Rationale Many studies demonstrate down-regulation of the norepinephrine transporter (NET) by desipramine (DMI) in vitro and in stress-naive rats. Little is known regarding regulation of the NET in stressed animals. Objective The present study was designed to investigate effects of DMI on the expression of NET and protein kinases in the stress rat. Methods Adult Fischer 344 rats were subjected to chronic social defeat (CSD) for 4 weeks. DMI (10 mg/kg, intraperitoneal (i.p.)) was administered concurrently with CSD or 1 or 2 weeks after cessation of CSD. Sucrose consumption, NET expression, and protein kinases were measured. Results CSD significantly increased messenger RNA (mRNA) and protein levels of NET in the locus coeruleus, as well as NET protein levels in the hippocampus, frontal cortex, and amygdala. These effects were nearly abolished when DMI was administered concurrently with CSD. CSD-induced upregulation of NET expression in the locus coeruleus, hippocampus, and amygdala lasted at least 2 weeks after cessation of CSD, an effect that was significantly attenuated by 1 or 2 weeks of DMI treatment starting from cessation of the CSD. Concurrent administration of DMI with CSD did not markedly interfere with CSD-induced decreases in protein levels of protein kinases A and C in these brain regions, but it did reverse the CSD-induced reduction in phosphorylated cAMP response element-binding (pCREB) protein levels in most brain regions. Conclusion These findings suggest that NET regulation by DMI occurs in both stressed and behaviorally naive rats, and DMI-induced changes in pCREB may be involved.

Class I antiarrhythmic drugs, such as lidocaine, quinidine and procainamide, are known to be effective membrane stabilizers. However, the mechanism of such "membrane stabilization" has not been elucidated. In the present study we found that all three drugs are powerful scavengers of hydroxyl! radical. In addition, lidocaine was found to be a quencher of singlet oxygen. These drugs are also found to inhibit NADPH-dependent lipid peroxidation in bovine lung microsomes in a dose dependent manner. Since oxyradicals are implicated in the lipid peroxidation process and antiarrhythmic drugs were found to scavenge/quench reactive oxygen species, we proposed that the membrane Stabilizing effects of antiarrhythmic drugs may, in part, be due to their antioxidant properties. Ischemia-reperfusion injury has been studied in many organs. Despite the evidence of functional, metabolic and structural abnormalities during reperfusion, the precise mechanism of reperfusion lung injury remains obscure. Data from the organ models suggest that toxic oxygen metabolites play an important role in the mechanism of reperfusion tissue injury. Lidocaine has also been shown to be clinically valuable for the treatment and prevention of ventricular arrhythmia occurring after surgical correction of myocardial infraction. We found that the class I antiarrhythmic drugs are effective in ameliorating post-ischemic lung reperfusion injury in an ex vivo perfused rat lung model exposed to both normoxic and hyperoxic conditions. Since phagocytes are known to generate reactive oxygen species and play an important role in causing irreversible oxidative tissue injury during reperfusion of organs, we examined the role of antiarrhythmic agents on macrophage function. We found that these drugs inhibit superoxide and hydrogen peroxide production in stimulated macrophages in a dose dependent manner. The diminished production of superoxide was found to be not due to the inactivation of superoxide generating NADPH-oxidase enzyme but by inhibition of the phagocytosis process by these drugs The results of these studies indicate that the antiarrhythmic drugs, such as, lidocaine, quinidine and procainamide, are effective antioxidants and can protect biomembranes against lipid peroxidation injury and post-ischemic reperfusion injury of the lung. We have investigated the mechanism(s) of action of these drugs in ameliorating oxidative tissue injury and found that these drugs are not only effective in removing reactive oxygen species but also cause inactivation of pulmonary macrophage from inappropriately generating reactive species of oxygen. The fundamental knowledge derived from these Studies could lead to enhanced functional improvement of patients following cardiopulmonary bypass, pulmonary arterial embolectomy and acute respiratory distress syndrome, all of which undergo a period of elective/induced ischemia and reperfusion or oxidative stress. / Ph. D.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 5 uppsatser.