Temperature-dependent benzoic acid elimination mechanisms in pyrolysis of (-)-cocaine

The thermal elimination of benzoic acid from (-)-cocaine is shown to be temperature-dependent. In the temperature range of 200-500 °C only a trans-elimination is observed leading to methylecgonidine. Above ca. 500 °C a second mechanism, the cis-elimination, comes up yielding a novel alkaloid methylisoecgonidine which has been characterized by means of mass spectrometry. At 600 °C the cis-elimination predominates. The trans-elimination is postulated a two-step process consisting of a 1,7- and a 1,5-hydrogen shift. The chemistry of cocaine base smoking is explained using the theory of chemical activation.

Influência da saponificação na determinação de carotenoides em maracujás do cerrado

This work describes the evaluation of the effect of saponification process in the carotenoid's content of three species of passion fruit. The results indicated the saponification of the extract was necessary to obtain cis-violaxanthin, trans-violaxanthin and β-cryptoxanthin hydrolyzed. These compounds were found in fruits of commercial P. edulis and yellow wild P. edulis. However, the extract saponification did not permitted to obtain free carotenes in fruits of wild purple P. edulis and P. setacea, and to trans-violaxanthin of P. cincinnata, therefore saponification was not indicated in the carotenoid analysis of these three accessions of passion fruit.

Extração de ácido trans-trans mucônico urinário com polímeros de impressão molecular e análise por cromatografia gasosa: espectrometria de massas

This paper describes selective molecularly imprinted solid-phase extraction of ttMA from urine samples followed by derivatization and analysis by gas chromatography/mass spectrometry (GC/MS). The analytical calibration curve ranged from 0.3 to 7.0 mg L-1 (r = 0.999) and the limit of quantitation (LOQ) was 0.3 mg L-1. The method was applied for the determination of ttMA in urine samples from smokers and concentrations detected ranged from < LOQ to 1.64 mg L-1. Thus, the proposed method proved adequate for the determination of urinary ttMA in the biomonitoring of occupational exposure to low levels of benzene.

Descriptores globales y locales de la reactividad para el diseño de nuevos fármacos anticancerosos basados en cis-platino(II)

Density functional theory was used to investigate the global and local reactivity of some cis-platinum(II) complexes including anticancer drugs, such as cisplatin and carboplatin. Calculated equilibrium geometries at mPW1PW/LANL2DZ* are in close agreement with their available X-ray data. We develop three new local reactivity descriptors: atomic descriptor of philicity, atomic descriptor group and atomic descriptor of philicity group for determining chemical reactivity and selectivity of the studied complexes. This contribution on chemical reactivity allow us to establish qualitative trends, which enable our descriptors for use in rational platinum based anticancer drug design.

CHEMICAL COMPOSITION VARIABILITY IN THE Uncaria tomentosa (cat’s claw) WILD POPULATION

Uncaria tomentosa (cat's claw) is a vine widely distributed throughout the South-American rainforest. Many studies investigating the chemical composition of cat's claw have focused on the pentacyclic (POA) and tetracyclic oxindole alkaloids (TOA), quinovic acid glycosides (QAG), and polyphenols (PPH). Nevertheless, it is still uncertain how environmental factors affect chemical groups. The aim of this work was to better understand the influence of environmental factors (geographic origin, altitude, and season) on cat's claw chemical composition. Stem bark, branches and leaf samples were extracted and analyzed by HPLC-PDA. The data obtained were explored by multivariate analysis (HCA and PCA). Higher amounts of oxindole alkaloids and PPH were found in leaves, followed by stem bark and branches. No clear relationship was verified among geographic origin or altitude and chemical composition, which remained unchanged regardless of season (dry or rainy). However, three oxindole alkaloid chemotypes were clearly recognized: chemotype I (POA with cis D/E ring junction); chemotype II (POA with trans D/E ring junction); and chemotype III (TOA). Thus, environmental factors appear to have only a minor influence on the chemical heterogeneity of the cat's claw wild population. Nevertheless, the occurrence of different chemotypes based on alkaloid profiles seems to be clear.

