Vascular endothelial growth factor-A enhances indoleamine 2,3-dioxygenase expression by dendritic cells and subsequently impacts lymphocyte proliferation

Dendritic cells (DCs) are antigen (Ag)-presenting cells that activate and stimulate effective immune responses by T cells, but can also act as negative regulators of these responses and thus play important roles in immune regulation. Pro-angiogenic vascular endothelial growth factor (VEGF) has been shown to cause defective DC differentiation and maturation. Previous studies have demonstrated that the addition of VEGF to DC cultures renders these cells weak stimulators of Ag-specific T cells due to the inhibitory effects mediated by VEGF receptor 1 (VEGFR1) and/or VEGFR2 signalling. As the enzyme indoleamine 2,3-dioxygenase (IDO) is recognised as an important negative regulator of immune responses, this study aimed to investigate whether VEGF affects the expression of IDO by DCs and whether VEGF-matured DCs acquire a suppressor phenotype. Our results are the first to demonstrate that VEGF increases the expression and activity of IDO in DCs, which has a suppressive effect on Ag-specific and mitogen-stimulated lymphocyte proliferation. These mechanisms have broad implications for the study of immunological responses and tolerance under conditions as diverse as cancer, graft rejection and autoimmunity.

Efficiency of five biosolids to supply nitrogen and phosphorus to ryegrass

Biosolids have been considered satisfactory to supply crops and plant nutrients. The ideal biosolids application rate should result in high crop yields and nutrient uptake, and leave low concentrations of nutrients in soils to avoid environmental problems. The objective of this study was to estimate the capacity of five biosolids to supply N and P to ryegrass (Lolium perenne) after a single application of either fertilizers or biosolids to a Spodosol and an Oxisol. Results showed that 6% - 36% of N and 3% - 7% of P applied as biosolids were recovered in plants grown on the Spodosol, while the range on the Oxisol was 26%-75% for N and 1.2%-3.7% for phosphorus. Biosolids' efficiency on supplying N and P to plants was similar to fertilizer on the Spodosol, but on the Oxisol it refrained to 65%-67% fertilizer's efficiency. After a single application of biosolids followed by six consecutive harvests, 25%-94% of the N and 93%-99% of the P were not used by plants and remain in the soils.

Indução de alterações morfológicas e anatômicas em folhas de abacaxizeiro 'Pérola' pelo ácido 2-(3-clorofenoxi) propiônico

Em estudo que visou controlar a floração natural do abacaxizeiro 'Pérola' com fitorreguladores, nas plantas pulverizadas com 50 e 100 mg L-1 (3 aplicações) do ácido 2-(3-clorofenoxi) propiônico (ACP), foram observadas alterações internas e externas nas folhas. O limbo foliar apresentou ligeiro estrangulamento na porção mediana das folhas 'E' e 'F' e próximo ao ponto de inserção no caule nas C' e 'D'. A cerca de 5-10 cm desse ponto surgiram estruturas similares a calos, que originaram raízes adventícias. A roseta central das plantas apresentou-se torcida, com as folhas mais curtas e largas. Cortes anatômicos permitiram observar, sob microscópio óptico (40X), que as raízes adventícias foram formadas a partir de meristemas nos feixes vasculares (xilema e floema), e que a estrutura anatômica foliar nos pontos de estrangulamento do limbo não foi alterada. Parênquima assimilador formou-se no córtex dessas raízes adventícias, indicando a realização de fotossíntese nesse tecido. A localização das raízes adventícias nas folhas correspondeu às áreas de provável acúmulo do produto pulverizado sobre as plantas. Os efeitos causados pelo ACP neste trabalho sugerem o seu uso em estudos relacionados à indução de enraizamento na propagação vegetativa (convencional e micropropagação) e na formação de calos "in vitro". E servem, também, para orientar novos estudos sobre a inibição da floração natural e seu uso prático, a fim de se evitar danos às plantas.