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-09-14T11:30:48Z No. of bitstreams: 1 eduardoluizmendoncamartins.pdf: 956113 bytes, checksum: e8e88eb48b6a69981a3291e3d3744bcc (MD5) / Approved for entry into archive by Diamantino Mayra (mayra.diamantino@ufjf.edu.br) on 2016-09-26T20:17:11Z (GMT) No. of bitstreams: 1 eduardoluizmendoncamartins.pdf: 956113 bytes, checksum: e8e88eb48b6a69981a3291e3d3744bcc (MD5) / Made available in DSpace on 2016-09-26T20:17:11Z (GMT). No. of bitstreams: 1 eduardoluizmendoncamartins.pdf: 956113 bytes, checksum: e8e88eb48b6a69981a3291e3d3744bcc (MD5) Previous issue date: 2011-03-28 / A obesidade é um grave problema de saúde pública em nosso país, com sua prevalência crescendo em níveis epidêmicos. O grau de obesidade está diretamente relacionado com o risco de morbimortalidade. O tratamento farmacológico deve ser precedido de uma mudança de hábitos alimentares e prática regular de atividades físicas. Os medicamentos só devem ser utilizados sob supervisão médica e após uma avaliação criteriosa da relação risco-benefício, para cada paciente especificamente. Em 2005, o Brasil foi o maior consumidor mundial per capita de anfetaminas com finalidade emagrecedora. Estudos anteriores sugerem que as farmácias de manipulação são responsáveis pela maior porcentagem de notificações referentes a supressores de apetite. O presente estudo avalia as dispensações de psicotrópicos anorexígenos durante o ano de 2009 em Juiz de Fora, por meio das informações obtidas dos boletins de consumo enviados mensalmente (RMNRB2) à VISA municipal e de dados obtidos no SNGPC (ANVISA). De 7.759 notificações de psicotrópicos anorexígenos, 93,3% foram dispensadas por farmácias de manipulação e somente 6,7% por drogarias. Do total, 55,4% foram da substância anfepramona, seguido de 33,1% referentes à femproporex e 11,5% de mazindol. Dos 189 médicos que emitiram as prescrições analisadas, 57% não tinham especialidade cadastrada no CRM. Sete profissionais foram responsáveis por 6.492 dispensações no ano, correspondendo a 83,7% do total. O profissional com maior número de prescrições teve 3.535 prescrições dispensadas, correspondendo a 45,6% de todas as prescrições do período analisado. Das 3.535 prescrições de substâncias psicotrópicas anorexígenas emitidas por esse profissional, todas foram dispensadas em farmácias, sendo 99,5% em um único estabelecimento. As prescrições desse profissional correspondem a 94,3% de todo o movimento de dispensações de anorexígenos efetuadas no período analisado, nesse estabelecimento. Comparando com o relatório da ANVISA referente ao consumo no país, no mesmo período, as três substâncias apresentam um consumo maior em Juiz de Fora e microrregião, em Dose Diária Definida/mil habitantes/ano. O cenário mostra a dispensação de psicotrópicos anorexígenos como um problema relevante de saúde coletiva e indica a necessidade de reavaliação dos critérios de monitoramento de sua prescrição, dispensação e consumo. / Obesity is a serious public health problem in Brazil, with prevalence figures increasing at epidemic rates. The degree of obesity is directly related to the risk of morbidity and mortality. A pharmacological approach must always be preceded by a change of eating habits along with the regular practice of physical exercises. Drugs should only be used under medical supervision and after a careful assessment of the individualized risk-benefit ratio. In 2005, Brazil had the world´s largest per capita consumption of amphetamines for weight loss. Previous studies have suggested that magistral pharmacies are responsible for the largest percentage of notifications referring to appetite suppressants. This study assesses the dispensations of appetite-suppressant psychotropics during the year 2009, in Juiz de Fora, through information obtained from the municipal sanitary surveillance authority (consisting of monthly consumption bulletins [RMNRB2] and data from the Brazilian sanitary surveillance agency [ANVISA]). Of the 7,759 notifications of drugsuppressant psychotropics, 93.3% were dispensed by magistral pharmacies, while only 6.7% were dispensed by drugstores. Of the total, 55.4% were of amphepramone, followed by 33.1% of fenproporex and 11.5% of mazindol. The large majority of the prescribing physicians did not have their specialty registered with the Regional Medical Council (57%). Seven physicians were responsible for 6,492 dispensed prescriptions, accounting for 83.7% of the total. A single physician had been responsible for 3,535 dispensed prescriptions, corresponding to 45.6% of all prescriptions during the study period. Of the 3,535 prescriptions of appetitesuppressant psychotropics signed by this physician, 99.5% were dispensed by a single magistral pharmacy. The prescriptions signed by this physician corresponded to 94.3% of all appetite-suppressants dispensed by this pharmacy during the study period. Compared with the ANVISA report, referring to the national consumption during the same period, the three substances had a greater consumption in Juiz de Fora (daily defined dose/thousand inhabitants/year). This scenario points to the dispensation of appetite-suppressant psychotropics as a relevant public health issue, indicating the need to reassess the criteria guiding the monitoring of their prescription, dispensation and consumption.

