Sensitive spectrophotometric determination of lamotrigine in bulk drug and pharmaceutical formulations using bromocresol green

Two new, simple, rapid and reproducible spectrophotometric methods have been developed for the determination of lamotrigine (LMT) both in pure form and in its tablets. The first method (method A) is based on the formation of a colored ion-pair complex (1:1 drug/dye) of LMT with bromocresol green (BCG) at pH 5.02±0.01 and extraction of the complex into dichloromethane followed by the measurement of the yellow ion-pair complex at 410 nm. In the second (method B), the drug-dye ion-pair complex was dissolved in ethanolic potassium hydroxide and the resulting base form of the dye was measured at 620 nm. Beer's law was obeyed in the concentration range of 1.5-15 µg mL-1 and 0.5-5.0 µg mL-1 for method A and method B, respectively, and the corresponding molar absorptivity values are 1.6932 x 10(4) and 3.748 x 10(4) L mol-1cm-1. The Sandell sensitivity values are 0.0151 and 0.0068 µg cm-2 for method A and method B, respectively. The stoichiometry of the ion-pair complex formed between the dug and dye (1:1) was determined by Job's continuous variations method and the stability constant of the complex was also calculated. The proposed methods were applied successfully for the determination of drug in commercial tablets.

Caracterização cultural, morfológica e patogênica de Lasiodiplodia theobromae associado a frutíferas tropicais

Lasiodiplodia theobromae é um fungo cosmopolita, polífago e oportunista, com reduzida especialização patogênica, capaz de infectar espécies de plantas em regiões tropicais e temperadas, causando os mais variados sintomas. Este estudo teve como objetivo caracterizar isolados de L. theobromae associados a frutíferas tropicais na região nordeste, considerando os aspectos cultural, morfológico e patogênico. Foram avaliados o crescimento micelial, coloração da colônia, dimensões dos conídios e patogenicidade dos isolados em mudas de cajazeira (Spondia mombin L.), cajueiro (Anacardium occidentale L.), gravioleira (Annona muricata L.) e umbuzeiro (Spondias tuberosa Arruda). Os dados de caracterização morfológica e cultural revelaram diversidade na população do patógeno. Alta variabilidade patogênica foi também detectada, embora não tenha sido possível observar especificidade patogênica em cajueiro. O umbuzeiro apresentou maior resistência relativa ao fungo. Os dados demonstraram também uma interação entre as características morfo-culturais e a patogenicidade dos isolados de L. theobromae.

Análise econômica baseada em funções de resposta da produtividade versus lâminas de água para o mamoeiro no Norte Fluminense

A potencialidade de um pólo de fruticultura irrigada no Norte Fluminense é enorme, dada a região apresentar muitas vantagens. Entretanto, a viabilidade de um sistema de produção dependerá do adequado manejo do mesmo, carecendo de análises econômicas dos insumos aplicados e dos resultados obtidos para estabelecer uma diretriz. Baseado nessas premissas, o objetivo deste trabalho foi avaliar o manejo da água a aplicar por meio de análises econômicas das funções de resposta (água x produção) e, ainda, considerando os diferentes mercados a atingir, nacional e internacional. Foi montado um experimento com diferentes lâminas de irrigação na cultura do mamão, com a cultivar "Improved Sunrise Solo 72/12", plantada em fileiras duplas, com espaçamento 3,6 x 2,0 x 2,0 m. Foi utilizado um sistema de irrigação por microaspersão com vazão e pressão de 9,7 x 10-3 L s-1 e 150 kPa, respectivamente. Os níveis de irrigação aplicados foram em função da evapotranspiração de referência (ET0), ou seja, 0; 40; 80; 120; 160; 200 e 240% da ETo. Os resultados encontrados, no período de 16 meses, permitiram estimar que as lâminas ótimas econômicas (precipitação + irrigação) foram de 2.818 e 2.832 mm, correspondendo a 45,4 e 35,5 t ha-1 de produtividade do mercado nacional e internacional, respectivamente.

