Electroluminescent devices based on rare-earth tetrakis beta-diketonate complexes

In this paper the synthesis, photo luminescence and electroluminescence investigation of the novel tetrakis beta-diketonate of rare-earth complexes such as M[Eu(dbM)(4)] and M[Tb(acac)(4)] with a variety of cationic ligands, M=Li(+), Na(+) and K(+) have been investigated. The emission spectra of the Eu(3+) and Tb(3+) complexes displayed characteristic narrow bands arising from intraconfigurational transitions of trivalent rare-earth ions and exhibited red color emission for the Eu(3+) ion ((5)D(0) -> F(J), J=0-6) and green for the Tb(3+) ion ((5)D(4) -> (7)F(J), J = 6-0). The lack of the broaden emission bands arising from the ligands suggests the efficient intramolecular energy transfer from the dbm and acac ligands to Eu(3+) and Tb(3+) ions, respectively. In accordance to the expected, the values of PL quantum efficiency (eta) of the emitting (5)D(0) state of the tetrakis(beta-diketonate) complexes of Eu(3+) were higher compared with those tris-complexes. Therefore, organic electroluminescent (EL) devices were fabricated with the structure as follows: indium tin oxide (ITO)/hole transport layer (HTL) NPB or MTCD/emitter layer M[RE(beta-diketonate)(4)] complexes)/Aluminum (Al). All the films were deposited by thermal evaporation carried out in a high vacuum environment system. The OLED light emission was independent of driving voltage, indicating that the combination of charge carriers generates excitons within the M[RE(beta-diketonate)(4)] layers, and the energy is efficiently transferred to RE(3+) ion. As a best result, a pure red and green electroluminescent emission was observed from the Eu(3+) and Tb(3+) devices, confirmed by (X,Y) color coordinates. (C) 2008 Elsevier B.V. All rights reserved.

Synthesis and application of chiral beta-amino disulfides as ligands for the enantioselective addition of diethylzinc to aldehydes

A new class of chiral beta-amino disulfides was synthesized from readily available and inexpensive starting materials by a straightforward method and their abilities as ligands were examined in the enantioselective addition of diethylzinc to aldehydes. Enantiomeric excesses of up to 99% have been obtained using 0.5 mol % of the chiral catalysts.

Preparation of alpha,beta-Unsaturated Diazoketones Employing a Horner-Wadsworth-Emmons Reagent

A new method for the preparation of alpha,beta-unsaturated diazoketones from aldehydes and a Horner-Wadsworth- Emmons reagent is reported. The method was applied to the short synthesis of two substituted pyrrolidines.

Efeito do exercício físico sobre a liberação de interleucina-1[beta], interleucina-6 e fator de necrose tumoral-[alfa] em homens portadores de doença pulmonar obstrutiva crônica

A atividade física intensa pode induzir resposta inflamatória subclínica e aumento nos níveis plasmáticos de citocinas pró-inflamatórias. O objetivo deste estudo foi avaliar a relação entre a liberação de citocinas (IL-1β, IL-6, e TNF-α), o exercício físico agudo e o exercício regular em pacientes com doença pulmonar obstrutiva crônica (DPOC). Foram estudados 18 pacientes do sexo masculino com DPOC moderada a muito grave, divididos em dois grupos: 11 pacientes foram incluídos em programa de reabilitação pulmonar (RP) durante 8 semanas e 7 pacientes sem atividade física regular foram incluídos como grupo controle (C). Todos os pacientes realizaram espirometria, teste de exercício cardiopulmonar incremental máximo e teste de endurance em cicloergômetro com carga constante (60% da carga máxima do teste incremental) no início do projeto e após oito semanas. Foi coletado sangue venoso periférico para dosagem de citocinas, antes e 15 minutos após os testes de endurance (TE1 e TE2). IL-1β, IL-6, e TNF-α foram dosadas com kits ELISA específicos (Quantikine®, R&D Systems). Os pacientes submetidos à RP liberaram menos IL-1β que os controles após o treinamento (RP: TE1 0,96±0,66; TE2 -0,24±0,27 pg/ml; grupo C: TE1 -1,48±1,14; TE2 0,66±0,61 pg/ml; p=0,03). Não houve diferença significativa na liberação de IL-6 quando comparados os dois testes de endurance (RP: TE1 0,44±1,21; TE2 0,80±1,24 pg/ml; grupo C: TE1 0,88±0,85; TE2 0,78±0,95 pg/ml; p=0,68). Não foi observada diferença na liberação de IL-6 entre os dois grupos. Apenas cinco pacientes (quatro no grupo da RP) liberaram TNF-α e o exercício não modificou o seu padrão de liberação (RP: TE1 2,86±1,18; TE2 2,57±1,37pg/ml; grupo C: TE1 4,98; TE2 6,84 pg/ml; p=0,14). Não houve associação significativa entre intensidade de exercício e liberação de citocinas (IL-1β r=0,10; IL-6 r=-0,23). Houve maior liberação de IL-6 após o TE2 nos pacientes que apresentaram exacerbação da DPOC (exacerbados 9,59±1,32; estáveis 6,31±0,92 pg/ml; p=0,03) e não houve diferença nos níveis de IL-1β. Apenas pacientes com exacerbação da DPOC liberaram TNF-α (2,82±1,48 pg/ml). Concluiu-se que o exercício físico regular reduz a liberação de IL-1β e as exacerbações estimulam a liberação de IL-6 e TNF-α em pacientes com DPOC.