Produção da laranjeira-de-umbigo 'Monte Parnaso' com incisão anelar de ramos e uso de reguladores vegetais

A laranjeira-de-umbigo 'Monte Parnaso' (Citrus sinensis [L.] Osbeck) tem produtividade inferior a 10 kg de frutos/planta, em função de baixa fixação e/ou retenção de frutos. Com o propósito de solucionar esse problema, no ano agrícola de 2001-2002, plantas com 11 anos de idade, enxertadas sobre Poncirus trifoliata (L.) Raf., em Butiá, Rio Grande do Sul, foram submetidas aos seguintes tratamentos: 1) Testemunha: sem anelagem e sem reguladores vegetais; 2) Incisão anelar da casca dos ramos principais, 10 dias após a queda das pétalas (02-10-2001); 3) Incisão anelar da casca dos ramos no final da queda natural de frutos (08-11-2001); 4) Pulverização com 5 mg.L-1 de ácido giberélico (AG3), 10 dias após a queda das pétalas (02-10-2001); 5) Pulverização com 15 mg.L-1 de ácido 2,4 diclorofenoxiacético (2,4-D), no final da queda natural dos frutos (08-11-2001); 6) Pulverização com 50 mg.L-1 de ácido diclorofenoxipropiônico (2,4-DP), no final da queda natural dos frutos (08-11-2001); 7) Pulverização com 10 mg.L-1 de AG3 + 15 mg.L-1 de 2,4-D, em maio (14-05-2001 e 11-05-2002); 8) Tratamentos 2 + 3, e 9) Tratamentos 2 + 3 + 7. O delineamento experimental adotado foi em blocos ao acaso, com 5 repetições, usando 3 plantas úteis por parcela. A pulverização com 5 mg.L-1 de AG3, 10 dias após a queda das pétalas, aumenta a produção, mas diminui a massa média dos frutos em relação a outros tratamentos que aumentam a produção, e a pulverização no final da queda natural com 15 mg.L-1 de 2,4-D diminui o teor de suco dos frutos. Para aumentar a produção de frutos, basta adotar-se um dos seguintes procedimentos: em novembro, após a queda natural dos frutos, fazer a incisão anelar da casca dos ramos, ou pulverizar as plantas com 15 mg.L-1 de 2,4-D, ou pulverizar as plantas com 50 mg.L-1 de 2,4-DP; ou em maio, pulverizar as plantas com 10 mg.L-1 de AG3 + 15 mg.L-1 de 2,4-D.

A técnica da reflectância difusa aplicada ao estudo da fluorescência de 2,3-naftalimidas n-substituídas com grupos alquila incluídas em b-ciclodextrina e adsorvidas em celulose microcristalina

The solution fluorescence of N-alkyl-2,3-naphthalimides (1-4) in polar protic and aprotic solvents was compared to the emission from solid samples resulting from the imide complexation with b-cyclodextrin or adsorption on the surface of microcrystalline cellulose. Solid samples of the inclusion complex 2,3-naphthalimides/b-cyclodextrin show maximum for fluorescence emission significantly different to the observed in methanolic solution. Beside this, a clear effect on the alkyl chain length could be observed for these samples which is probably due to differences in probe location inside the cyclodextrin cavity. The constancy for fluorescence quantum yield and fluorescence lifetime for the imides 1 - 4 adsorbed on microcrystalline cellulose suggests that, independently of the polarity of the solvent used for sample preparation, the probe is preferentially located on the cellulose surface. An increase of fluorescence quantum yield and fluorescence lifetime for solid samples, when compared to the values obtained in solution for the different solvents employed in this study (acetonitrile, methanol and water), is fully in accordance with a decrease of the probe mobility due to inclusion in b-cyclodextrin or to adsorption on cellulose.

Espectro infravermelho e análise conformacional do composto 3-fenil-2-oxo-1,2,3-oxatiazolidina

The infrared (IR) spectra of the four distict conformers located on the multidimensional potential energy surface (PES) for the 3-phenyl-1,2,3-oxathiazolidine 2-oxide compound have been calculated using the semiempirical quantum-mechanical method PM3. The band spectra are reported and compared directly with the experimental spectrum. The IR intensities are shown to be much more sensitive to conformational changes than the vibrational frequencies and so, the theoretical analysis of the IR spectrum can be used as a tool for helping in the elucidation of the structure of heterocyclic compounds.

Heterociclos 1,2,3-triazólicos: histórico, métodos de preparação, aplicações e atividades farmacológicas

The 1,2,3-triazole, known since the end of 19th century, is a very widely used heterocyclic system present in many synthetic substances and commercial pharmaceutical compounds. In fact, 1,2,3-triazoles show several applications in many areas especially as medicines against many diseases like cancer, AIDS, Parkinson and Alzheimer. Nowadays there is a large variety of known methods to obtain these heterocyclic compounds comprising mainly three synthetic routes. Nevertheless, there is no article that gives an objective overview of the synthetic methods for obtaining these kinds of azoheterocycles. This paper presents a brief history of this class of compounds, and a synthetic discussion concerning the main synthetic methods for its preparation, such as cyclization through hydrazones, concerted cycloadditon [2+3] and pseudopericyclic cyclization - and some others of restricted application, but also important. Finally, this paper also provides a brief overview on pharmacological applications of some 1,2,3-triazoles.

