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Integrum-aineistokoulutuksen 28.9. - 29.9.2011 koulutusmateriaalia

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.

A new climatic periodisation of the Gold and Guinea Coasts in West Africa, 1750-1798 : a reconstruction of the climate during the slave trade era, including an analysis of the climatically facilitated Trans-Atlantic slave trade

Avsikten med studien är att producera den första rekonstruktionen av det västafrikanska klimatet mellan 1750 och 1798. Kunskapen om det västafrikanska klimatet före 1800-talet är till dags dato bristfällig, vilket gör det svårare att förstå framtida klimatvariationer. Det är bristen på instrumentell meteorologisk data (temperatur, regnmängd, och lufttryck), vilket i princip bara täcker det senaste århundradet, som är orsaken till att tidigare klimat är bristfälligt kartlagda. Klimatet och miljön är även sådana att proxydata från ’naturens arkiv’ (såsom t.ex. trädringar) har begränsad användning. Således är historiska dokument, främst från gästande kulturer/nationer/intressenter, innehållande deskriptiv information om vädret och klimatet, klimatforskarens viktigaste källa. Genom att använda tidigare, för det här syftet, oanvända källor påvisade den här undersökningen att klimatet i västra Afrika och Guldkusten (Ghana) har ändrats sedan 1700-talet. Monsunregnen var svagare och kortvarigare, speciellt den sekundära regnperioden under hösten var betydligt svagare än idag. Det förekom kraftiga årliga variationer i monsunregnen, men sett ur längre tidsperspektiv utmärktes torrare och blötare perioder. Studien kunde också visa en viss korrelation mellan det globala väderfenomenet El Niño och regnperiodens intensitet längs med kusten. Flera torrperioder sammanföll med tidigare registrerade El Niño sekvenser. Speciellt slutet av 1760-talet påverkades kraftigt av El Niño och även det globala klimatet verkar ha genomgått graftiga förändringar just dessa år. På basis av den nya klimatrekonstruktionen genomfördes också en jämförelse av klimatets inverkan på den transatlantiska slavhandeln från 1750 till 1798, en fråga som historikerna gjort anspelningar på i över 30 år. Utförseln av slavar från västra Afrika var som kraftigast under 1700-talets andra hälft. Analysen visade att slavhandeln delvis tilltog i samband med klimatanomalierna.

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.

α-Pinene oxide and verbenol oxide isomerizations over heterogeneous catalysts

Terpenes are a valuable natural resource for the production of fine chemicals. Turpentine, obtained from biomass and also as a side product of softwood industry, is rich in monoterpenes such as α-pinene and β-pinene, which are widely used as raw materials in the synthesis of flavors, fragrances and pharmaceutical compounds. The rearrangement of their epoxides has been thoroughly studied in recent years, as a method to obtain compounds which are further used in the fine chemical industry. The industrially most desired products of α-pinene oxide isomerization are campholenic aldehyde and trans-carveol. Campholenic aldehyde is an intermediate for the manufacture of sandalwood-like fragrances such as santalol. Trans-carveol is an expensive constituent of the Valencia orange essence oil used in perfume bases and food flavor composition. Furthermore it has been found to exhibit chemoprevention of mammary carcinogenesis. A wide range of iron and ceria supported catalysts were prepared, characterized and tested for α-pinene oxide isomerization in order to selective synthesis of above mentioned products. The highest catalytic activity in the preparation of campholenic aldehyde over iron modified catalysts using toluene as a solvent at 70 °C (total conversion of α-pinene oxide with a selectivity of 66 % to the desired aldehyde) was achieved in the presence of Fe-MCM-41. Furthermore, Fe-MCM-41 catalyst was successfully regenerated without deterioration of catalytic activity and selectivity. The most active catalysts in the synthesis of trans-carveol from α-pinene oxide over iron and ceria modified catalysts in N,N-dimethylacetamide as a solvent at 140 °C (total conversion of α-pinene oxide with selectivity 43 % to trans-carveol) were Fe-Beta-300 and Ce-Si-MCM-41. These catalysts were further tested for an analogous reaction, namely verbenol oxide isomerization. Verbenone is another natural organic compound which can be found in a variety of plants or synthesized by allylic oxidation of α-pinene. An interesting product which is synthesized from verbenone is (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol. It has been discovered that this diol possesses potent anti-Parkinson activity. The most effective way leading to desired diol starts from verbenone and includes three stages: epoxidation of verbenone to verbenone oxide, reduction of verbenone oxide and subsequent isomerization of obtained verbenol oxide, which is analogous to isomerization of α-pinene oxide. In the research focused on the last step of these synthesis, high selectivity (82 %) to desired diol was achieved in the isomerization of verbenol oxide at a conversion level of 96 % in N,N-dimethylacetamide at 140 °C using iron modified zeolite, Fe-Beta-300. This reaction displayed surprisingly high selectivity, which has not been achieved yet. The possibility of the reuse of heterogeneous catalysts without activity loss was demonstrated.

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.

