224 resultados para Nasal bioavailability
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The present paper colligates the notions acquired in previous investigations, already published, and new observations upon diseases of the psittacidae, liable to be confused with psittacosis of parrots. The author calls attention to the indifference with regard to this question shown by investigators, even by those who dealt with the study of this disease on the occasion of the latest outbreak of psittacosis, in flagrant contrast with the researches upon the alterations induced by pathogenic agents of other diseases transmissible to man, when these agents pass through animals or when the latter are depositaries of the virus. This remark considerably enhances the importance of the presence paper from a hygienic and epidemiologic point of view, representing moreover a contribution to general knowledge and to veterinary medicine. The researches carried out since the appearance of the latest outbreak of psittacosis,-which occurred simultaneously with an epizooty in parrots lodged in aviary of the park of Agua Branca (Directory of Animal Industry of the State São Paulo)-led to the verification of the frequent existence in these animals of various diseases liable to be confused with psittacosis. These diseases are due to two kinds of pathogenic agents: virus and bacteria. In the first group there are to be found the diseases occasioned by the virus of human psittacosis, discovered by Western, Bedson and Simpson, and the disease me with in parrots coming from traders in S. Paulo. The infections by bacteria of the genus Salmonella and by those of other genera belong to the second group. As differential characters of the two infections due to virus, delineated on the strength of notions drawn from a detailed experimental study and from the literature on this subject, the following are given: ¹ Samples of our virus were sent, for comparison, to various investigators of psittacosis. Amongst them, Prof. M. Rivers acceded to our request; he found its nature to be different from that of the virus of psittacosis studiedby him. We are very much obliged to him for the attention he paid to this verification. Virus of psittacosis - Infectiousness: man, monkey, rabbit, mouse, hen, canary. Neurotropic affinity. Inclusions: small, protoplasmic. Exsiccation: the virus has good power of preservation. Symptoms: inactivity, drowsiness, frequent diarrhoea, oculo-nasal discharge and cough, coma. Duration: 4 to 5 days. Bodily lesions: congestion of intestines, splenomegaly. Virus of S. Paulo - Infects only psittacidae, particularly those of the genus Amazona. No localization in the nervous system. Large, nuclear. Is rapidly destroyed. Inactivity, inappetency, adynamia (drooping of the wings, indifference, leaning its beak against the bars of the cage in order not to fall down); profuse diarrhoea, of whitish stools, at times enterorrhagia; prolonged coma. 2 to 8 days. Foci of yellowish necrosis in liver, spleen and lung. At times, congestion of intestines. Characteristic features common to the two viruses.-They act in great dilutions, filter through tight candles though being partly retained, are preserved under glycerine or Bedson's solution, are stable at 55°C. heat and are destroyed by physical and chemical agents. Both virus diseases are very seldom met with in psittacidae: only once, amongst numberless sick parrots, the author met with a disease of the virus differring from that of psittacosis. This disease, greatly transmissible to man, ought to be more frequent, if it were common in parrots. On the contrary, bacteria cause diseases in these animals with great frequency, presenting variable characters, from a severe epizootic form, rapidly mortal, to ambulatory or silent forms, for the most part developing towards a cure or assuming a chronic character. Amongst the bacteria which cause the infection of this group the salmonellae predominate and amongst them the bacterium discovered by Nocard, as well as a species which in the course of this study is characterized under the name of Salmonella nocardi. The author believes that in the epizooty from which Nocard isolated his bacterium there was association of the virus-disease inducing the epizooty of that epoch in Paris with the bacterial disease, as must have happened in Argentina, where the disease was transmitted to man, and Santillan, according to Barros, isolated from the sick parrots bacteria of the genus Salmonella. The diseases of the two groups, that due to virus and that due to bacteria, are differentiated: Virus-diseases - Evolution: rapid, nearly always followed by death. Symptoms: sadness, profuse diarrhoea, of whitish stools, at times enterorrhagia, complete inappetency, adynamia, indifference, prolonged coma. Clinical forms: acute and subacute. Lesions: Foci of necrosis in liver and spleen without cellular reaction around the focus, yellow liver, multiple serositis. Presence of protoplasmic or nuclear granulations. Bacteriology: Complete lack or inconstant presence of bacteria in the organs and blood. Infectiousness of the organs and blood after filtration: positive. Bacterial diseases - Varies from one week to a month or more, not always fatal. Sadness, partial inappetency, tremblings, intensive thirst, mucous or mucosanguineous diarrhoea, lack of adynamia (reacts to stimulations and moves well at any time of the disease, though showing little disposition to locomotion), soiling of feathers. Frustrate, acute, subacute and chronic. Hepatic and intestinal cogestion, foci of necrosis in liver, spleen and lung with cellular reaction around the focus. Lack of granulations. Constant presence of bacteria in the organs and blood. Negative. The analysis of the litterature shows that the characteristic features of the diseases in parrots referred to parrot psittacosis, more frequently approach the bacterial diseases here described of these animals, a hypothesis which is reinforced by the observation of the greater frequency of infections...