Estimativa do custo de implantação da agricultura irrigada, utilizando o sistema de informação geográfica

A proposta deste trabalho foi utilizar o Sistema de Informações Geográficas (SIG) com o objetivo de indicar áreas agroeconomicamente mais aptas para a implantação da cultura do coqueiro irrigado. Foram utilizadas informações referentes ao assentamento rural Antonio Farias, localizado no município de Campos dos Goytacazes, região Norte do Estado do Rio de Janeiro. O software IDRISI 32 gerou informações que técnicos, extensionistas e produtores rurais podem utilizar no planejamento da agricultura em áreas irrigadas. Foram utilizados mapas digitais de solo e planialtimetria, além de mapas temáticos com informações de drenagem, estradas e limite dos lotes. A partir de operações de sobreposição dos temas solo, clima e relevo, foram criados novos mapas temáticos, que mostram os gastos parciais para implantar 1 ha irrigado da cultura do coqueiro-anão. O gasto de implantação foi composto pela soma dos desembolsos para a compra de calcário, fertilizantes, tubulação e moto-bomba. A partir dos mapas criados, foram observadas variações expressivas nos desembolsos para implantação de 1 ha de coqueiro irrigado entre os lotes do assentamento. Foi possível observar que a metodologia utilizada se mostrou eficaz na identificação das áreas mais aptas, sob o ponto de vista agroeconômico, para a implantação de culturas irrigadas, sendo facilmente aplicável para outras culturas e áreas de estudo.

Hematologic, serum biochemistry and urinary values for captive Crab-eating Fox (Cerdocyon thous) in São Paulo state, Brazil

The importance of studies with hematological, serum biochemistry and urinary values of Crab-eating Fox (Cerdocyon thous) is based on the need for health care and maintenance of those populations. This paper has the objective to investigate hematological, serum biochemistry and urinary physiological parameters of the Crab-eating fox, comparing gender and age differences. Blood samples were collected in 2003 from 52 animals of different Zoos in São Paulo state, Brazil; 7mL of blood was used to obtain a complete blood cell count (CBC) and the profile of the serum biochemistry. Moreover, 5mL of urine were collected for analysis. There was no difference in values for male and female animals, as for the CBC and serum biochemistry. Some hematological and serum biochemical parameters were influenced by age, showing significant differences. Urinalysis results were just demonstrated in a descriptive form. The studied values were, RBC 4.35±0.73 x 10(6) /µL, WBC 7.72±3.66 x 10³ /µL (predominance of segmented neutrophils), platelets 227.06±111.58 x 10³ /µL, urea 43.06±14.28mg/dL and creatinine 1.03±0.24mg/dL. Hematological, serum biochemistry and urinary values obtained in this study can be used as physiological values of the captive Crab-eating Fox. It is possible to conclude that wild species need their own reference values, differentiating animals in captivity from free-ranging animals.

Monitoramento do ciclo estral de cutias (Dasyprocta leporina Lichtenstein, 1823) através de citologia esfoliativa vaginal e ultrassonografia

O objetivo deste estudo foi monitorar o ciclo estral em cutias (Dasyprocta leporina) criadas em cativeiro no semiárido brasileiro. Durante 70 dias, cinco cutias foram diariamente submetidas a citologia esfoliativa vaginal, e o monitoramento ultrassonográfico ovariano foi realizado a cada três dias. Um total de 8 ciclos estrais foi completamente monitorado, com duração de 28,2±0,7 dias, variando de 24 a 31 dias. Pela citologia esfoliativa vaginal, houve uma predominância de células superficiais nas fases de proestro e estro (P<0,05), seguida da predominância de células intermediárias no metaestro (P<0,05) e de células parabasais no diestro (P<0,05). Por ultrassonografia, não houve diferenças na morfologia ovariana durante as diferentes fases do ciclo estral (P>0,05). Os folículos foram identificados durante as fases estrogênicas (proestro e estro), com diâmetro médio de 1±0,5mm. Em apenas 12,5% das fases luteais, corpos lúteos medindo 1,4±0,9mm foram identificados. Conclui-se que a associação da citologia vaginal e da ultrassonografia ovariana constitui uma alternativa viável para o monitoramento de ciclos estrais e identificação das fases estrogênicas em cutias da espécie Dasyprocta leporina

Nota científica: métodos para estimativa da area foliar de plantas daninhas: 2: Wissadula subpeltata (Kuntze) Fries

Com o objetivo de obter uma equação que, através de parâmetros lineares dimensionais das folhas, permitisse estimar a área foliar de Wissadula subpeltata (Kuntze) Fries, estudaram- se correlações entre a área foliar real e o comprimento da folha ao longo da nervura principal (C ), largura máxi ma da folha (L) , comprimento do espaço entre o ponto de inserção do pecíolo na folha até a primeira ramificação da nervura principal (CE), L + C, L x C e L x CE. Todas as equações, geométricas ou lineares simples, permitiram boas estimativas da área foliar . Do pont o de vista prático, sugere- se optar pela equação linear simples envolvendo o produto C x L, considerando o coeficiente linear igual a zero. Deste modo, a estimativa da área foliar de W. subpeltata pode ser feita pel a fórmula Y = 0, 85 49 (C x L), ou seja 85 ,49% do produto entre o comprimento da nervura principal e a largura máxima da folha.

