O objetivo do presente estudo foi o de determinar os efeitos da exposição prolongada ao KCN e ao KSCN em ratos, no período perinatal. Inicialmente, realizou-se o estudo toxicocinético do tiocianato em ratas, em três estados fisiológicos diferentes: fase estrogênica, gestacional e de lactação. Para tal, estes animais receberam, por via oral, na água de bebida ou gavage, a dose única de 3 mg/kg de KCN. Os resultados obtidos mostraram aumento significante nos níveis séricos, lácteos e no líquido amniótico, de tiocianato, após a administração do KCN. A partir destes dados, foram calculados os parâmetros toxicocinéticos. Na segunda etapa, foram utilizadas ratas, as quais foram divididas em 3 grupos controles e 18 experimentais, que receberam as diferentes doses de KCN (1; 3 e 30 mg/kg) ou KSCN (0,8; 2,4 e 24 mg/kg), na água de bebida, do 6º ao 20º dia de gestação e submetidas à eutanásia no 20º dia da gestação ou no 22º dia pós-parto; e do 1º ao 19º dia da lactação, e submetidas à eutanásia no 19º dia deste período. Ao final de cada experimento, os animais foram submetidos à eutanásia, no período apropriado, bem como os fetos e filhotes, coletando-se soro para análise dos níveis de tiocianato, glicose, colesterol, uréia, creatinina, alanina aminotransferase, aspartato aminotransferase, fosfatase alcalina, bem como foram retirados fragmentos do sistema nervoso central, do rim, do pâncreas, da tireóide, do fígado, do pulmão e do baço para estudo histopatológico. Ainda, realizou-se a dosagem de tiocianato no líquido amniótico e no leite, bem como a análise óssea e visceral dos fetos. Dos parâmetros bioquímicos analisados, em relação às mães, verificou-se que os níveis séricos de tiocianato estiveram aumentados, significantemente, em diversos grupos experimentais, no entanto, poucas foram as alterações nas enzimas e outras substâncias avaliadas. O estudo histológico revelou, tanto naquelas gestantes quanto nas lactantes, nefrose, hemorragia e hemossiderose renal; congestão, neuronofagia e gliose no SNC; congestão, vacuolização e proliferação dos ductos biliares e aumento no número de vacúolos de reabsorção no colóide dos folículos tireoidianos, de forma dose-dependente, nos diferentes grupos experimentais. Ratas gestantes, submetidas à eutanásia no 20º dia da gestação apresentaram, ainda, depleção de células das ilhotas de Langerhans. Em relação aos filhotes, tanto aqueles provenientes de fêmeas tratadas durante a gestação quanto da lactação, verificou-se que, embora a avaliação bioquímica tenha revelado alteração apenas no tiocianato sérico de filhotes de mães provenientes dos grupos experimentais, o estudo histológico, nestas proles, mostrou várias lesões, a saber: congestão, neuronofagia e gliose no SNC, congestão renal e hepática, vacuolização e proliferação dos ductos biliares. Por outro lado, não foram detectadas alterações na performance reprodutiva bem como na análise visceral e óssea dos fetos. Portanto, pode-se sugerir que o cianeto e/ou seu metabólito promovam efeito tóxico diretamente sobre o feto, no entanto estas alterações são passíveis de detecção apenas na fase pós-natal. Além disto, verificou-se, que o cianeto e/ou o tiocianato são carreados para o leite, podendo comprometer, também, a saúde do neonato. / The aim of the present study was to determinate the toxic effects of long-term exposure to KCN and KSCN in rats, during perinatal period. Initially, it was achieved the toxicokinetics study of the thiocyanate in female rats, in three different physiological states: estrogenic, gestation and lactation. These animals received, per os, in the drinking water or by gavage, the unique dose of 3.0 mg KCN/kg. The results showed significantly increased in the thiocyanate levels in the serum, milk and amniotic fluid, after the administration of the KCN. The toxicokinetics parameters were calculated based on these data. In a second part, female rats were distributed in 18 experimental and 3 control groups. The experimental groups were dosed with 1, 3 and 30 mg KCN/kg or 0.8; 2.4 and 24 mg KSCN/kg, daily, in the drinking water, from days 6 to 20 of gestation and euthanized on day 20 of gestation or on day 22 postpartum; or received from days 1 to 19 of lactation and euthanized on day 19 of lactation. At the end of each experiment, the animals were euthanized, in the appropriated period, as well as the fetuses and pups. The serum samples were obtained in order to determine the thiocyanate, glucose, cholesterol, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase levels as well as samples of the following organs for the histopathological study: central nervous system, kidney, pancreas, thyroid, liver, lung and spleen. Yet, the levels of thiocyanate were evaluated in the amniotic fluid and milk, from the mothers, as well as the skeletal and visceral analysis of the fetuses. From the biochemical parameters, in relation to the dams, it was verified that the thiocyanate levels were significantly increased, in several experimental groups; otherwise, too few alterations were observed in the enzymes and others substances analyzed. The histopathological study revealed, in the pregnant and lactating rats, nephrosis, hemorrhage and hemosiderosis in the kidneys; congestion, neuronophagia and gliosis in the CNS; vacuolization and proliferation of the biliar ducts in the liver and increase in the number of reabsorption vacuoles in follicular colloid, in a dose-dependent manner, in some experimental groups. At the pregnant rats that were euthanized on day 20 of gestation, it was verified depletion of cells from the islets of Langerhans. In relation to the pups, from mothers exposed during the gestation and lactation, it was verified alteration in the thiocyanate levels from experimental groups and the histopathological study revealed: congestion, neuronophagia and gliosis in the CNS, renal and hepatic congestion, vacuolization and proliferation of biliar ducts. On the other hand, it was verified no alterations in the reproductive performance nor skeletal and visceral analysis of the fetuses. Thus, it was suggested that the cyanide and/or its metabolite promoted toxic effect straight to the fetuses; however, these alterations are susceptible of detection only at postnatal phase. Furthermore, the cyanide and/or thiocyanate are transferred to the breast milk of rats and can also compromise the health of the offspring.