[pt] Os minérios de cobre-molibdênio são beneficiados juntos normalmente pelo processo de flotação com a ajuda de coletores sulfidrílicos de relativa seletividade. Os concentrados bulk obtidos devem ser processados com o intuito de remover aqueles coletores empregados, pois eles são prejudiciais na etapa de separação por flotação diferencial, ou seja, na obtenção de concentrados de molibdênio de alta qualidade com baixos conteúdos de cobre e ferro. O processo de flotação bulk é realizado em condições oxidantes na presença de coletores sulfidrílicos (xantatos, etc.). Na prática industrial na etapa de flotação diferencial, estes concentrados bulk são separados por modificação do potencial eletroquímico da polpa para valores considerados redutores -300 a -450 mV, com hidrosulfeto de sódio (NaSH) ou o reagente Nokes (Penta-sulfeto de fósforo dissolvido em hidróxido de sódio) além de cianeto de sódio em alguns dos casos, para melhorar a eficiência do processo. Neste quadro, o processo industrial de separação seletiva produz efluente e gases perigosos como o H2S e HCN que devem ser controlados adequadamente. Este trabalho visa avaliar o uso do reagente ácido pseudo glicol tiouréia (PGA) e ácido tioglicólico (TGA) como alternativas ao processo industrial voltado para a separação seletiva dos minerais de cobre e molibdênio. Para a avaliação do depressor foram empregadas medições de ângulo de contato, potencial zeta, testes de flotação em célula Partridge-Smith (PS), FTIR e testes em célula de bancada em um planejamento experimental. O reagente estudado apresentou boas propriedades depressoras para minerais de cobre. Nos resultados das medições de ângulo de contato, pelo método de bolha cativa, foram encontrados valores maiores para a calcopirita do que para a molibdenita (até 10 graus de diferença) e medidas entre 60 e 70 graus, porém no pH ácido esta diferença diminui e os dois minerais apresentam quase o mesmo ângulo de contato 60 mais ou menos 1 grau. Nas medidas efetuadas não foi empregado o coletor final (querosene) para a molibdenita devido a sua falta de homogeneidade na emulsão para realizar as medidas de ângulo de contato. Nos testes de flotabilidade na célula PS em misturas binarias de calcopirita-molibdenita foram encontradas na faixa ácida, valores de pH nos quais há melhores relações de concentração e recuperações, na ordem de 67 por cento para a molibdenita e apenas 10 por cento para a calcopirita no produto flutuado. Os resultados usando o reagente NaSH em condições similares apresentam recuperações similares de molibdenita, mas na faixa básica do pH. Baseados nestes resultados foram avaliadas diversas variáveis e gerado um planejamento experimental para passar à escala de bancada onde foram obtidas recuperações de 84 por cento no concentrado rougher com apenas 13 por cento de cobre corroborando as boas propriedades do depressor estudado. / [en] Copper-molybdenum porphyry deposits worldwide are exploited industrially by flotation of the ores of interest into a BULK concentrate with the aid of sulfhydryl collectors of high efficiency and low selectivity. The bulk concentrate obtained should be reprocessed in order to remove those collectors employed in the bulk stage since they impair the differential flotation during the separation step in order to obtain clean high quality molybdenite concentrates at low contents of copper and iron. The bulk flotation process is conducted under oxidizing conditions in presence of sulfhydryl collectors (xanthates, etc.). In industrial practice these bulk concentrates are then separated by modification of the pulp electrochemical potential to values considered reducing, between -300 to-450 mV, with sodium hidrosulphide (NaSH) or Nokes reagent (phosphorus pentasulfide dissolved in sodium hydroxide). Addition of sodium cyanide in some cases is used to improve process efficiency. Bulk concentrates produced are however a very small portion of the processed mineral (only 1/50 of the total ore milled), these industrial processes produce waste effluents and hazardous gases such as H2S and HCN if not adequately controlled. This dissertation seeks to assess the reagent pseudo glycol tiourea acid (PGA) and thioglycolic acid (TGA) as an alternative to industrial processing for the selective separation of minerals of copper and molybdenum. On the evaluation of this depressant were used contact angle measurements, zeta potential, flotation tests in Partridge-Smith cell (PS), FTIR and bench scale flotation testing cell with an experimental design. The reagent studied showed good depressant properties for copper minerals according to the results presented. Within the results of the contact angle measurements with the captive bubble technique were found greater contact angles for chalcopyrite than for molybdenite (up to 10 degrees difference) and values between 60 and 70 degrees, however in acidic pH this difference decreases and both minerals have almost the same contact angle as of 60 more or less 1 degree. Though on the contact angle measured values it was not employed the final collector (kerosene) for molybdenite due to lack of homogeneity on emulsions to make the contact angle measurements. On floatability tests (on PS cell) with binary mixtures of chalcopyrite-molybdenite were found pH values on the acidic range, at which good concentration ratios and recoveries in the order of 67 percent of molybdenite with only 10 percent of the chalcopyrite were obtained. The results using NaSH reagent under similar conditions gave similar recoveries for molybdenite, however it was found in the basic pH range. Based on the results, several variables were evaluated and an experimental design employed on bench scale flotation tests, the results showed recoveries of 84 percent were obtained in the rougher concentrate with 13 percent copper corroborating the good properties of this depressant.