Caracterização da área foliar de Merremia aegyptia

O conhecimento da área foliar de plantas daninhas pode auxiliar o estudo das relações de interferência entre elas e as culturas agrícolas. O objetivo desta pesquisa foi determinar uma equação matemática que estime a área foliar de Merremia aegyptia, a partir da relação entre as dimensões lineares dos limbos foliares. Folhas da espécie foram coletadas de diferentes locais na Universidade Estadual Paulista, Jaboticabal, Brasil, medindo-se o comprimento (C), a largura máxima (L) e a área foliar de três tipos de folíolos. Foram estimadas equações lineares (Y = a*X) para cada tipo de folíolo. A área foliar da espécie pode ser estimada pelo somatório das áreas dos limbos foliares de cada tipo de folíolo, por meio da equação AFest = 0,547470(X) + 1,145298(Y) + 1,244146(Z), em que X indica C*L do folíolo principal e Y e Z indicam C*L médios dos folíolos primário e secundário, respectivamente.

Long-term outcome of 25 children and adolescents with severe aplastic anemia treated with antithymocyte globulin

Severe aplastic anemia (SAA) is probably an immune-mediated disorder, and immunosuppressive therapy is recommended for patients with no available donor for bone marrow transplant. Between October 1984 and November 1987, 25 consecutive children and adolescents with SAA with no HLA-compatible marrow donor received equine antithymocyte globulin (ATG) (15 mg kg-1 day-1) for 10 days. The patients were evaluated 6 weeks, 6 months, and 12 months after starting ATG treatment. Thereafter, patients were evaluated yearly until July 1998. Median age was 10 years (range, 1.5-20 years), granulocyte counts on referral ranged from 0.032 to 1.4 x 10(9)/l (median 0.256 x 10(9)/l), and 12 patients had granulocyte counts &lt;0.2 x 10(9)/l. At a median follow-up of 9.6 years (range, 8.6-11.8 years), 10 patients (40%) remained alive with good marrow function. No morphologic evidence of hematological clonal disorders has been observed, although two patients probably have acquired clonal chromosomal abnormalities (trisomy 8 and del(6)q21, respectively). Responses to ATG were observed between 6 weeks and 6 months from the start of treatment in 60% of evaluable patients. The response rate was not different in patients whose granulocyte count at diagnosis was &lt;0.2 x 10(9)/l, or in those who were &lt;10 years of age. This study supports the view that, when compared with supportive measures, ATG is an effective treatment for children or adolescents with SAA. Although these results are inferior to those reported for marrow transplantation or more intensive immunosuppressive regimens, these patients who responded to ATG are long-term survivors with stable peripheral blood counts and a low rate of relapse.

Growth inhibitory effect and Chk1-dependent signaling involved in G2/M arrest on human gastric cancer cells induced by diallyl disulfide

Diallyl disulfide (DADS) inhibits growth and induces cell cycle G2/M arrest in human gastric cancer MGC803 cells. In this study, 15 mg/L DADS exerted similar effects on growth and cell cycle arrest in human gastric cancer BGC823 cells. Due to the importance of cell cycle redistribution in DADS-mediated anti-carcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. We hypothesized that DADS could mediate G2/M phase arrest through either Chk1 or Chk2 signal transduction pathways. We demonstrated that DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, and that DADS down-regulated Cdc25C and cyclin B1. The expression of mRNA and total protein for Chkl and Chk2 was unchanged. Chk1 is specifically phosphorylated by ATR (ATM-RAD3-related gene). Western blot analysis showed that phospho-ATR was activated by DADS. Taken together, these data suggest that cell cycle G2/M arrest, which was associated with accumulation of the phosphorylated forms of Chk1, but not of Chk2, was involved in the growth inhibition induced by DADS in the human gastric cancer cell line BGC823. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/Cdc25C/cyclin B1, and is independent of Chk2.

