RESUMO
Sporothrix brasiliensis is the main species of the S. schenckii complex implicated in the zoonotic epidemics of sporotrichosis in Rio de Janeiro, Brazil. Epidemiological features have been already described, such as zoonotic transmission by cats and increased frequency of atypical clinical aspects. The involvement of the face by contact with cats is common in childhood; as a result, ophthalmic manifestations have increased. We report a case of acute dacryocystitis in a 9-year-old girl. A calmodulin-based molecular phylogeny was used to identify the agent as S. brasiliensis. This is a rare type of presentation, usually complicated with nasolacrimal duct occlusion. The patient was cured without sequelae after treatment with a low dose of saturated solution of potassium iodide and decompressive oculoplastic surgery. Therapeutic options and considerations of aetiological agents and serology are discussed.
Assuntos
Antifúngicos/administração & dosagem , Dacriocistite/microbiologia , Dermatoses Faciais/tratamento farmacológico , Iodeto de Potássio/administração & dosagem , Esporotricose/tratamento farmacológico , Doença Aguda , Criança , Terapia Combinada , Dacriocistite/tratamento farmacológico , Dacriocistorinostomia , Dermatoses Faciais/cirurgia , Feminino , Humanos , Obstrução dos Ductos Lacrimais/tratamento farmacológico , Obstrução dos Ductos Lacrimais/microbiologia , Ducto Nasolacrimal , Procedimentos de Cirurgia Plástica , Sporothrix , Esporotricose/cirurgiaRESUMO
Herein we report the synthesis and evaluation of 14 novel peptides as potential irreversible inactivators of guinea pig liver transglutaminase (TGase). These peptides were designed to resemble Cbz-L-Gln-Gly, known to be a good TGase substrate, and to include a 1,2,4-thiadiazole group. The side chain length of the amino acid residue bearing the inhibitor group was also varied in order to permit investigation of this effect. Their inactivation rate constants were measured using a direct continuous spectrophotometric method and were found to vary between 0.330 to 0.89 microM(-1) min(-1).
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Fígado/enzimologia , Transglutaminases/antagonistas & inibidores , Animais , Bioquímica/métodos , Desenho de Fármacos , Avaliação Pré-Clínica de Medicamentos , Cobaias , Cinética , Peptídeos/química , Relação Estrutura-AtividadeRESUMO
Herein, we report the results of irreversible inhibition of guinea pig liver transglutaminase (TGase) by a series of 24 novel dipeptides containing either an alpha,beta-unsaturated amide or an epoxide functional group. Their inactivation rate constants were measured using a direct continuous spectrophotometric method and were found to vary between 421 x 10(3) and 3000 x 10(3)M(-1)min(-1).
Assuntos
Amidas/farmacologia , Inibidores Enzimáticos/farmacologia , Compostos de Epóxi/farmacologia , Fígado/efeitos dos fármacos , Transglutaminases/antagonistas & inibidores , Amidas/química , Animais , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Compostos de Epóxi/química , Cobaias , Cinética , Fígado/enzimologia , Espectroscopia de Ressonância MagnéticaRESUMO
Herein we report the development of a direct and continuous spectrophotometric method for determining transglutaminase (TGase) activity by using N,N-dimethyl-1,4-phenylenediamine (DMPDA) as a gamma-glutamyl acceptor substrate and carbobenzyloxy-l-glutamylglycine (Z-Gln-Gly) as a typical peptide gamma-glutamyl donor substrate. The transamidation activity of TGase can thus be followed by monitoring the increase of absorbance of the resulting anilide product at 278 nm. The extinction coefficient of the authentic, independently synthesized anilide was determined to be epsilon = 8940 +/- 55 M(-1) cm(-1). Using this assay, we determined the apparent K(M) of DMPDA to be 0.25 mM, which compares favorably to the apparent K(M) values determined for other acceptor substrates under conditions where Z-Gln-Gly is also used as the donor substrate, such as N-acetyl-l-lysine methyl ester (9.6 mM) and methylamine (13.1 mM). Finally, the sensitivity of this assay technique was established through the measurement of irreversible inhibition constants for iodoacetamide, determined to be K(I) = 75 +/- 11 nM and k(inact) = (120 +/- 1) x 10(5) M(-1) min(-1).
Assuntos
Espectrofotometria/métodos , Transglutaminases/metabolismo , Animais , Cobaias , Indicadores e Reagentes/química , Cinética , Fígado/enzimologia , Fenilenodiaminas/química , Sensibilidade e EspecificidadeRESUMO
Although rarely encountered, tumours of the heart are now more easily and frequently diagnosed owing to the availability of non-invasive imaging methods, notably echocardiography. With echocardiography the cardiac extension of the tumour is perfectly visualized, but its connections with the mediastinum are less readily accessible. The case presented here of a female patients with a malignant lymphoma involving the heart (right ventricle and atrium, pericardium) and the mediastinum illustrates the complementary nature of echocardiography, computerized tomography and magnetic resonance imaging.