Mucopolysaccharidoses (MPS) are rare lysosomal disorders caused by the deficiency of specific lysosomal enzymes responsible for glycosaminoglycan (GAG) degradation. Enzyme Replacement Therapy (ERT) has been shown to reduce accumulation and urinary excretion of GAG, and to improve some of the patients' clinical signs. We studied biochemical and molecular characteristics of nine MPS patients (two MPS I, four MPS II and three MPS VI) undergoing ERT in northern Brazil. The responsiveness of ERT was evaluated through urinary GAG excretion measurements. Patients were screened for eight common MPS mutations, using PCR, restriction enzyme tests and direct sequencing. Two MPS I patients had the previously reported mutation p.P533R. In the MPS II patients, mutation analysis identified the mutation p.R468W, and in the MPS VI patients, polymorphisms p.V358M and p.V376M were also found. After 48 weeks of ERT, biochemical analysis showed a significantly decreased total urinary GAG excretion in patients with MPS I (p < 0.01) and MPS VI (p < 0.01). Our findings demonstrate the effect of ERT on urinary GAG excretion and suggest the adoption of a screening strategy for genotyping MPS patients living far from the main reference centers.

Mice genetically selected for high (H) and low (L) antibody production (Selection IV-A) were used as murine experimental model. The aim of the present work was to evaluate the macrophagic activity and to characterize the immune response in Mycobacterium bovis-AN5 infected mice (3X10(7) bacteria). The response profile previously observed in such strains was not similar to that obtained during M. bovis infection; however, it corroborated works carried out using Selection I, which is very similar to Selection IV-A regarding infection by M. tuberculosis and Bacillus Calmette-Guérin (BCG). Considering bacterial recovery, L IV-A mice showed higher control of the infectious process in the lungs than in the spleen, whereas H IV-A mice presented more resistance in the spleen. With respect to macrophagic activity, hydrogen peroxide (H2O2) was probably not involved in the infection control since there was an inhibition in the production of this metabolite. Nitric oxide (NO) and TNF-alpha production seemed to be important in the control of bacterial replication and varied according to the strain, period and organ. Evaluation of the antibody production indicated that the multi-specific effect commonly observed in these strains was not the same in the response to M. bovis. Antibody concentrations were higher in L IV-A than in H IV-A mice at the beginning of the infection, being similar afterwards. Such data were compared with delayed-type hypersensitivity (DTH), which was more intense in H IV-A than in L IV-A mice, indicating that antibody production is independent of the capability to trigger DTH reactions and that cellular and humoral responses to M. bovis antigens show a polygenic control and an independent quantitative genetic regulation. Differences were observed among organs and metabolites, suggesting that different mechanisms play an important role in this infection in natural heterogeneous populations, indicating that NO, TNF-alpha and Th1 cytokines are involved in the infection control.

The reactivity of 2-amino-5,10,15,20-tetraphenylporphyrinatonickel(II) with acryloyl and cinnamoyl chlorides was studied. The reaction with acryloyl chloride afforded the dihydro-2-pyridone fused porphyrin 3a resulting from an aza-annulation reaction. The oxidation of 3a afforded the corresponding 2-pyridone derivative. N-Acylation reaction is an important competing transformation, giving rise to amide derivatives. The structures of the novel compounds were established by NMR and mass spectrometry studies.

En el presente trabajo se estudió la reactividad de 2-amino-5,10,15,20-tetrafenilporfirinatoníquel(II) con los cloruros de acriloílo y cinamoílo. De la reacción de aza-anulación con cloruro de acriloílo resultó la porfirina 3a que posee un anillo de dihidro-2-piridona fundido. La oxidación de 3a permitió la obtención del derivado de 2-piridona correspondiente. La reacción de N-acilación es una importante transformación competitiva, que origina los derivados de amida. La estructura de los nuevos compuestos fue establecida por estudios de RMN y por Espectrometría de Masa.

O presente trabalho teve por objetivo a análise comparativa dos óleos voláteis de espécies da família Piperaceae. As espécies estudadas foram as seguintes: Piper aduncum, P. amalago, P. arboreum, P. cernuum, P. hispidum, P. regnelii, P. submarginalum, P. vicosanum e Pothomorphe umbellata. A análise dos óleos voláteis foi efetuada pela combinação de técnicas de Cromatografia de Fase Gasosa (CG) e de Cromatografia de Fase Gasosa acoplada a Espectrometria de Massa (CG/EM). A porcentagem de identificação dos constituintes nas análises dos óleos voláteis de Piper aduncum, P. amalago, P. vicosanum, P. submarginalum e Pothomorphe umbellata, atingiu valores superiores a 80%. Houve predominância de compostos de natureza sesquiterpênica nas composições químicas das espécies analisadas, com exceção de P. hispidum, P. submarginalum e P. vicosanum onde a predominância na composição foi de monoterpenos. Pelos dados apresentados observou-se que, dentre os compostos majoritários, os mais freqüentes, nas 9 espécies estudadas, foram beta-pineno (9/9) e espatulenol (9/9), seguidos por E-cariofileno (8/9), óxido de cariofileno (8/9), germacreno D (7/9), alfa-pineno (7/9) e limoneno (6/9). Pela primeira vez se relata a composição dos óleos voláteis de P. submarginalum e P vicosanum.