Prevention of bacterial translocation using β-(1-3)-D-glucan in small bowel ischemia and reperfusion in rats

To investigate the role of β-(1-3)-D-glucan on 99mTc labelled Escherichia coli translocation and cytokines secretion in rats submitted to small bowel ischemia/reperfusion injury. Methods: Five groups (n=10 each) of Wistar rats were subjected to control(C), sham(S), group IR subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R), and group I/R+glucan subjected to 45 min of bowel ischemia/60 min of reperfusion(I/R) and injected with 2mg/Kg intramuscular. Translocation of labelled bacteria to mesenteric lymph nodes, liver, spleen, lung and serum was determined using radioactivity/count and colony forming units/g(CFU/g). Serum TNFα, IL-1β, IL-6, IL-10 were measured by ELISA. Results: CFU/g and radioactivity/count were higher in I/R than in I/R+glucan rats. In C, S and S+glucan groups, bacteria and radioactivity/count were rarely detected. The I/R+glucan rats had enhancement of IL-10 and suppressed production of serum TNFα, IL-1β and, IL-6, compared to I/R untreated animals. Conclusion: The β-(1-3)-D-glucan modulated the production of pro-inflammatory and anti-inflammatory cytokines during bowel ischemia/reperfusion, and attenuated translocation of labelled bacteria

Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

Ropivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used in surgical procedures, which presents physico-chemical and therapeutic properties similar to those of bupivacaine (BPV), but associated to less systemic toxicity This study focuses on the development and pharmacological evaluation of a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-P-CD) inclusion complex. Phase-solubility diagrams allowed the determination of the association constant between RVC and HP-beta-CD (9.46 M-1) and showed an increase on RVC solubility upon complexation. Release kinetics revealed a decrease on RVC release rate and reduced hemolytic effects after complexation. (onset at 3.7 mM and 11.2 mM for RVC and RVCHP-beta-CD, respectively) were observed. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray) showed the formation and the morphology of the complex. Nuclear magnetic resonance (NMR) and job-plot experiments afforded data regarding inclusion complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed that RVCHP-beta-CD was able to reduce the latency without increasing the duration of motor blockade, but prolonging the duration and intensity of the sensory blockade (p < 0.001) induced by the LA in mice. These results identify the RVCHP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation. (c) 2007 Elsevier B.V All rights reserved.

