RESUMO
Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL-4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN-gamma, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL-4 KO animals, indicating that mediators other than IL-4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.
Assuntos
Degranulação Celular , Leishmania major/imunologia , Leishmaniose Cutânea/imunologia , Mastócitos/fisiologia , Animais , Quimiocina CCL2/biossíntese , Quimiocina CCL5/biossíntese , Suscetibilidade a Doenças , Feminino , Pé/parasitologia , Pé/patologia , Perfilação da Expressão Gênica , Interferon gama/biossíntese , Interleucina-4/biossíntese , Interleucina-4/deficiência , Leishmaniose Cutânea/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico/biossínteseRESUMO
Chronic administration of the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats causes hypertension and morphological abnormalities in the heart, consisting mainly of ventricular hypertrophy and foci of necrosis and fibrosis. Since these phenomena have usually been described with high (or moderate) doses of L-NAME, this study was undertaken to evaluate the effects of a low dose of L-NAME on arterial blood pressure, heart weight index, left ventricular weight index, amount of ventricular fibrosis, and cardiomyocyte size. Male Wistar rats received L-NAME (7.5 mg/kg per day) in the drinking water for 2, 4, and 6 months, whereas control animals received tap water alone. At this dose, L-NAME caused 90% inhibition (P<0.001) of brain NO synthase (NOS) activity. The chronic L-NAME treatment caused an approximately 15% reduction in body weight of the animals, and no death was observed. The tail-cuff pressure was markedly (P<0.01) elevated in L-NAME-treated rats. A significant (P<0.05) reduction in both heart weight index (13-20% decrease) and left ventricular weight index (20-34% decrease) at 2, 4, and 6 months of treatment was observed in L-NAME-treated rats. The cardiomyocyte size in subendocardial, subepicardial, and midmyocardial regions of the left ventricles was time-dependently reduced, irrespective of the region studied, as measured at 2 (11% decrease), 4 (28% decrease, P<0.05), and 6 (45% decrease, P<0.05) months of chronic L-NAME treatment. The amount of fibrous tissue was unaltered at 2 and 4 months, but a small (but significant) increase in the amount of fibrous tissue was detected at 6 months (7.1+/-0.2 %, P<0.05) compared to that of control animals (5.9+/-0.2%). Our results show that chronic treatment of rats with a low dose of L-NAME for prolonged periods (up to 6 months) causes arterial hypertension accompanied by significant reductions in heart weight, left ventricular weight indexes, and cardiomyocyte size.
Assuntos
Cardiomegalia/induzido quimicamente , Cardiomegalia/patologia , Inibidores Enzimáticos/toxicidade , Miocárdio/patologia , NG-Nitroarginina Metil Éster/toxicidade , Óxido Nítrico Sintase/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Fibrose/induzido quimicamente , Fibrose/patologia , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/patologia , Masculino , Miocárdio/ultraestrutura , Óxido Nítrico Sintase Tipo I , Óxido Nítrico Sintase Tipo III , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The role of adenosine on regulation of the (Na(+)+K(+))ATPase activity present in the Malpighian tubules isolated from Rhodnius prolixus was investigated. Adenosine decreases the (Na(+)+K(+)) ATPase specific activity by 88%, in a dose-dependent manner, with maximal effect at a concentration of 10(-9) M. This effect was mimicked by N(6)-cyclohexyladenosine (CHA) at 10(-8) M, an agonist for A(1) adenosine receptor, and was reversed by 10(-9) M 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an antagonist for A(1) adenosine receptor. On the other hand, 5'-N-ethyl-carboxamide adenosine (NECA), an agonist for A(2) adenosine receptor, used in the range of 10(-9)-10(-5) M, did not change the (Na(+)+K(+))ATPase specific activity. In the same way, 10(-8) M 3, 7-dimethyl-1-propargylxanthine (DMPX), an antagonist for A(2) adenosine receptor, did not modify the inhibitory effect of adenosine. These data suggest that the inhibitory effect of adenosine on the (Na(+)+K(+))ATPase specific activity present in Malpighian tubules from Rhodnius prolixus is mediated by A(1) adenosine receptor activation. Arch.
Assuntos
Adenosina/farmacologia , Túbulos de Malpighi/enzimologia , Rhodnius/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Adenosina-5'-(N-etilcarboxamida)/farmacologia , Animais , Receptores Purinérgicos P1/metabolismo , Rhodnius/efeitos dos fármacos , Teobromina/análogos & derivados , Teobromina/farmacologia , Xantinas/farmacologiaRESUMO
A new series of 1,2,4-oxadizoles 6a-g have been synthesised in good yields using the peptide synthesis strategy. The prepared compounds were tested for anti-inflammatory and antimicrobial activities. The anti-inflammatory activities were determined in the rat paw oedema induced by carrageenin. Compounds 6a, c, f and g (i.v.) significantly inhibited the rat paw oedema induced by carrageenin depending upon the dose employed. The compounds were also evaluated for their in vitro antimicrobial activity. Some compounds were found to have significant activity against Gram positive and Gram negative microorganisms.
