Polarizabilidades e primeira hiperpolarizabilidades elétricas dipolares de ésteres E-4-amino-trans-1,3-butadienil-(1',2'-di-hidroxibenzeno) de boro, alumínio e gálio

Static electric dipole polarizabilities and first hyperpolarizabilites have been calculated for the title molecules and their 3' and 4'-nitro derivatives at ab-initio Hartree- Fock/6-31G(d, p) level. The influence of the pivotal p vacant 3A elements (B, Al or Ga) substitution on the electrical properties of these molecules is detailed. The axial vector components of the first hyperpolarizabilities β(0) of the push-pull 4'-nitro derivatives, -18.2×10-32 esu (B), -21.1×10-32 esu (Al) and -20.8×10-32 esu (Ga) are calculated to be as much as fourfold larger then that calculated for the p-nitroaniline, a reference organic molecule for comparison for this type of molecular property.

Dft theoretical study of energetic nitrogen-rich C4N6H8-n(NO2)n derivatives

Density functional theory (DFT) calculations at the B3LYP/6-31G** theoretical level were performed for a series of guanidine-fused bicyclic skeleton derivatives C4N6H8-n(NO2)n (n = 1 - 6). The heats of formation (HOFs) were calculated by isodesmic reactions, and the detonation properties were evaluated using the Kamlet - Jacobs equations. The bond dissociation energies were also analyzed to investigate the thermal stability and sensitivity of the compounds. The results show that all of the derivatives have high positive HOFs, compound G has the highest theoretical density, and compound F1 has the highest detonation velocity and detonation pressure. Considering both the detonation properties and thermal stabilities, compounds D1 and D4 (3 nitro substituents), E1 - E6 (4 nitro substituents), and G (6 nitro substituents) can be regarded as potential candidates for high-energy density materials.

Ultrastructural alterations of intracellular stages and effects on blood forms of Trypanosoma cruzi induced in vivo by 2-amino-5-(1-methyil-5-nitro-2-imidazolyl)-1,3,4 - Thiadiazole

An electron microscopy study shows that the administration of a single dose (500 mg/kg, p.o.) of 2-amino-5-(1-methyl-5-nitro-2-imidazolyl)-1, 3, 4-thiadiazole induces in mice infected with Trypanosoma cruzi results in degenerative lesions of the intracellular stages. Ultrastructural alterations are detected as early as 6 hours after the drug administration and destruction of the parasites occurs within 18 - 36 hours. Trypomastigotes are cleared from the bloodstream 4 to 6 hours after treatment. The combined effect on both developmental stages is apparently responsible for the in vivo ejfects of this drug which is the most active drug ever tested in our laboratory in experimental Chagas' disease.

Reações de 1,2-dicloro-4,5-dinitrobenzeno com aminas: monossubstituição de nitro e dissubstituição de cloro e nitro

1,2-dichloro-4,5-dinitrobenzene (DCDNB) reacts with primary and secondary amines, in acetonitrile, at room temperature, to give a monosubstituted nitro product with a yield of 85 to 95%. The chloro-nitro-disubstituted product is formed with excess amine under reflux. Piperidine, pyrroline, dimethylamine and methylamine were the most reactive reagents in both mono- and disubstitution.

In Vitro and in Vivo Anti-Trypanosoma cruzi Activity of a Novel Nitro-derivative

Nitroarylidenemalononitriles and their cyanoacetamide derivatives with remarkable anti-epimastigote properties, were synthesized attempting to obtain new 3,5-diamino-4-(5'-nitroarylidene)-4H-thiadiazine 1,1-dioxide derivatives, which in previous reports had shown anti-Trypanosoma cruzi activity. Tests to evaluate the cytotoxicity of compounds were performed on J774 macrophages. 5-nitro-2-thienyl-malononitrile (5NO2TM), was the only product which maintained a high anti-epimastigote activity at concentrations in which it was no longer cytotoxic, thus it was assayed against intracellular amastigotes. Its anti-amastigote activity was similar to that of nifurtimox. Afterwards in vivo toxicity and anti-chagasic activity were determined. A reduction in parasitemia was observed.

Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide.

Nitro derivatives and other constituents of Aristolochia melastoma

A phytochemical study of Aristolochia melastoma Manso has led to the isolation and identification of 20 known compounds, including aristolochic acids, sodium aristolochates, lignan, flavonoids, and nitro phenylethyl derivatives. Their structures were established by spectroscopic analysis. The presence of thalictricoside and secoisolariciresinol dimethyl ether diacetate is reported for the first time in the Aristolochiaceae family. In addition, the presence of nitro compounds in this species is significant.

Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance

A new series of 3-chloro-1-{[2-(6-nitro-1H-indazol-1-yl)ethyl]amino}-4-(substituted phenyl)-2-azetidinones (4a-j) was synthesized in four steps from 6-nitro-1H-indazole and characterized by IR, ¹H NMR, 13C NMR, FAB-mass spectrometry and chemical methods. Compounds 4(a-j) were screened in vitro for their antibacterial, antifungal and antitubercular activities against some selected microorganism and for their antiinflammatory activity (in vivo) against albino rats (either sex). All above activities of compounds 4(a-j) showed acceptable results.