Dynamics of immunosuppression in hamsters with experimental visceral leishmaniasis

Immunosuppression has been reported to occur during active visceral leishmaniasis and some factors such as the cytokine profile may be involved in this process. In the mouse model of cutaneous leishmaniasis using Leishmania (Leishmania) major, the Th1 response is related to protection while the Th2 response is related to disease progression. However, in hamsters, which are considered to be an excellent model for the study of visceral leishmaniasis, this dichotomy is not observed. Using outbred 45- to 60-day-old (140 to 150 g) male hamsters infected intraperitoneally with 2 x 10(7) L. (L.) chagasi amastigotes, we evaluated the immune response of spleen cells and the production of cytokines. We used 3 to 7 hamsters per group evaluated. We detected a preserved response to concanavalin A measured by index of proliferation during all periods of infection studied, while a proliferative response to Leishmania antigen was detected only at 48 and 72 h post-infection. Messenger RNA from cytokines type 1 (IL-2, TNF-α, IFN-γ) and type 2 (IL-4, IL-10 and TGF-β) detected by reverse transcriptase polymerase chain reaction and produced by spleen cells showed no qualitative difference between control non-infected hamsters and infected hamsters during any period of infection evaluated. Cytokines were measured by the DNA band intensity on agarose gel using the Image Lab 1D L340 software with no differences observed. In conclusion, the present results showed an antigen-dependent immunosuppression in hamsters with active visceral leishmaniasis that was not related to the cytokine profile.

Association between the c.910A>G genetic variant of the XRCC1 gene and susceptibility to esophageal cancer in the Chinese Han population

Esophageal cancer (EC) is a common malignancy worldwide. The X-ray repair cross-complementing 1 gene (XRCC1) is one of the most important candidate genes for influencing susceptibility to EC. This study aimed to investigate the effect of XRCC1 genetic variants on susceptibility to EC. A total of 383 EC patients (males: 239, females: 144, mean age: 56.62) and 387 cancer-free controls (males: 251, females: 136, mean age: 58.23) were enrolled in this study. The c.910A>G genetic variant of theXRCC1 gene was determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing methods. The allele and genotype frequencies indicated statistical differences between EC patients and cancer-free controls. The c.910A>G genetic variant was statistically associated with increased susceptibility to EC [GGvs AA: odds ratio (OR)=1.79, 95% confidence interval (CI)=1.12-2.86, P=0.014; GG vs AG/AA: OR=1.76, 95%CI=1.13-2.75, P=0.013; G vs A: OR=1.25, 95%CI=1.01-1.55, P=0.041]. The allele G and genotype GG could contribute to the increased susceptibility to EC. Our findings suggest that the c.910A>G genetic variant is associated with susceptibility to EC in the Chinese Han population, and might be used as a molecular marker for detecting susceptibility to EC.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)-based scaffolds for tissue engineering

Development and selection of an ideal scaffold is of importance for tissue engineering. Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a biocompatible bioresorbable copolymer that belongs to the polyhydroxyalkanoate family. Because of its good biocompatibility, PHBHHx has been widely used as a cell scaffold for tissue engineering. This review focuses on the utilization of PHBHHx-based scaffolds in tissue engineering. Advances in the preparation, modification, and application of PHBHHx scaffolds are discussed.

Meta-analysis on the efficacy and tolerability of the augmentation of antidepressants with atypical antipsychotics in patients with major depressive disorder

We assessed the efficacy and tolerability of the augmentation of antidepressants (ATDs) with atypical antipsychotics (AAPs) to treat patients with major depressive disorder. A retrograde study to identify relevant patient data included databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Database of Abstracts of Reviews of Effects. Data from 17 trials, involving 3807 participants, were identified. The remission rate (RR) and overall response rate (ORR) of adjunctive treatment with AAPs were significantly higher than placebo treatment: RR=1.90 (95%CI=1.61-2.23, z=7.74, P<0.00001) and ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001). We found that the short-term (4 weeks) treatment [ORR=1.70 (95%CI=0.98-2.95, Z=1.89, P=0.06)] was significantly different from the long-term (6-12 weeks) treatment [ORR=1.68 (95%CI=1.45-1.94, z=7.07, P<0.00001)]. No significant difference in ORR was observed between groups with or without sedative drugs. The discontinuation rate due to adverse effects was higher for adjunctive treatment with AAPs: ORR=3.32 (95%CI=2.35-4.70, z=6.78, P<0.00001). These results demonstrate that the augmentation of ATDs with AAPs (olanzapine, quetiapine, aripiprazole, and risperidone) was more effective than a placebo in improving response and remission rates, although associated with a higher discontinuation rate due to adverse effects.

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.