Trans fatty acid intake is associated with insulin sensitivity but independently of inflammation

High saturated and trans fatty acid intake, the typical dietary pattern of Western populations, favors a proinflammatory status that contributes to generating insulin resistance (IR). We examined whether the consumption of these fatty acids was associated with IR and inflammatory markers. In this cross-sectional study, 127 non-diabetic individuals were allocated to a group without IR and 56 to another with IR, defined as homeostasis model assessment-IR (HOMA-IR) >2.71. Diet was assessed using 24-h food recalls. Multiple linear regression was employed to test independent associations with HOMA-IR. The IR group presented worse anthropometric, biochemical and inflammatory profiles. Energy intake was correlated with abdominal circumference and inversely with adiponectin concentrations (r = -0.227, P = 0.002), while saturated fat intake correlated with inflammatory markers and trans fat with HOMA-IR (r = 0.160, P = 0.030). Abdominal circumference was associated with HOMA-IR (r = 0.430, P < 0.001). In multiple analysis, HOMA-IR remained associated with trans fat intake (β = 1.416, P = 0.039) and body mass index (β = 0.390, P < 0.001), and was also inversely associated with adiponectin (β = -1.637, P = 0.004). Inclusion of other nutrients (saturated fat and added sugar) or other inflammatory markers (IL-6 and CRP) into the models did not modify these associations. Our study supports that trans fat intake impairs insulin sensitivity. The hypothesis that its effect could depend on transcription factors, resulting in expression of proinflammatory genes, was not corroborated. We speculate that trans fat interferes predominantly with insulin signaling via intracellular kinases, which alter insulin receptor substrates.

Essential oil of Lippia alba and its main constituent citral block the excitability of rat sciatic nerves

Lippia alba is empirically used for infusions, teas, macerates, and hydroalcoholic extracts because of its antispasmodic, analgesic, sedative, and anxiolytic effects. Citral is a mixture of trans-geranial and cis-neral and is the main constituent of L. alba essential oil and possesses analgesic, anxiolytic, anticonvulsant, and sedative effects. The present study evaluated the effects of the essential oil of L. alba (EOLa) and citral on compound action potentials (CAPs) in Wistar rat sciatic nerves. Both drugs inhibited CAP in a concentration-dependent manner. The calculated half-maximal inhibitory concentrations (IC50) of peak-to-peak amplitude were 53.2 µg/mL and 35.00 µg/mL (or 230 µM) for EOLa and citral, respectively. Peak-to-peak amplitude of the CAP was significantly reduced by 30 µg/mL EOLa and 10 µg/mL citral. EOLa and citral (at 60 and 30 µg/mL, values close to their respective IC50 for CAP blockade) significantly increased chronaxy and rheobase. The conduction velocity of the first and second CAP components was statistically reduced to ∼86% of control with 10 µg/mL EOLa and ∼90% of control with 3 µg/mL citral. This study showed that EOLa inhibited nerve excitability and this effect can be explained by the presence of citral in its composition. Both EOLa and citral showed inhibitory actions at lower concentrations compared with other essential oils and constituents with local anesthetic activity. In conclusion, these data demonstrate that EOLa and citral are promising agents in the development of new drugs with local anesthetic activity.

CONFIRMAÇÃO DA IDENTIDADE DA alfa-CRIPTOXANTINA E INCIDÊNCIA DE CAROTENÓIDES MINORITÁRIOS PROVITAMÍNICOS A EM VERDURAS FOLHOSAS VERDES

Numerosos trabalhos comprovaram que os carotenóides principais de folhas verdes são invariavelmente luteína, beta-caroteno, violaxantina e neoxantina. No entanto, há discordância em torno dos carotenóides minoritários. Portanto, a espectrometria de massas por impacto de elétrons e cromatografia líquida de alta eficiência com detector de arranjo de diodos foram utilizados para confirmar a identidade de carotenóides minoritários com atividade provitamínica A em verduras folhosas brasileiras. Os carotenóides pró-vitamínicos A, incluindo os isômeros cis e trans de beta-caroteno, foram separados em coluna de C18 polimérica, Vydac 201TP54, com metanol/água (98:2) como fase móvel. Os espectros UV-visível e de massas confirmaram o carotenóide monoidroxilado como sendo alfa-criptoxantina e não beta-criptoxantina como aponta a literatura internacional. Todas as onze folhas analisadas (agrião, alface crespa, alface lisa, almeirão, caruru, chicória, couve, espinafre, rúcula, salsinha e taioba) apresentaram alfa-criptoxantina, 13-cis-beta-caroteno e 9-cis-beta-caroteno, enquanto que alfa-caroteno foi encontrado em apenas quatro folhas (caruru, couve, salsinha e taioba).

Determination of trans-10-hydroxy-2-decenoic acid (10-HDA) in royal jelly from São Paulo State, Brazil

The 10-HDA content in Brazilian samples (São Paulo State) of royal jelly (RJ) was analyzed using an HPLC method based on the work by BLOODWORTH et al. [2]. The chromatographic conditions were: isocratic system, reversed phase C18-H column, auto sampler, diode array UV-VIS detector adjusted to 225nm, mobile phase composed by methanol/water (45:55) at pH= 2.5 adjusted with phosphoric acid; a-naphtol was used as internal standard, and the running time was 30min. By statistical analysis of the results, the 10-HDA contents of the samples analyzed seem to have two ranges: 1.8% and 3% (w/w), that would be useful to qualify the RJ. This is the first data regarding 10-HDA content of Brazilian RJ.