Effects of 15d-PGJ(2)-loaded poly(D,L-lactide-co-glycolide) nanocapsules on inflammation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Aberrant expression of E-cadherin and beta-catenin proteins in placenta of bovine embryos derived from somatic cell nuclear transfer

Abnormal placental development is common in the bovine somatic cell nuclear transfer (SCNT)-derived fetus. In the present study, we characterised the expression of E-cadherin and beta-catenin, structural proteins of adherens junctions, in SCNT gestations as a model for impaired placentation. Cotyledonary tissues were separated from pregnant uteri of SCNT (n - 6) and control pregnancies (n - 8) obtained by artificial insemination. Samples were analysed by western blot, quantitative RT-PCR (qRT-PCR) and immunohistochemistry. Bovine trophectoderm cell lines derived from SCNT and control embryos were analysed to compare with the in utero condition. Although no differences in E-cadherin or beta-catenin mRNA abundance were observed in fetal tissues between the two groups, proteins encoded by these genes were markedly under-expressed in SCNT trophoblast cells. Immunohistochemistry revealed a different pattern of E-cadherin and total beta-catenin localisation in SCNT placentas compared with controls. No difference was observed in subcellular localisation of dephosphorylated active-beta-catenin protein in SCNT tissues compared with controls. However, qRT-PCR confirmed that the wingless (WNT)/beta-catenin signalling pathway target genes CCND1, CLDN1 and MSX1 were downregulated in SCNT placentas. No differences were detected between two groups of bovine trophectoderm cell lines. Our results suggest that impaired expression of E-cadherin and beta-catenin proteins, along with defective beta-catenin signalling during embryo attachment, specifically during placentation, is a molecular mechanism explaining insufficient placentation in the bovine SCNT-derived fetus.

Botryosphaeran, a new substrate for the production of beta-1,3-glucanases by Botryosphaeria rhodina and Trichoderma harzianum Rifai

Botryosphaeria rhodina and Trichoderma harzianum Rifai were grown on botryosphaeran (an exopolysaccharide (EPS) of the beta-1,3; 1,6-D-Glucan type produced by B. rhodina) as sole carbon source with the objective of producing beta-glucanases of the beta-type. Conditions for beta-1,3-glucanase production by T harzianum were examined by a statistical response surface method, and showed maximal enzyme production at 5 days growth in media containing 1.5 g/1 of EPS. Good agreement was obtained between the experimental values of beta-1, 3-glucanase activity and the corresponding values predicted by the mathernatical model. The crude beta-1,3-glucanase preparations were active towards a number of different beta-1,3-glucans and beta-glucosides. The mycelium of B. rhodina also proved to be a good substrate for beta-1,3-glucanase production by both fungal species. (c) 2005 Published by Elsevier Ltd.

Tetracaine stimulates insulin secretion through the mobilization of Ca2+ from thapsigargin- and IP3-insensitive Ca2+ reservoir in pancreatic beta-cells

The effect of tetracaine on Ca-45 efflux, cytoplasmic Ca2+ concentration [Ca2+](i), and insulin secretion in isolated pancreatic islets and beta-cells was studied. In the absence of external Ca2+, tetracaine (0.1-2.0 mM) increased the Ca-45 efflux from isolated islets in a dose-dependant manner. Tetracaine did not affect the increase in Ca-45 efflux caused by 50 mM K+ or by the association of carbachol (0.2 mM) and 50 mM K+. Tetracaine permanently increased the [Ca2+](i) in isolated beta-cells in Ca2+-free medium enriched with 2.8 mM glucose and 25 mu M D-600 (methoxiverapamil). This effect was also observed in the presence of 10 mM caffeine or 1 mu M thapsigargin. In the presence of 16.7 mM glucose, tetracaine transiently increased the insulin secretion from islets perfused in the absence and presence of external Ca2+. These data indicate that tetracaine mobilises Ca2+ from a thapsigargin-insensitive store and stimulates insulin secretion in the absence of extracellular Ca2+. The increase in Ca-45 efflux caused by high concentrations of K+ and by carbachol indicates that tetracaine did not interfere with a cation or inositol triphosphate sensitive Ca2+ pool in beta-cells.