Avaliação por espestroscopia no infravermelho da microestrutura de poliuretano baseado em resina polibutadiênica hidroxilada

Este trabalho apresenta uma avaliação da microestrutura ou seja, dos teores dos isômeros 1,4-cis, 1,4-trans e 1,2-vinil do segmento flexível de um poliuretano (PU) preparado a partir de resina polibutadiênica hidroxilada (PBLH), por meio da análise no infravermelho empregando-se a técnica de pastilha com brometo de potássio.

Análise conformacional de compostos de Biginelli com atividade antineoplásica

Diidropirimidinonas são heterociclos com atividade antineoplásica conhecida. O monastrol e alguns análogos são exemplos. A análise conformacional representa uma etapa preliminar importante em estudos que visam correlacionar a estrutura do composto com sua atividade. Neste trabalho, descrevemos a análise conformacional do monastrol e diversos análogos por cálculo semi-empírico AM1 e ab initio HF/6-31G*. Quatro geometrias de equilíbrio foram encontradas (s-cis/ap, s-cis/sp, s-trans/ap e s-trans/sp), tendo como rotações internas importantes a do sistema carbonilado α,β-insaturado e a do grupo arila ligado ao heterociclo.

Esofagectomia trans-hiatal no tratamento do megaesôfago chagásico avançado

OBJETIVO: Avaliar os resultados da esofagectomia trans-hiatal no tratamento do megaesôfago chagásico avançado. MÉTODO: Foram estudados retrospectivamente 28 pacientes portadores de megaesôfago chagásico avançado (MCA), graus III e IV, segundo a classificação radiológica de Rezende (adotada pela Organização Mundial de Saúde), e que foram submetidos à esofagectomia subtotal trans-hiatal no Serviço de Clínica Cirúrgica do Hospital Universitário Prof. Alberto Antunes (HUPAA) da Universidade Federal de Alagoas, entre 1982 e 2000. Foram analisadas, as seguintes variáveis: A) Queixas clínicas pré-operatórias versus as pós-operatórias (disfagia, regurgitação, pirose, diarréia, dumping, plenitude pós-prandial, pneumonia e o estado ponderal). B) avaliação radiológica pós-operatória da boca anastomótica esofagogástrica cervical e do estômago transposto. C) avaliação endoscópica pós-operatória do coto esofágico e da boca anastomótica. RESULTADOS: O seguimento variou de 4 a 192 meses, média de 58,18 meses. Dezesseis pacientes eram do sexo feminino e 12 masculinos. Idade mínima de 16 e máxima de 67 anos, média de 36,5 anos. Não houve mortalidade nesta série. Houve resolução plena da disfagia na maioria dos pacientes (20/28 - 71,4%), um (3,6%) referiu disfagia leve que não necessitou tratamento e 7/28 (25%) necessitaram de uma ou mais sessões de dilatação. Nenhum necessitou de dilatação permanente. A pirose foi o sintoma mais importante no seguimento tardio (35,7%), seguida da regurgitação (25%), diarréia (14,3%), plenitude pós-prandial (10,7%) e dumping (3,6%). Houve ganho ponderal em 87,5% dos pacientes avaliados. A esofagite no coto esofágico foi o achado endoscópico mais significativo (46,4%). O esôfago de Barrett no coto remanescente foi encontrada em 10,7% dos casos. A maioria dos achados radiológicos foi normal, embora três doentes (10,7%) tenham apresentado estase gástrica. CONCLUSÃO: A esofagectomia trans-hiatal mostrou-se eficaz para o tratamento da disfagia no megaesôfago chagásico avançado, embora com morbidade elevada, porém com mortalidade nula.

Esofagectomia trans-hiatal versus transtorácica: experiência do Instituto Nacional do Câncer (INCA)