A reação "click" na síntese de 1,2,3-triazóis: aspectos químicos e aplicações

The Copper-catalyzed azide-alkyne cycloaddition (CuAAC), often referred to as "click" reaction, has become a very popular reaction in the last years. It affords exclusively 1,4-disubstituted 1,2,3-triazoles and has been widely used to connect readily accessible building blocks containing various functional groups. The great success of this reaction is based on the fact that it is general, virtually quantitative and very robuste. The scope of this copper-catalyzed synthesis is extraordinary and the reaction has found numerous applications in many research fields, including biological chemistry and materials science. In this review, the main chemical aspects and applications of the "click" reaction in the synthesis of 1,2,3-triazoles are presented.

Anti-trypanosomal activity of 1,2,3,4,6-penta-O-galloyl-β -D-glucose isolated from Plectranthus barbatus Andrews (Lamiaceae)

MeOH extract from the leaves of Plectranthus barbatus Andrews (Lamiaceae), showed in vitro anti-trypanosomal activity. The bioassay-guided fractionation resulted in the isolation of a gallic acid derivative, identified as 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG), after thorough NMR and MS spectral analysis. Finally, this compound was tested against trypomastigote forms of T. cruzi and displayed an EC50 value of 67 µM, at least 6.6-fold more effective than the standard drug benznidazole. This is the first occurrence of PGG in the Plectranthus genus and the first anti-parasitic activity described for PGG in the literature.

SYNTHESIS AND BIOLOGICAL EVALUATION OF SPIRO[INDOLINE-3,4’-PYRANO[2,3-C:6,5-C’]DIPYRAZOL]- 2-ONES IN THE PRESENCE OF SBA-Pr-SO3H AS A NANOCATALYST

Sulfonic acid functionalized SBA-15 nanoporous material (SBA-Pr-SO3H) with a large pore size of 6 nm, a high surface area, high selectivity, and excellent chemical and thermal stability was applied as an efficient heterogeneous nanoporous acid catalyst in the reaction of isatin with pyrazolones under mild reaction conditions. A novel class of symmetrical spiro[indoline-3,4'-pyrano[2,3-c:6,5-c']dipyrazol]-2-one derivatives was successfully obtained in high yields. Comparison of these results with those reported in the literature shows that the current method is efficient, and results in better reaction times and yields of the desired products. Other advantages of this new method are its operational simplicity, easy work-up procedure, and the use of SBA-Pr-SO3H as a reusable and environmentally benign nanoreactor, such that the reaction proceeds easily in its nanopores. We also tested the antimicrobial activity of the prepared compounds using the disc diffusion method, and some of the synthesized compounds exhibited the best results against B. subtilis and S. aureus.

Comparison of some properties of Cu(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates

The physico-chemical properties and thermal stability in air of Cu(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates were compared and the influence of the position of -OCH3 substituent on their thermal stability was investigated. The complexes are crystalline, hydrated salts with blue colour. The carboxylate ion is a bidentate chelating or bridging group. The thermal stability of analysed Cu(II) dimethoxybenzoates was studied in the temperature range of 293-1173 K. The positions of methoxy- groups in benzene ring influence the thermal properties of studied complexes. Their different thermal properties are markedly connected with the various influence of inductive, mesomeric and steric effects of -OCH3 substituent on the electron density in benzene ring. The magnetic susceptibilities of the complexes were measured over the range of 76-300 K and the magnetic moments were calculated. The results show that they form dimers.

Magnetic, thermal and spectral properties of Ni(II) 2,3- , 3,5- and 2,6-dimethoxybenzoates

Complexes of Ni(II) 2,3-, 3,5- and 2,6-dimethoxybenzoates have been synthesized, their physico-chemical properties have been compared and the influence of the position of -OCH3 substituent on their properties investigated. The analysed compounds are crystalline, hydrated salts with green colour. The carboxylate ions show a bidentate chelating or bridging coordination modes. The thermal stabilities of Ni(II) dimethoxybenzoates were investigated in air in the range of 293-1173 K. The complexes decompose in three steps, yelding the NiO as the final product of decomposition. Their solubilities in water at 293 K are in the order of 10-2-10-4 mol×dm-3. The magnetic susceptibilities for the analysed dimethoxybenzoates of Ni(II) were measured over the range of 76-303 K and the magnetic moments were calculated. The results reveal that the complexes are the high-spin ones and the ligands form the weak electrostatic field in the octahedral coordination sphere of the central Ni(II) ion. The various position -OCH3 groups in benzene ring cause the different steric, mesomeric and inductive effects on the electron density in benzene ring.