Low protein diet confers resistance to the inhibitory effects of interleukin1 beta on insulin secretion in pancreatic islets

High protein content in the diet during childhood and adolescence has been associated to the onset insulin-dependent diabetes mellitus. We investigated the effect of interleukin-1 beta (IL-I beta) on insulin secretion, glucose metabolism, and nitrite formation by islets isolated from rats fed with normal protein (NP, 17%) or low protein (LP, 6%) after weaning. Pretreatment of islets with IL-1 beta for 1 h or 34 h inhibited the insulin secretion induced by glucose in both groups, but it was less marked in LP than in NP group. Islets from LP rats exhibited a decreased IL-1 beta -induced nitric oxide (NO) production, lower inhibition of D-[(UC)-C-14]-glucose oxidation to (CO2)-C-14, and less pronounced effect of IL-1 beta on alpha -ketoisocaproic acid-induced insulin secretion than NP islets. However, when the islets were stimulated by high concentrations of K+ the inhibitory effect of IL-1 beta on insulin secretion was not different between groups. In conclusion, protein restriction protects beta -cells of the deleterious effect of IL-1 beta, apparently, by decreasing NO production. The lower NO generation in islets from protein deprived rats may be due to increased free fatty acids oxidation and consequent alteration in Ca2+ homeostasis. (C) 2001 Elsevier B.V. All rights reserved.

Increased pancreatic islet mass is accompanied by activation of the insulin receptor substrate-2/serine-threonine kinase pathway and augmented cyclin D(2) protein levels in insulin-resistant rats

It is well known that glucocorticoids induce peripheral insulin resistance in rodents and humans. Here, we investigated the structural and ultrastructural modifications, as well as the proteins involved in beta-cell function and proliferation, in islets from insulin-resistant rats. Adult male Wistar rats were made insulin resistant by daily administration of dexamethasone (DEX; 1mg/kg, i.p.) for five consecutive days, whilst control (CTL) rats received saline alone. Structure analyses showed a marked hypertrophy of DEX islets with an increase of 1.7-fold in islet mass and of 1.6-fold in islet density compared with CTL islets (P < 0.05). Ultrastructural evaluation of islets revealed an increased amount of secreting organelles, such as endoplasmic reticulum and Golgi apparatus in DEX islets. Mitotic figures were observed in DEX islets at structural and ultrastructural levels. Beta-cell proliferation, evaluated at the immunohistochemical level using anti-PCNA (proliferating cell nuclear antigen), showed an increase in pancreatic beta-cell proliferation of 6.4-fold in DEX islets compared with CTL islets (P < 0.0001). Increases in insulin receptor substrate-2 (IRS-2), phosphorylated-serine-threonine kinase AKT (p-AKT), cyclin D(2) and a decrease in retinoblastoma protein (pRb) levels were observed in DEX islets compared with CTL islets (P < 0.05). Therefore, during the development of insulin resistance, the endocrine pancreas adapts itself increasing beta-cell mass and proliferation, resulting in an amelioration of the functions. The potential mechanisms that underlie these events involve the activation of the IRS-2/AKT pathway and activation of the cell cycle, mediated by cyclin D(2). These adaptations permit the maintenance of glycaemia at near-physiological ranges.

beta-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary beta-carotene (BC), on ventricular remodeling and survival after myocardial infarction (MI). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n = 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 100 g were administered one of the treatments until they weighed 200 to 250 g (similar to 5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation.

Granulocytic sarcoma of the small intestine with CBF beta/MYH11 fusion gene: report of an aleukaemic case and review of the literature

Granulocytic sarcomas (GS) are rare extramedullary tumours composed of immature myeloid cells. Inversion of chromosome 16 [inv(16)] is a cytogenetic marker for M4Eo subtype of acute myeloid leukaemia (AML). The possibility of an association between the development of granulocytic sarcoma of the small intestine (GSSI) and the M4Eo subtype of AML was suggested in nine previous case reports.Here we report an aleukaemic case of GSSI with inv(16) and its molecular equivalent, the CBFbeta/MYH11 fusion gene, detected by reverse transcriptase-polymerase chain reaction (RT-PCR), that after treatment with conventional AML chemotherapy followed by autologous bone marrow transplantation, achieved complete haematological and molecular remission on bone marrow examination. After chemotherapy, a thickened ileum wall positive for CBFbeta/MYH11 on tumour mass samples was still observed on computed tomography (CT) studies, raising the question of residual GS representing a reservoir of malignant cells. This case demonstrates the critical need of multidisciplinary diagnosis and follow-up of this entity combining immunopathologic, cytogenetic and molecular studies, reinforcing the potentiality of risk-adapted therapy strategies, as it is increasingly claimed for patients with overt AML. (C) 2003 Elsevier Ltd. All rights reserved.