OBJETIVO: Analisar comparativamente a morbimortalidade e sobrevida após esofagectomia trans-hiatal (TH) ou transtorácica (TT). METODOS: Estudo retrospectivo não randomizado de 68 pacientes com neoplasia de esôfago operados no INCA entre 1997 e 2005, divididos em dois grupos: 1 - TH (33 pacientes); e 2 - TT (35 pacientes). RESULTADOS: A idade média foi 40,7 anos (25 - 74 anos), sendo 73,5% homens. Tumores do 1/3 médio predominaram no Grupo 2 (48,6% versus 21,2%, p = 0,02). A média de linfonodos dissecados foi maior no Grupo 2 (21,6 versus 17,8 linfonodos, p = 0,04), porém sem diferença no número de linfonodos metastáticos (4,1 versus 3,9 linfonodos, p = 0,85). O tempo cirúrgico médio foi maior no Grupo 2 (410 versus 270 minutos, p = 0,001). O tempo médio de internação também foi maior no Grupo 2 (19 versus 14 dias, p = 0,001). A morbidade operatória foi 50%, sem diferença significativa (42,4% versus 57,1%, p = 0,23). Fístula esofágica ocorreu em 13,2%, sem diferença significativa (9,1% versus 17,1%, p = 0,23). A mortalidade foi 5,8% (04 pacientes), sem diferença significativa (1,4% versus 4,4%, p = 0,83). CONCLUSÃO: Neste estudo, a morbimortalidade não apresentou diferença em relação à via de acesso para a esofagectomia, apesar do maior tempo cirúrgico e de permanência hospitalar na via TT. A sobrevida global em 3 e 5 anos também foi maior na TT, possivelmente devido a maior freqüência de estágios iniciais em pacientes submetidos à transtorácica.

Esofagectomia trans-hiatal com esternotomia parcial

A esofagectomia trans-hiatal oferece a vantagem de não necessitar da toracotomia ou toracoscopia. Apresenta a desvantagem de ter que ser realizada, pelo menos em parte, com dissecação romba, às cegas, ocorrendo com frequência lesão pleural, maior sangramento, entre outras complicações. A associação da transecção mediana do diafragma com a esternotomia parcial permite o isolamento do esôfago totalmente sob visão direta. Os autores apresentam a técnica da esofagectomia trans-hiatal com esternotomia parcial.

Cardiovascular responses to microinjection of trans-(±)-ACPD into the NTS were similar in conscious and chloralose-anesthetized rats

The changes in mean arterial pressure (MAP) and heart rate (HR) in response to the activation of metabotropic receptors in the nucleus tractus solitarii (NTS) with trans-(±)-1-amino-1,3-cyclopentanedicarboxylic acid (trans-(±)-ACPD) were evaluated in conscious and anesthetized Wistar, male rats weighing 240-260 g (N = 8). The responses obtained with trans-(±)-ACPD were compared with the responses to L-glutamate (1 nmol/100 nl), since in a previous study we showed that anesthesia converted a pressor response to L-glutamate microinjected into the NTS of conscious rats to a depressor response in the same rats under urethane or chloralose anesthesia. Microinjection of 3 doses of trans-(±)-ACPD (100, 500 and 1000 pmol/100 nl) produced a dose-dependent fall in MAP (range, -20 to -50 mmHg) and HR (range, -30 to -170 bpm) under both conscious and chloralose anesthesia conditions. These data indicate that the cardiovascular responses to the activation of metabotropic receptors by trans-(±)-ACPD are not affected by chloralose anesthesia while the cardiovascular responses to the activation of excitatory amino acid (EAA) receptors by L-glutamate are significantly altered

Effect of all-trans retinoic acid on newly diagnosed acute promyelocytic leukemia patients: results of a Brazilian center

Thirty-seven patients with acute promyelocytic leukemia (APL) were treated with all-trans retinoic acid (ATRA). Patients received 45 mg m-2 day-1 po of ATRA until complete remission (CR) was achieved, defined as: a) presence of less than 5% blasts in the bone marrow, with b) white blood cells >103/mm3, c) platelets >105/mm3 and d) hemoglobin concentration >8 g/dl, with no blood or platelet transfusions. Thirty-one (83.7%) patients achieved CR by day 50, and 75% of these before day 30. Correction of the coagulopathy, achieved between days 2 and 10 (mean, 3 days), was the first evidence of response to treatment. Only one patient had been previously treated with chemotherapy and three had the microgranular variant M3 form. Dryness of skin and mucosae was the most common side effect observed in 82% of the patients. Thrombosis, hepatotoxicity and retinoid acid syndrome (RAS) were observed in 7 (19%), 6 (16%) and 4 (11%) patients, respectively. Thirteen (35%) patients had to be submitted to chemotherapy due to hyperleukocytosis (above 40 x 103/mm3) and six of these presented with new signs of coagulopathy after chemotherapy. Four (11%) patients died secondarily to intracerebral hemorrhage (IH) and two (5.4%) dropped out of the protocol due to severe ATRA side effects (one RAS and one hepatotoxicity). RAS and IH were related strictly to hyperleukocytosis. The reduced use of platelets and fresh frozen plasma probably lowered the total cost of treatment. We conclude that ATRA is an effective agent for inducing complete remission in APL patients.