No description available.

Made available in DSpace on 2015-07-22T20:50:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-05-27 / Introdução/Objetivo: Os fatores orexígenos e anorexígenos e a Taxa Metabólica de Repouso (TMR) desenvolvem um importante papel no controle e regulação do balanço energético e estão diretamente relacionados com a obesidade. Com base nesta relação, o objetivo desta pesquisa foi verificar os efeitos do tratamento multidisciplinar de longo prazo nos fatores orexígenos e anorexígenos e na TMR em adolescentes obesos. Metodologia: No presente estudo foram selecionados 20 adolescentes obesos (11 meninas e 9 meninos), com idade entre 14 e 19 anos. Os critérios de inclusão foram o IMC percentil > 95 de acordo com o Centers for Disease Control and Prevention e estágio de maturação sexual pós púbere. Os fatores orexígenos e anorexígenos foram avaliados por radioimunoensaio. A TMR foi mensurada por calorimetria indireta, a composição corporal por Pletismografia e a gordura visceral e subcutânea por Ultra-sonografia. Resultados: Após 12 meses de intervenção, os adolescentes obesos apresentaram diminuição significativa na massa corporal total, no IMC, na gordura corporal (% e em kg,), na massa magra (kg), e na gordura visceral e subcutânea. O grupo não apresentou diminuição significativa da TMR. Os fatores anorexígenos diminuíram significativamente e o MCH aumentou ao término da terapia. Conclusão: Podemos concluir que a terapia multidisciplinar de longo prazo foi efetiva para melhorar a composição corporal, os fatores orexígenos e anorexígenos, contribuindo para o controle da obesidade e do balanço energético. Palavras-Chave: Fatores orexígenos e anorexígenos; taxa metabólica de repouso; adolescente obeso; terapia multidisciplinar. / Background/Aims: anorexigenic and orexigenic factors and resting metabolic rate (RMR) play an important role in the energy balance and they are directly related to obesity. In this way, it was verified the effects of long-term multidisciplinary therapy on orexigenic and anorexigenic factors and resting metabolic rate in obese adolescents. Methods: Twenty obese adolescents (11 girls and 9 boys) aged between 14 and 19 years, BMI > 95th percentile of CDC, were submitted to intensive long-term multidisciplinary therapy during 12 months. Orexigenic and anorexigenic factors concentrations were measured by a radioimmunoassay (RIA) kit. RMR was measured by indirect calorimetry. Body composition was measured by pletismography, and visceral and subcutaneous fat were analyzed by ultrassonography. Results: After one year of multidisciplinary therapy, the obese adolescents presented a significant decrease in body mass (p<0.001), BMI (p<0.001), fat mass (kg and %), lean mass (kg), subcutaneous and visceral fat. The group did not decrease significantly in RMR and RMR/FFM. The anorexigenic factors (leptin and alpha- MSH concentrations) decreased significantly. The orexigenic neuropeptide (MCH) increased by the end of the multidisciplinary therapy. Conclusion: Our investigation demonstrated that long-term multidisciplinary therapy was effective to improve body composition, anorexigenic and orexigenic factors contributing to obesity control. / TEDE / BV UNIFESP: Teses e dissertações