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1) Duas amostras de vírus capazes de produzir uma mielencefalite foram isoladas de dois camundongos brancos suíços, de criação, espontâneamente infetados, em um total de 7.000 animais examinados; uma terceira amostra foi obtida por trituração e filtração dos intestinos de camundongos aparentemente normais. 2) Foram feitas separadamente dez passagens por inoculação intra¬cerebral em camundongos jovens e adultos. Verificou-se por testes de imunidade cruzada que as três amostras eram idênticas. Prossegiu-se então nas passagens com apenas uma das amostras. 3) O poder infetante aumenta com o número de passagens: o período médio de incubação diminui e aumenta a letalidade. 4) A infecção espontânea e experimental é descrita. A doença parece ser mais comum em animais jovens. O período de incubação varia de 5 a 30 dias. Às vêzes observa-se uma fase prodromica: fraqueza, menor atividade, dificuldade em andar; geralmente surge a paralisia flácida sem sintomas prévios, na grande maioria das vêzes, nos membros posteriores. Três formas clínicas foram observadas: super-aguda, aguda e crônica. 5) Em camundongos normais o vírus pode ser demonstrado nas fezes e nos intestinos. Ele é comum no tubo digestivo e só ocasionalmente invade o sistema nervoso central, ou melhor, a encefalomielite e primàriamente uma doença do trato digestivo no qual a invasão do SNC é um acidente. 6) O vírus passa através de velas de CHAMBERLAND L3 e L5, em BER KEFED V, N e W e em filtro Seitz EK, a suspensão sendo tão ativa como antes da filtração. Conserva-se bem em glicerina a 50% pelo menos 60 dias, se guardado na geladeira. Suspensão de cérebro e medula aquecida em banho-maria a 56°C por 30 minutos perde a atividade. 7) O título variou entre 4.000 e 20.000 dmm. 8) Obteve-se infecção por inoculação intracerebral, por instilação nasal e, com menos regularidade, por inoculação intraperitoneal; a via gástrica deu sempre resultados negativos. Camundongos muito jovens são mais suscetíveis do que os adultos. 9) O vírus foi sempre isolado ate 90 dias pos-inoculação, do cérebro e da medula de camundongos com paralisia. Animais inoculados por via i.c., que permaneceram aparentemente normais, albergam o vírus no cérebro pelo menos durante 30 dias. 10) Não foi possível isolar vírus do fígado, pulmão, bago, rim e sangue de camundongos infetados por via intracerebral. 11) Camundongos que foram inoculados por via i.c. e não apresentaram sintomas de infecção, mostraram-se em geral imunes a uma posterior inoculação de vírus. Os soros de animais convalescentes apresentam anticorpos neutralizantes verificados por provas de proteção. 12) A inoculação intracerebral do vírus em macaco, coelho, cobaia e rato, todos jovens, não produziu infecção. 13) As lesões encontradas foram de poliomielencefalite aguda, com atrofia do corno anterior da medula. Ao nível da substancia cinzenta medular e cerebral encontram-se abundantes focos inflamatórios, com predominância de mononucleares, bem como em torno de numerosos vasos. Em certos pontos do cérebro, sobretudo no rinencéfalo, foram vistos focos extensos de encefalite hemorrágica. É evidente que em torno do foco e participando das infiltrações celulares, muitos elementos microgliais puderam ser reconhecidos. As meninges, especialmente a pia-máter, mostraram-se levemente alteradas e assim mesmo em focos esparsos.