4-Aminopyridine inhibits the neuromuscular effects of nitric oxide and 8-Br-cGMP

The effects induced by nitric oxide (NO) in different tissues depend on direct and/or indirect interactions with K+ channels. The indirect interaction of NO is produced by activation of guanylyl cyclase which increases the intracellular cGMP. Since NO, cGMP and 4-aminopyridine alone induce tetanic fade and increase amplitude of muscular contractions in isolated rat neuromuscular preparations, the present study was undertaken to determine whether or not the neuromuscular effects of NO and 8-Br-cGMP can be modified by 4-aminopyridine. Using the phrenic nerve and diaphragm muscle isolated from male Wistar rats (200-250 g), we observed that L-arginine (4.7 mM) and 8-Br-cGMP (18 µM), in contrast to D-arginine, induced an increase in the amplitude of muscle contraction (10.5 ± 0.7%, N = 10 and 8.0 ± 0.7%, N = 10) and tetanic fade (15 ± 2.0%, N = 8 and 11.6 ± 1.7%, N = 8) at 0.2 and 50 Hz, respectively. N G-nitro-L-arginine (4 mM, N = 8 and 8 mM, N = 8) antagonized the effects of L-arginine. 4-Aminopyridine (1 and 10 µM) caused a dose-dependent increase in the amplitude of muscle contraction (15 ± 1.8%, N = 9 and 40 ± 3.1%, N = 10) and tetanic fade (17.7 ± 3.3%, N = 8 and 37.4 ± 1.3%, N = 8). 4-Aminopyridine (1 µM, N = 8) did not cause any change in muscle contraction amplitude or tetanic fade of preparations previously paralyzed with d-tubocurarine or stimulated directly. The effects induced by 4-aminopyridine alone were similar to those observed when the drug was administered in combination with L-arginine or 8-Br-cGMP. The data suggest that the blockage of K+ channels produced by 4-aminopyridine inhibits the neuromuscular effects induced by NO and 8-Br-cGMP. Therefore, the presynaptic effects induced by NO seem to depend on indirect interactions with K+ channels.

A execução da política externa brasileira: um balanço dos últimos 4 anos

Artigo de natureza institucional sobre execução da política exterior no primeiro Governo Fernando Henrique Cardoso. Essa política externa, cujos princípios de atuação são claramente definidos, foi marcada por um permanente esforço de intensificar o diálogo com outros setores do Governo e entidades civis (iniciativa privada, organizações sociais e a população em geral) e de aumentar a transparência do processo de decisão. O Itamaraty buscou modernizar-se para fazer frente aos desafios da sociedade globalizada e democratizada, cujo interesse por temas de política externa é crescente. Tais transformações se guiaram pela convicção de que a instituição precisa aperfeiçoar os serviços que presta à sociedade, por meio de ações que favoreçam mais diretamente os cidadãos brasileiros tanto no Brasil quanto no exterior.

Validade da aferição da acuidade visual realizada pelo professor em escolares de 1ª à 4ª série de primeiro grau de uma escola pública do município de São Paulo, Brasil

Trata-se de avaliação da medida da acuidade visual pelo professor, comparativamente àquela efetuada pelo médico-oftalmologista, utilizando-se ambos da tabela optométrica de Snellen. Éste estudo foi realizado em decorrência do Plano de Oftalmologia Sanitária Escolar (POSE), em desenvolvimento no Estado de São Paulo, que atinge escolares de 1ª série, classe especial e pré-primário das escolas estaduais de 1º grau, onde a atuação dos professores constitui fator básico da programação, principalmente no seu aspecto educativo e na verificação da acuidade visual. Foram testados 1.352 escolares de 1ª a 4ª série de 1º grau de um estabelecimento de ensino do município de São Paulo (SP) em 1975. Encontrou-se uma concordância de resultados em 80,86% dos casos. Com a diferença de 2 linhas entre os resultados do professor e do médico, constataram-se 122 casos (9,02%) e, com a diferença de 3 linhas, 54 casos (3,99%). À medida em que se consideravam diferenças maiores, decrescia progressivamente o número de casos discordantes encontrados. Observou-se que, à medida em que aumentava a desigualdade de aferição entre o professor e o oftalmologista, isto se verificava em ambos os olhos, o que evidencia uma dificuldade de interpretação daquelas crianças para responder o teste. Considerou-se altamente válida a aplicação do teste de acuidade visual pelo professor devidamente treinado, com a finalidade de triagem a nível de escola, como um dos aspectos para identificar alunos necessitados de exame médico-oftalmológico.

Ecological aspects of American cutaneous leishmaniasis: 4. Observations on the endophilic behavior of the sandfly and the vectorial role of Psychodopygus intermedius in the Ribeira Valley region of the S.Paulo State, Brazil

The invasive tendency of Psychodopygus intermedius in the home environment, observed initially by Forattini et al. (1976), has now been confirmed by the demonstration of its high endophilic ability and by the use of human residences for shelter. Populations such as Lutzomyia migonei and Pintomyia fischeri were also present in that environment, though their low densities registered during this investigation could be an indication of their poor ability to overcome the barriers raised by the artificial environment. An objective epidemiological analysis based on the variables here given showed that human infection takes place in the extraforest environment, and the principal vectorial function falls, without doubt, on P. intermedius.

Levantamento planorbídico do Estado de São Paulo (Brasil): 4ª Região Administrativa

A fim de conhecer a distribuição dos hospedeiros intermediários de S. mansoni no Estado de São Paulo (Brasil), a Superintendência de Controle de Endemias (SUCEN) procedeu a amplo inquérito malacológico em todos os municípios paulistas que teve a duração de 4 anos. As pesquisas realizadas na 4ª Região Administrativa que tem sede em Sorocaba e que constituem o objeto do presente relato, mostraram que Biomphalaria tenagophila (d'Orbigny, 1835) ocorre em 26 dos 59 municípios nela compreendidos. Biomphalaria glabrata (Say, 1818) é encontrada em 9 municípios e Biomphalaria straminea (Dunker, 1848), em 2. Vários casos de esquistossomose em migrantes já foram observados na área estudada. B. tenagophila parece estar implicada na cadeia natural de transmissão de S. mansoni em Itu e em São Roque, municípios em que foram descobertos os dois únicos casos da doença, até agora considerados como autóctones em toda a região.