos; c) os catarrinos apresentam, além disso uma grande resistência à indução da toxoplasmose experimental, a qual não é devida à presença de anticorpos circulantes. Essa resistência parece não ser rompida pela administração de corticosteróides; embora às vêzes o seja pela inoculação de doses maciças de toxoplasmas, e geralmente nos animais jovens; d) essa resistência é menor nos platirrinos e parece não existir nos platirrinos inferiores e nos Prosimii.

Prolongada persistência do vírus da gripe em hamsters inoculados por vias parenterais e nasal

As experiências relatadas no presente trabalho visaram observar a persistência do vírus da gripe em hamsters inoculados pelas vias subcutânea, peritoneal e nasal. Usaram-se 53 hamsters na verificação da persistência do vírus nos seus organismos a qual atingiu até um ano e cinco meses, pelo menos, numa das séries de experiências. A outra parte do trabalho consistiu em verificar a passagem do vírus, em série, de hamster a hamster. Observamo-la até o máximo de nove vezes, o que foi excepcional, notando-se passagens, na série, com resultados negativos intercalados. Para esta última parte forma usados 91 hamsters, perfazendo o total de 144 em todas as experiências realizadas.

Consideracões sobre a natureza, desenvolvimento e transmissão de Cytamoeba bacterifera Labbé, 1894 de Leptodactylus ocellatus

Com o objetivo de fornecer dados para o esclarecimento do controvertido problema da natureza de Cytamoeba bacterifera freqüentemente encontrada nos eritrócitos de Leptodactylus ocellatus, realizamos alguns testes citoquímicos. Demonstramos a presença do ácido ribonucleico e polissacarídeos não digeríveis pela ptialina em sua estrutura. Com o método de Feulgen, teste de referência para a caracterização do ácido desoxirribonucleico, obtivemos principlemnte resultados negativos; porém, um parasito com fraca e difusa positividade e algumas reações duvidosas também foram encontrados. Ao emrpegarmos o Verde Metila-Pironina, mesmo após o tratamento pela ribonuclease, e o Azul de Toluidina, também depois da ação desta enzima, não conseguimos confimar a presença de ADN. Como os elementos constituintes de C. bacterifera são minúsculos e, às vezes, não evidenciáveis, é possível que seu teor de ADN, porventura existente, seja muito pequeno e, conseqüentemente, de difícil demonstração por métodos cujos resultados são observados sob microscopia ótica, além de poder ficar facilmente encoberto por outras substâncias. Não estamos propensos a admitir uma provável natureza virótica para Cytamoeba baseados, principalmente, em alguns de seus aspectos estruturais (figs. 8, 15, 17 e 18) e na ausência de alteração no núcleo das células parasitadas. Apesar de não termos comprovado a presença de ADN, achamos possível que C. bacterifera seja um aglomerado intracitoplasmático de organismos modificados, cujas dimensões situam-se nas proximidades do limite de resolução do microscópio ótico, relacionados com as bactérias, assim como são, por exemplo, os Clamídios e as Riquétsias. Observamos o desenvolvimento de Cytamoeba em rã mantida em cativeiro por três meses e semanalmente examinada; constatamos decréscimo paulatino da parasitemia inicial e também que os seus tipos estruturais e medidas não estavam relacionadas com a etapa da infecção. Não conseguimos transmitir, por inoculação intra-peritoneal, Cytamoeba de L. ocellatus para Bufo crucifer.

Evolution of sarcoma 180 in mice treated with hyperchlorinated water

Mice treated with hyperchlorinated water (50 ppm of chlorine) and control mice, drinking tap water (1-3 ppm of chlorine) were inoculated with 2.5 x 10 [raised to the power of 6] sarcoma 180 cells, by intraperitoneal route. Tumor evolution was measured by enumeration of tumor cells in peritoneal cavity and by evaluation of weight gain at different time intervals after tumor implantation. In mice treated with excessive amounts of chlorine there was enhancement of tumor growth demonstrated by: (a) shorter incubation period and increased weight gain (ascites formation) after tumor implantation; (b) increased number of tumor cells in the peritoneal cavity 2, 3 and 4 days after tumor challenge. The number of peritoneal cells exsudated after tumor implantation was lower in mice treated with hyperchlorinated water than in controls. The tumor enhancement observed after excessive chlorine ingestion would be due to: (a) reduction of the number of peritoneal macrophages that migrate to the peritoneal cavity and (b) reduction of the tumoricidal capacity of peritonela macrophages induced by the direct effect of chlorine or by the reduction of the amount of endogenous endotoxins due to the bactericidal effect of chlorine.

Evolution of sarcoma 180 in mice infected with Trypanosoma cruzi

Mice infected with Trypanosoma cruzi were challenged with 2x10[raised to the power of 6] cells of sarcoma 180 (ascite tumor) by i.p. route, on day seven post infection. Tumor development was followed by evaluation of weight gain, by measurement of ascitic fluid produced and enumeration of tumor cells in ascitic fluid. Infected mice were more resitant to tumor development as demonstrated by reduction in ascites formation and by reduction in the number of tumor cells in ascitic fluid, at different time intervals after tumor challenge. The number of peritoneal cells exsudated after tumor inoculation was greater in infected mice than in controls. This increased resitance of mice infected with T. cruzi to tumor development could be due to the action of macrophages activated by the infection and by the action of endotoxins absorbed from the gut or produced by the own parasite.

New measurements of energy expenditure and physical activity in chronic kidney disease.

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Giant warts in a kidney transplant patient: regression with sirolimus.