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O trabalho refere as observações feitas em 1947 em um foco de leishmaniose muco-cutânea na Baixada Fluminense (Estado do Rio de Janeiro, Brasil). A existência da moléstia como uma endemia na região foi comprovada pelo encontro de 21 cicatrizes típicas, reagindo positivamente à intradermo-reação com antígeno específico, algumas datando de 5 a 15 anos. Na época dos trabalhos, entretanto, foi constatado um "surto epidêmico", o qual coincidira com uma grande derrubada florestal para fabrico de carvão vegetal. De 306 pessoas examinadas (cêrca de 50% da população local), foram encontradas 39 com lesões leishmanióticas (12,7%). Dentro e fora dos domicílios foram capturados Phlebotomus intermedius. Em 12 cães examinados foi encontrado um com diagnóstico provável da moléstia. Quinze gatos examinados mostraram-se negativos e, do mesmo modo, 28 mamíferos silvestres de pequeno porte. Dos 39 paciente, 4 tinham lesões mucosas (10,3%); 16 apresentavam lesões múltiplas (41,0%); e 19 eram mulheres (48,7%). Havia absoluta predominância das lesões nas partes descobertas do corpo. Cêrca de 1/3 dos casos era em crianças até 10 anos, atestando uma intensa transmissão domiciliária. Existiam casas com 2 a 6 enfermos. Com base nos informes dos pacientes ou responsáveis quanto ao tempo de doença (e admitindo-se um período incubativo médio de 2 meses), conclui-se que, provàvelmente, a grande maioria das infecções se dera entre julho e novembro, coincidindo com a derrubada florestal acima citada. Em 36 casos foi feita a intradermo-reação de Montenegro, obtendo-se respostas duvidosas em 2 e positivas em 34, com intensidade variável. Foram feitas 18 biópsias. Na epiderme havia hiperacantose e, freqüentement, pseudoepiteliomatose com globos córneos e microabcessos; e na derme observaram-se 2 quadros característicos: ou um infiltrado de plasmócitos predominantes, ou uma reação granulomatosa, os quais, às vêzes, se associavam. Em geral, a granulomatose ocorria nos casos mais antigos, isolada ou associada à infiltração, que predominava nos casos mais recentes da enfermidade. A granulomatose traduziria um estado hiperérgico do organismo, uma vez que os indivífuos que a apresentaram tinham maior tempo de doença e reagiam fortemente à intradermo-reação. As leishmanias nunca se mostraram muito numerosas nos cortes estudados. Em 3 paciente foi observada cura espontânea. Foram tratados 26 doentes, sendo 18 com tártaro emético, 4 com "fuadina" e 4 com ambos os remédios. O tártaro mostrou-se tóxico, embora desse resultados tão bons quanto a "fuadina". Dois paciente com lesões da mucosa nasal não se curaram completamente, não obstante terem recebido ambos os remédios. Cinco anos depois dêste inquérito contatou-se pràticamente a extinção dêste foco de leishmaniose. Durante êsse tempo tinham sido feitas aspersões domiciliárias periódicas com o DDT para combate à malária (NERY GUIMARÃES & BUSTAMANTE, 1953).
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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.
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Relatam-se, no presente trabalho, experiências feitas em hamsters visando observar a transmissão congênita do vírus da gripe. inocularam-se 151 hamsters prenhes ou acasaladas, usando-se a via parenteral ou a nasal. o vírus foi isolado em percentagens variáveis, conforme o caso, sempre acima de 50%, quer das hamsters mães, quer dos filhotes, fetos ou embriões. Observaram-se 15,2% de perturbações embrionárias ou fetais. Processou-se, infecção latente ou inaparente nos animais e os órgãos dos que foram sacrificados não revelaram alterações comuns, macroscópicas ou microscópicas.
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The authors report a case of culture-proven disseminated American muco-cutaneous leishmaniasis caused by Leishmania brasiliensis brasiliensis in an HIV positive patient. Lesions began in the oropharynx and nasal mucosa eventually spreading to much of the skin surface. The response to a short course of glucantime therapy was good.
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The future of antimalarial chemotherapy is particulary alarming in view of the spread of parasite cross-resistances to drugs that are not even structurally related. Only the availability of new pharmacological models will make it possible to select molecules with novel mechanisms of action, thus delaving resistance and allowing the development of new chemotherapeutic strategies. We reached this objective in mice. Our approach is hunged on fundamental and applied research begun in 1980 to investigate to phospholipid (PL) metabolism of intraerythrocytic Plasmodium. This metabolism is abundant, specific and indispensable for the production of Plasmodium membranes. Any drug to interfere with this metabolism blocks parasitic development. The most effective interference yet found involves blockage of the choline transporter, which supplies Plasmodium with choline for the synthesis of phosphatidylcholine, its major PL, this is a limiting step in the pathway. The drug sensitivity thereshold is much lower for the parasite, which is more dependent on this metabolism than host cells. The compounds show in vitro activity against P. falciparum at 1 to 10 nM. They show a very low toxicity against a lymphblastoid cell line, demonstrating a total abscence of correlation between growth inhibition of parasites and lymphoblastoid cells. They show antimalarial activity in vivo, in the P. berghei or P. chabaudi/mouse system, at doses 20-to 100-fold lower than their in acute toxicity limit. The bioavailability of a radiolabeled form of the product seemed to be advantageous (slow blood clearance and no significant concentration in tissues). Lastly, the compounds are inexpensive to produce. They are stable and water-soluble.