Trans-sialidase delivered as a naked DNA vaccine elicits an immunological response similar to a Trypanosoma cruzi infection

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, does not synthesize sialic acid, but expresses a trans-sialidase (TS) that catalyzes the transfer of sialic acid from host glycoconjugates to the parasite surface. Here, we review studies that characterize the immune response to the catalytic domain of the enzyme in humans during Chagas' disease or in mice following immunization with the TS gene. In both cases, there are antibodies that strongly inhibit the enzymatic activity and generation of interferon-g-producing T cells.

alpha-Tocopherol enhances tumour growth inhibition by cis-dichlorodiammine platinum (II)

Present studies indicate that alpha-tocopherol enhances the efficacy of cisplatin as demonstrated by inoculation of Dalton's lymphoma cells incubated with either cisplatin (5 or 10 µg/ml) alone or cisplatin + alpha-tocopherol (25 or 50 µg/ml) into C3H/He mice. Tumour cells (3 x 10(6) cells/mouse) incubated with cisplatin grow slowly in syngeneic mice as indicated by the late appearance of tumour. However, mice failed to develop tumour when inoculated with tumour cells incubated with cisplatin + alpha-tocopherol. When the animals were challenged with tumour cells (3 x 10(6) cells/mouse) on the 15th day after the initial inoculation, 30-50% survived more than 60 days, with 10% tumour-free survivors being observed in some groups. Antitumour activity was higher in mice receiving lymphoma cells (3 x 10(6) cells/mouse) preincubated with cisplatin + alpha-tocopherol compared to cisplatin alone. Tumour-bearing mice receiving cisplatin in combination with different concentrations of alpha-tocopherol exhibited significantly higher (P<0.001) intratumour platinum content (123-306%) but without any change in the kidney platinum content as compared to those receiving cisplatin (5 or 10 µg/ml) alone. Enhancement of cisplatin-induced tumour growth inhibition is probably due to the modulation of tumour cell membrane permeability by alpha-tocopherol. alpha-Tocopherol might increase the influx of cisplatin into tumour cells, causing the DNA repair machinery to be less efficient due to increased efficiency of adduct formation in the DNA molecule. This effect of alpha-tocopherol can render cisplatin more effective as an antitumour agent.

The non-palindromic adaptor-PCR method for the identification of the T-cell receptor genes of an interferon-gamma-secreting T-cell hybridomaspecific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen

Cloning of the T-cell receptor genes is a critical step when generating T-cell receptor transgenic mice. Because T-cell receptor molecules are clonotypical, isolation of their genes requires reverse transcriptase-assisted PCR using primers specific for each different Valpha or Vß genes or by the screening of cDNA libraries generated from RNA obtained from each individual T-cell clone. Although feasible, these approaches are laborious and costly. The aim of the present study was to test the application of the non-palindromic adaptor-PCR method as an alternative to isolate the genes encoding the T-cell receptor of an antigen-specific T-cell hybridoma. For this purpose, we established hybridomas specific for trans-sialidase, an immunodominant Trypanosoma cruzi antigen. These T-cell hybridomas were characterized with regard to their ability to secrete interferon-gamma, IL-4, and IL-10 after stimulation with the antigen. A CD3+, CD4+, CD8- interferon-gamma-producing hybridoma was selected for the identification of the variable regions of the T-cell receptor by the non-palindromic adaptor-PCR method. Using this methodology, we were able to rapidly and efficiently determine the variable regions of both T-cell receptor chains. The results obtained by the non-palindromic adaptor-PCR method were confirmed by the isolation and sequencing of the complete cDNA genes and by the recognition with a specific antibody against the T-cell receptor variable ß chain. We conclude that the non-palindromic adaptor-PCR method can be a valuable tool for the identification of the T-cell receptor transcripts of T-cell hybridomas and may facilitate the generation of T-cell receptor transgenic mice.