Purpose: Recent reports have suggested that intraabdominal postoperative infection is associated with higher rates of overall and local recurrence and cancer-specific mortality. However, the mechanisms responsible for this association are unknown. We hypothesized that the greater inflammatory response in patients with postoperative intraabdominal infection is associated to an increase in local and systemic angiogenesis. Methods: We designed a prospective cohorts study with matched controls. Patients with postoperative intra-abdominal infection (abscess and/or anastomotic leakage) (group 1; n=17) after elective colorectal cancer resection operated on for cure were compared to patients with an uncomplicated postoperative course (group 2; n=17). IL-6 and VEGF levels were determined by ELISA in serum and peritoneal fluid at baseline, 48 hours and postoperative day 4 or at the time the peritoneal infection occurred. Results: No differences were observed in age, gender, preoperative CEA, tumor stage and location and type of procedure performed. Although there were no differences in serum IL-6 levels at 48 hours, this pro-inflammatory cytokine was higher in group 1 on postoperative day 4 (group 1: 21533 + 27900 vs. group 2: 1130 + 3563 pg/ml; p < 0.001). Serum VEGF levels were higher in group 1 on postoperative day 4 (group 1: 1212 + 1025 vs. group 2: 408 + 407 pg/ml; p < 0.01). Peritoneal fluid VEGF levels were also higher in group 1 at 48 hours (group 1: 4857 + 4384 vs. group 2: 630 + 461 pg/ml; p < 0.001) and postoperative day 4 (group 1: 32807 + 98486 vs. group 2: 1002 + 1229 pg/ml; p < 0.001). A positive correlation between serum IL-6 and VEGF serum levels was observed on postoperative day 4 (r=0.7; p<0.01). Conclusions: These results suggest that not only the inflammatory response but also the angiogenic pathways are stimulated in patients with intra-abdominal infection after surgery for colorectal cancer. The implications of this finding on long-term follow-up need to be evaluated.

In vivo kinetics of eosinophils and mast cells in experimental murine Schistosomiasis

During the schistosomiasis infection there is a [quot ]dance of the cells[quot ], varying from site to site and related to the time of infection. 1 - Eosinophil levels exhibit a bimodal pattern, with the first peak related to the egg deposition and maturation and increased Kupfferian hyperplasia; the second peak precedes the death of some adult worms; 2 - The peritoneal eosinophilic levels are inversely proportional to the blood eosinophilic levels; 3 - Eosinopoiesis in the bone marrow begins at day 40, reaching the highest levels at day 50 and coincides with hepatic eosinophilic and neutrophilic metaplasia; 4 - Peritoneal mast cell levels present a bimodal pattern similar to the blood eosinophils, and inverse to the peritoneal eosinophils. They also show a cyclic behaviour within the hepatic and intestinal granulomas. Integral analysis of the events related to the eosinophils in the blood, bone marrow, peritoneal cavity and hepatic and intestinal granulomas allows the detection of two important eosinophilic phases: the first is due to mobilization and redistribution of the marginal pool and the second originates from eosinophilic production in the bone marrow and liver. The productive phase is characterized by an increase in the number of eosinophils and monocyte/macrophages, and a decrease in neutrophils and stabilization of megakariocytes and erithroid lineages.

NLRP3 promotes inflammation-induced skin cancer but is dispensable for asbestos-induced mesothelioma.

Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.

Pseudohypoaldosteronisms, report on a 10-patient series.

BACKGROUND: Type 1 pseudohypoaldosteronism (PHA1) is a salt-wasting syndrome caused by mineralocorticoid resistance. Autosomal recessive and dominant hereditary forms are caused by Epithelial Na Channel and Mineralocorticoid Receptor mutation respectively, while secondary PHA1 is usually associated with urological problems. METHODS: Ten patients were studied in four French pediatric units in order to characterize PHA1 spectrum in infants. Patients were selected by chart review. Genetic, clinical and biochemistry data were collected and analyzed. RESULTS: Autosomal recessive PHA1 (n = 3) was diagnosed at 6 and 7 days of life in three patients presenting with severe hyperkalaemia and weight loss. After 8 months, 3 and 5 years on follow-up, neurological development and longitudinal growth was normal with high sodium supplementation. Autosomal dominant PHA1 (n = 4) was revealed at 15, 19, 22 and 30 days of life because of failure to thrive. At 8 months, 3 and 21 years of age, longitudinal growth was normal in three patients who were given salt supplementation; no significant catch-up growth was obtained in the last patient at 20 months of age. Secondary PHA1 (n = 3) was diagnosed at 11, 26 days and 5 months of life concomitantly with acute pyelonephritis in three children with either renal hypoplasia, urinary duplication or bilateral megaureter. The outcome was favourable and salt supplementation was discontinued after 3, 11 and 13 months. CONCLUSIONS: PHA1 should be suspected in case of severe hyperkalemia and weight loss in infants and need careful management. Pathogenesis of secondary PHA1 is still challenging and further studies are mandatory to highlight the link between infection, developing urinary tract and pseudohypoaldosteronism.

Burkitts's lymphoma - an atypical presentation.

BACKGROUND: In female adolescents and young adults, malignancies of the genital tract are the most frequent type of cancer, closely followed by Hodgkin's and non-Hodgkin's lymphomas. CASE PRESENTATION: We report an unusual case of sporadic Burkitt's lymphoma (BL) presenting with massive bilateral ovarian infiltration, peritoneal carcinomatosis and diffuse nodular lesions of the stomach and the intestine mimicking Krukenberg tumor. Diagnostic biopsies were obtained by endoscopy of the upper gastrointestinal tract. With intensive chemotherapy, complete remission was rapidly achieved, without life-threatening tumor lysis syndrome. CONCLUSION: Besides metastatic gastric adenocarcinoma, BL is an important differential diagnosis in adolescents presenting with Krukenberg tumor.