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Human nasal polyps outgrowth culture were used to study the adhesion of Pseudomonas aeruginosa to respiratory cells. By transmission electron microscopy, bacteria associated with ciliated cells were identified trapped at the extremities of cilia, usually as aggregates of several bacterial cells. They were never seen at the interciliary spaces or attached along cilia. Bacteria were also seen to adhere to migrating cells of the periphery of the outgrowth culture. Using a model of repair of wounded respiratory epithelial cells in culture, we observed that the adhesion of P. aeruginosa to migrating cells of the edges of the repairing wounds was significantly higher than the adhesion to non-migrating cells and that adherent bacteria were surrounded by a fibrocnectin-containing fibrillar material The secretion of extracellular matrix components is involved in the process of epithelium repair following injury. To investigate the molecular basis of P. aeruginosa adhesion to migrating cells, bacteria were treated with a fibronectin solution before their incubation with the respiratory cells. P. aeruginosa treatment by fibronectin significantly increased their adhesion to migrating cells. Accordingly, we hypothesize that during cell migration, fibronectin secreted by epithelial cells may favour P. aeruginosa adhesion by establishing a bridge between the bacteria and the epithelial cell receptors. Such a mechanism may represent a critical step for P. aeruginosa infection of healing injured epithelium.
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American mucocutaneous leishmaniasis is a granulomatous disease clinically characterized by ulcerated skin lesions that can regress spontaneously. A small percentage of the affected individuals can however develop a severe destruction of the nasal, oral, pharyngeal and/or laryngeal mucous membranes many years after the healing of the primary lesion. The human immune response to the infection and the possible mechanisms underlying the pathogenesis of the disease, determining either the self-healing or the development of chronic and destructive mucosal lesions, are discussed.
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A stable microbial system in the respiratory tract acts as an important defense mechanism against pathogenic microorganisms. Perturbations in this system may allow pathogens to establish. In an ecological environment such as the respiratory tract, there are many diverse factors that play a role in the establishment of the indigenous flora. In the present work we studied the normal microbial flora of different areas of the respiratory tract of mice and their evolution from the time the mice were born. Our interest was to know which were the dominant groups of microorganisms in each area, which were the first capable of colonizing and which dominated over time to be used as probiotic microorganisms. Our results show that Gram negative facultatively anaerobic bacilli and strict anaerobic microorganisms were the last ones to appear in the bronchia, while aerobic and Gram positive cocci were present in all the areas of the respiratory tract. The number of facultative aerobes and strict anaerobes were similar in the nasal passage, pharynx instilled and trachea, but lower in bronchia. The dominant species were Streptococcus viridans and Staphylococcus saprophyticcus, followed by S. epidermidis, Lactobacilli and S. cohnii I which were present on every studied days but at different proportions. This paper is the first part of a research topic investigating the protective effect of the indigenous flora against pathogens using the mice as an experimental model.
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Methicillin resistant Staphylococcus aureus (MRSA) is an organism that is frequently transmitted in hospitals and perinatal units. The MRSA is considered a public health problem in neonatology because of its strong potential for dissemination in the wards associated with high rates of morbidity and mortality. In this study we describe the bacteriological, epidemiological and molecular characteristics of MRSA isolated from anterior nares and blood cultures of newborns hospitalized in a public maternity hospital in the city of Rio de Janeiro, Brazil. The frequency of MRSA isolated from nasal swabs of newborns was 47.8% (43/90). The genetic analysis of MRSA strains from anterior nares, showed 8 different pulsed field gel electrophoresis patterns (PFGE). Upon analysis of PFGE patterns of the 12 MRSA strains isolated from blood cultures, 8 different patterns were observed, 9 (75%) strains were genetic related to nasal secretion isolates patterns. In conclusion, our data demonstrate the importance of screening of newborns for the presence of MRSA in Brazilian hospitals and the usefulness of genetic typing of these pathogen during epidemiologic studies. This should lead to a better knowledge on the significancy and spreading of MRSA in the hospitals.