Assuntos
Anti-Infecciosos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Oxidiazóis/química , Animais , Antibacterianos , Bactérias/efeitos dos fármacos , Carragenina , Edema/induzido quimicamente , Edema/prevenção & controle , Fungos/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Oxidiazóis/farmacologia , Ratos , Ratos WistarRESUMO
Cardiac tissue is densely innervated by sensory neurons that are believed to play important modulatory roles in cardiac functions. In this study, pretreatment of neonate rats with capsaicin was performed. In adult rats, cardiomyocyte size and amount of fibrous tissue in left ventricles as well as in vitro coronary flow were evaluated. The chronotropic and inotropic responses to beta-adrenoceptor agonists (norepinephrine and isoproterenol), muscarinic agonists (carbachol and pilocarpine), and calcitonin gene-related peptide (CGRP) were also investigated with the use of the isolated right atria preparation. Capsaicin pretreatment significantly (P<0.05) reduced both basal coronary flow (18% reduction) and cardiomyocyte size (34% reduction) without affecting the amount of fibrous tissues in the left ventricles. The positive inotropic and chronotropic effects in response to norepinephrine in the isolated rat heart did not significantly differ between control and capsaicin-treated rats. Similarly, the positive chronotropic effects in response to norepinephrine, isoproterenol, and CGRP as well as the negative chronotropic responses to carbachol and pilocarpine in the isolated right atria were not affected by capsaicin pretreatment. Our data are consistent with the suggestion that reductions of both basal coronary flow and cardiomyocyte size seen in hearts from capsaicin-pretreated rats may be consequences of CGRP depletion. The cardiomyocyte size reduction produced by capsaicin treatment may be related to a modulatory role of CGRP as a growth factor.
Assuntos
Circulação Coronária/fisiologia , Miocárdio/citologia , Neurônios Aferentes/fisiologia , Função Ventricular , Agonistas Adrenérgicos beta/farmacologia , Animais , Pressão Sanguínea , Capsaicina/farmacologia , Tamanho Celular , Ventrículos do Coração/inervação , Isoproterenol/farmacologia , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/farmacologiaRESUMO
A protective herd effect has been described after susceptible populations of children are vaccinated with conjugate Haemophilus influenzae type b (Hib). Hib carriage was studied in children aged 6-24 months attending day care centers in two cities in southern Brazil (Curitiba and Porto Alegre). In Curitiba, routine immunization with Hib polyribosylribitol phosphate polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) in combination with diphtheria-tetanus toxoids-pertussis vaccine (PRP-T/DTP) has been offered since September 1996; DTP vaccine alone is routinely given in Porto Alegre. Children in Porto Alegre (n=643) were 8 times less likely to have received adequate Hib vaccination and 4 times more likely to be Hib carriers than children in Curitiba (n=647; i.e., point prevalence of oropharyngeal colonization, 4.8% vs. 1.2%). Point prevalence of carriage with non-type b or other nontypeable Hi was similar in children of both cities. There was a vaccination effect on carriage rates in children who received a primary 3-dose series, independent of the booster dose, suggesting that a booster may be unnecessary to induce population protection.
Assuntos
Vacina contra Difteria, Tétano e Coqueluche , Vacinas Anti-Haemophilus , Haemophilus influenzae/isolamento & purificação , Orofaringe/microbiologia , Toxoide Tetânico , Vacinas Conjugadas , Brasil , Portador Sadio/microbiologia , Creches , Pré-Escolar , Etnicidade , Feminino , Haemophilus influenzae/fisiologia , Habitação , Humanos , Lactente , MasculinoRESUMO
The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Hipertensão/prevenção & controle , Isquemia Miocárdica/prevenção & controle , Óxido Nítrico/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Determinação da Pressão Arterial/métodos , Peso Corporal/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/sangue , Diltiazem/sangue , Diltiazem/farmacologia , Inibidores Enzimáticos/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , NG-Nitroarginina Metil Éster/farmacologia , Nifedipino/sangue , Nifedipino/farmacologia , Ratos , Ratos Wistar , Análise de SobrevidaRESUMO
BCG-test reaction was carried out in 91 non-tuberculous children between 2 and 11 years old, who had received BCG vaccination during the first six months of life to critically evaluate the usefulness of this test in Pediatric practice. The BCG-test profile of the vaccinated group was shown to have a unimodal distribution, varying from 3 to 17 millimeters, with a median of 6 millimeters. It was demonstrated that the degree of reaction decreases with time. Nevertheless, false-positives could be expected in a significant percentage when reactions larger than 10 millimeters are considered as a cutoff. The specificity can be increased using only reactions with diameter equal or greater than 15 millimeters as an indicator of tuberculous disease.
RESUMO
The development of resistance to antibiotics can present a major problem when treating serious bacterial infections. Resistance may be increased due to indiscriminate prescribing and variations in resistance to an antibiotic may reflect different prescribing habits. In Latin American countries, where use of antibiotics is poorly controlled, resistance to gentamicin, tobramycin and amikacin, for example, is considerably higher than that found in Europe and the USA, where tighter restrictions are imposed. It is concluded that vigilance in the prescribing of antibiotics should be observed to prevent further increases in resistance.