Essential oils from various vegetal species of the Piperaceae family were analysed by Capillary Gas Chromatography (GC) and Gas Chromatography/Mass Spectrometry (GC/MS). The investigated species were: Piper aduncum, P. amalago, P. arboreum, P. cernuum, P. hispidum, P. regnelii, P. submarginalum, P. vicosanum and Pothomorphe umbellata. Over 80% of the essential oils compounds were identified by the qualitative and quantitative analysis. The analysed species showed the predominance of sesquiterpenoids, except for P. hispidum, P. submarginalum and P. vicosanum in which the predominant compounds were monoterpenoids. For the 9 studied species, the major compounds found in the oils were beta-pinene (9/9) and spathulenol (9/9), followed by the E-caryophyllene (8/9), caryophyllene oxide (8/9), germacrene D (7/9), alpha-pinene (7/9) and limonene (6/9).

A terapia fotodinâmica (TFD) está baseada na administração e no acúmulo de fotossensibilizador, por exemplo, de tipo porfirina ou clorina, em tecidos doentes. As clorinas apresentam propriedades fotofísicas semelhantes àquelas das porfirinas, mas com intensificação e deslocamento das bandas Q, o que faz com que sejam bons candidatos para TFD. Neste trabalho relata-se a síntese da 5,10,15-tris(pentafluorofenil)-20-(4-piridil)porfirina, (2), e das clorinas isômeras 4, (5,10,20-tris(pentafluorofenil)-15-(4-piridil)-tetra-hidro-1H- N-metil-pirrolo[3,4-b]porfirina e 5, (5,10,15-tris(pentafluorofenil)-20-(4-piridil)-tetra-hidro-1H- N-metil-pirrolo[3,4-b]porfirina, obtidas a partir de 2, por reação de cicloadição 1,3-dipolar com um ileto azometínico, e respectivas caracterizações estruturais por UV-Vis, RMN e EM-FAB. Foram avaliadas as propriedades fotofísicas, fotoquímicas e fotodegradativas para a nova clorina 4, obtida com melhor rendimento que o seu isômero 5. O rendimento quântico de fotodegradação (fiFd, mol Einstein-1) foi de 0,047±0,014. Foram ainda realizados testes com ácido úrico para demonstrar a capacidade do fotossensibilizador na produção de ¹O2. Os resultados mostraram que a nova clorina 4 pode ser considerada como um bom fotossensibilizador para TFD.

Photodynamic therapy (PDT) is based on the accumulation of a photosensitizer, such as a porphyrin or a chlorin, in a malignant tissue after its administration. Chlorins exhibit photophysical properties similar to those of the porphyrin macrocycles, but with intensified and red-shifted Q bands, making chlorin-containing systems even better candidates for PDT. In this contribution, we report the synthesis of 5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)porphyrin, (2) and its transformation to the novel chlorin derivatives 4, (5,10,20-tris(pentafluorophenyl)-15-(4-pyridyl)-tetrahydro-1H- N-methyl-pyrrolo [3,4-b]porphyrin and 5, (5,10,15-tris(pentafluorophenyl)-20-(4-pyridyl)-tetrahydro-1H- N-methyl-pyrrolo[3,4-b]porphyrin) by 1,3-dipolar cycloaddition with an azomethine ylide. The new products have been characterized by UV-Vis, ¹H NMR and FAB-MS. The photophysics, photochemical and photobleaching properties of chlorin 4 have been evaluated. Its quantum yield of photobleaching (phiPb, mol Einstein-1) was 0.047±0.014. In order to demonstrate the production of ¹O2 when 4 is used as a photosensitizer, uric acid tests have been carried out. The results indicate that chlorin 4 can be considered a promising photosensitizer in PDT.

O estudo foi realizado com os objetivos de estabelecer a sensibilidade dos búfalos a Palicourea juruana e agregar novos dados sobre a toxidez dessa planta para bovinos. Embora os quadros clínico-patológicos tenham sido semelhantes, a comparação das doses letais para búfalos (entre 1 e 2 g/kg) e para bovinos (0,25 g/kg) estabelece o búfalo como pelo menos quatro vezes mais resistente. Em experimentos realizados 10 anos antes - com amostras de P. juruana coletadas na mesma fazenda no Pará, em julho de 1993, início da época de seca, portanto apenas 2 meses mais tarde do que os agora realizados em maio de 2003 - a dose letal para bovinos foi de 2 g/kg. Não encontramos explicação para a toxicidade extremamente elevada da planta verificada nesse estudo.

An experimental study was performed to establish the toxicity of Palicourea juruana for buffaloes and to add new data on the toxicity of this plant for cattle. The clinical and pathological pictures were similar, but a comparison of the lethal doses for buffaloes (1-2g/kg) and cattle (0.25g/kg) shows that the buffalo is at least 4 times more resistant. In experiments performed 10 years earlier with the fresh leaves - collected on the same farm in July, at the beginning of the dry season, only 2 months later than in this second experimental series - the lethal dose for cattle was 2 g/kg. No explanation was found for the extremely high toxicity of the plant observed in the present study.