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From 1997 to 1999, we identified seven human cases of infection by fourth stage larvae of Pseudoterranova decipiens in Chile. All identified larvae were coughed up by the patients. Subjects were 10-55 years old; five were female. Some patients complained of coughing, expectoration, pharyngeal pain, nausea or anal and nasal pruritus. Larvae of three patients were coughed up from 36 h to 7 days after having eaten raw (cebiche or sushi) or lightly fried fish. P. decipiens has a marine life cycle. Infective third stage larva develop to adult stage in pinniped mammals. The nematode eggs are voided with the host faeces and develop and hatch releasing third stage larvae. Some crustaceans and fish act as hosts of third stage larvae. Man is an accidental host for third or fourth stage larvae.
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The Leprosy Control Program of Antioquia, (post-elimination leprosy state of Colombia), had registered by 1999, 56 lepromatous leprosy patients and their household contacts (HHC). Our interest was to detect Mycobacterium leprae infection in these HHC. Clinical examination, acid-fast bacillary staining (AFB) in nasal secretions, and slit skin samples, IgM anti-PGL-I in serum and Lepromine A (Mitsuda) reactivity were tested. Two hundred forty eight HHC were studied, 49% were male. After clinical examination, two HHC were diagnosed as multi bacillary patients; 13% showed positive IgM anti-PGL-I titers; Mitsuda reaction (> 4 mm) was positive in 59%; AFB was negative in all samples, except in the two new patients. HHC were classified according to test results.Group 1: two new multi bacillary patients. Group 2: 15 HHC seropositive, Mitsuda-negative. Group 3: 13 HHC seropositive, Mitsuda-positive. Group 4: 130 HHC seronegative, Mitsuda-positive. Group 5: 88 HHC seronegative, Mitsuda-negative. These results are an indication that the transmission of the infection is still happening in a region considered in the post elimination phase. The two new patients represent an infection source for others contacts, and groups 2 and 3 are infected HHC that could develop the disease in future. Follow up of high risk population is necessary to achieve real elimination of leprosy.
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The sample consists of 226 skulls from the Atacameño cemetery of Coyo Oriente (639-910 AD), associated with the Tiwanaku period. The authors analyzed signs of acute trauma typically associated with violence, and the results were 12% of men and 9.9% of women displaying any type of lesion related to violence. In males, concentration of these non-lethal lesions in the nasal region (10.4%) as opposed to a random distribution over the entire skull (1.6%), suggests that the blows were struck during rituals. The cultural context of this period, with a strong ideological influence from Tiwanaku, supports the ritual hypothesis, since both the ethnographic as well as archeological records point to the existence of non-lethal violent bleeding with ritual beating to the face. Such rituals persist to this day among certain Andean populations. Among women, the most plausible hypothesis for the lesions (3.9% in the skull, 4.9% in the nasal bones, and 0.9% in the face) is domestic conflicts, since they show a random distribution. Previous studies with other Atacameño samples had indicated the same results for women.
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Recently, we generated two bacterial recombinant proteins expressing 89 amino acids of the C-terminal domain of the Plasmodium vivax merozoite surface protein-1 and the hexa-histidine tag (His6MSP1(19)). One of these recombinant proteins contained also the amino acid sequence of the universal pan allelic T-cell epitope (His6MSP1(19)-PADRE). In the present study, we evaluated the immunogenic properties of these antigens when administered via the intra-nasal route in the presence of distinct adjuvant formulations. We found that C57BL/6 mice immunized with either recombinant proteins in the presence of the adjuvants cholera toxin (CT) or the Escherichia coli heat labile toxin (LT) developed high and long lasting titers of specific serum antibodies. The induced immune responses reached maximum levels after three immunizing doses with a prevailing IgG1 subclass response. In contrast, mice immunized by intranasal route with His6MSP1(19)-PADRE in the presence of the synthetic oligonucleotides adjuvant CpG ODN 1826 developed lower antibody titers but when combined to CT, CpG addition resulted in enhanced IgG responses characterized by lower IgG1 levels. Considering the limitations of antigens formulations that can be used in humans, mucosal adjuvants can be a reliable alternative for the development of new strategies of immunization using recombinant proteins of P. vivax.