Comparison of some properties of 2,3 - and 3,4 - dimethoxybenzoates of Cu(II), Co(II) and Nd(III)

The physicochemical properties of 2,4-, and 3,4- dimethoxybenzoates of Cu(II), Co(II) and Nd(III) were studied and compared to observe the -OCH3 substituent positions in benzene ring on the character of complexes. The analysed compounds are crystalline hydrated or anhydrous salts with colours depending on the kind of central ions: blue for Cu(II), pink for Co(II) and violet for Nd(III) complexes. The carboxylate groups bind as monodentate, bidentate bridging or chelating and even tridentate ligands. Their thermal stabilities were studied in air at 293-1173K. When heated the hydrated complexes release the water molecules and form anhydrous compounds which are then decomposed to the oxides of respective metals. Their magnetic moment values were determined in the range of 76-303K. The results reveal the compounds of Nd(III) and Co(II) to be the high-spin and that of Cu(II) forms dimer. The various positions of -OCH3 groups in benzene ring influence some of physicochemical properties of analysed compounds.

Influência do estrógeno e do interferon γ sobre a expressão da indoleamina-2,3-dioxigenase em cultura de células de placenta e embriões de ratas Wistar

Resumo: A indoleamina 2,3-dioxigenase (IDO) é uma enzima responsável por catabolizar o aminoácido triptofano. Sua presença no ambiente uterino placentário está relacionada à tolerância imunológica ao semi-aloenxerto, pois impede a proliferação de células imunológicas maternas, seja pela falta do aminoácido, ou pela ação de alguns catabólitos oriundos da quebra do triptofano, como o ácido quinolínico, que é tóxico principalmente para os linfócitos T. Pouco se conhece sob a influência de substâncias (hormônios e citocinas) presentes na interface materno fetal e a expressão dessa enzima. Por esta razão, formulou-se a hipótese de que hormônios e interleucinas presentes na região uteroplacentária poderiam exercer algum efeito na expressão da IDO. Células oriundas da interface materno fetal de ratas Wistar foram mantidas em cultivo, onde receberam suplementação com estradiol e interferon-γ. A expressão da enzima foi avaliada pela técnica de citometria de fluxo nos períodos de 4, 24 e 48 horas e confirmação da presença proteica por imuno-histoquímica. Os resultados mostraram um aumento na expressão de IDO após a adição de estrógeno (9,03±0,81/11,25±0,25) e interferon-γ (9,03±0,81/20,43±0,60). O efeito do interferon-γ já era esperado como relatado na literatura, contudo, a elevação da expressão da IDO pela adição do estrógeno constitui nova informação sobre possíveis mecanismos envolvidos na ativação da enzima. O melhor esclarecimento desses achados poderia contribuir para uma melhor compreensão da participação dessa enzima na tolerância materno-fetal e para uma futura modulação terapêutica da mesma.

Expressão da enzima indoleamina-2,3-dioxigenase em truta arco-íris (Oncorhynchus mykiss)

Resumo: A indoleamina 2,3-dioxigenase (IDO) é uma enzima que cataboliza o aminoácido triptofano, levando à inibição da proliferação de linfócitos T, seja pela exaustão desse aminoácido no ambiente, ou pela indução via catabólitos induzindo-os a apoptose. Em mamíferos, esta enzima atua em diversas condições do organismo como a gestação, infecções, inflamações crônicas, transplantes e tumores, atuando na regulação imunológica. Estudos recentes identificaram a presença de moléculas homólogas a IDO em espécies filogeneticamente inferiores, cuja função parece estar restrita ao metabolismo do triptofano como fonte de energia. Este estudo teve por objetivo averiguar a expressão da IDO em células sanguíneas e órgãos hematopoiéticos de truta arco-íris pela imuno-histoquímica, buscando evidências de que a mesma poderia, nesta espécie, estar relacionada ao sistema imune. A expressão de IDO foi observada nos órgãos hematopoiéticos estudados incluindo o rim cefálico que apresentou marcação em células interrenais e leucócitos; baço, na qual a marcação restringiu à alguns leucócitos; no fígado a marcação ficou limitada à apenas algumas células dentro dos vasos sanguíneos e nas extensões sanguíneas pode-se visualizar a marcação de alguns leucócitos como os monócitos, linfócitos e neutrófilos. A predominância da marcação da IDO nesses tecidos pode constituir uma evidência de que a IDO identificada na O. mykiss esteja relacionada ao sistema imunológico nessa espécie.