Made available in DSpace on 2016-04-28T20:17:25Z (GMT). No. of bitstreams: 1 2007- Thalita Gagini Braga.pdf: 8852629 bytes, checksum: e6a948ca864bea46a3f48309716903c7 (MD5) Previous issue date: 2007-03-05 / Made available in DSpace on 2016-04-28T20:17:25Z (GMT). No. of bitstreams: 1 2007- Thalita Gagini Braga.pdf: 8852629 bytes, checksum: e6a948ca864bea46a3f48309716903c7 (MD5) Previous issue date: 2007-03-05 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Piperine (1- piperoyl piperidine) main black pepper (Pipper nigrum Linn.) and long pepper (Piper longum Linn.) alkaloid presents several pharmacological and biochemical effects as enzymes inhibition from hepatic metabolism interfering on xenobiotics and pro-carcinogenic substances biotransformation activated by P-450 cytochromo cycle. According to the scientific bibliography reports, piperine has been able in vitro for decreasing cytotoxicity as well as aflatoxin B1 genotoxicity on mice cells through the competition by P-450 cytochromo. Due to the importance of grains contamination by aflatoxinas, this survey had as proposal to verify piperine ability for decreasing in vivo some damages caused by these toxins. On first, at different piperine doses (1,12; 2,25 and 4,50 mg/Kg) Lou-M strain rats groups were inoculated by oral administrated to evaluated this amide toxicity on animal pattern. Parameters as: weight grain, anatomopathological and histopathological analyses beyond changes on hematological values have been researched. Piperine doses (1,12 mg/Kg) has showed to be appropriate as well as safe on biological assays and it has been used on rats experimental intoxication assays by aflatoxins. Three rats groups were inoculated with piperine (1,12 mg/Kg), aflatoxins (72 μg/ 100 g) as well as piperine + aflatoxins according to the same parameters above described. Piperine has been able for interfering in vivo on aflatoxins toxicity, conspicuously decreasing histopathological injuries on intoxicated animals and significantly returning immunosupression mediated by aflatoxins. / A piperina (1-piperoil piperidina), principal amida constituinte da pimenta preta (Piper nigrum Linn.) e da pimenta longa (P. longum Linn.), apresenta diversos efeitos farmacol?gicos e bioqu?micos, como a inibi??o de enzimas do metabolismo hep?tico, interferindo na biotransforma??o de xenobi?ticos e subst?ncias pr?-carcin?genas ativadas pela via do citocromo P450. A literatura descreve a piperina como sendo capaz, in vitro, de diminuir a citotoxidez e a genotoxidez da aflatoxina B1 em c?lulas de ratos, atrav?s da competi??o pelo citocromo P450. Devido ? import?ncia da contamina??o de gr?os por aflatoxinas, este trabalho teve como objetivo verificar a capacidade da piperina em diminuir, in vivo, os danos causados por essas toxinas. Inicialmente, grupos de ratos da linhagem LOUM foram inoculados, via oral, com diferentes doses de piperina (1,12; 2,25 e 4,50 mg/kg de peso corporal), visando avaliar a toxidez dessa amida no modelo animal empregado. Par?metros como: ganho de peso, an?lises anatomopatol?gica e histopatol?gica, al?m das altera??es nos valores hematol?gicos foram investigados. A dose de 1,12 mg/kg de peso corporal de piperina demonstrou ser segura nos ensaios biol?gicos e foi empregada nos ensaios de intoxica??o experimental de ratos com aflatoxinas. Tr?s grupos de ratos foram inoculados com piperina (1,12 mg/kg de peso corporal), aflatoxinas (72 μg/100g de peso corporal) e, piperina + aflatoxinas, sendo avaliados os mesmos par?metros acima descritos. A piperina foi capaz de interferir na toxidez das aflatoxinas, in vivo, diminuindo de forma acentuada as les?es histopatol?gicas evidenciadas nos animais intoxicados e, revertendo de forma significativa a imunossupress?o mediada pelas aflatoxinas.

Ipomoea carnea, planta tóxica da família da Convolvulaceae, possui a suainsonina um alcalóide indolizidínico, o qual promove inibição da enzima α-manosidase ácida ou lisossômica levando ao acúmulo celular de oligossacarídeos não metabolizados adequadamente, causando vacuolização celular. A planta também possui outros alcalóides, as calisteginas que inibem as β-glicosidases, agravando o efeito causado pela suainsonina. O objetivo do presente estudo foi de avaliar as possíveis alterações clínicas, bioquímicas, hematológicas, neuroquímica e patológicas em caprinos tratados com diferentes doses de I. carnea. Foram usados 25 caprinos, divididos em 5 grupos iguais: 4 experimental e 1 controle. Os caprinos dos grupos experimentais receberam durante 4 meses diferentes doses de I. carnea: 2,5; 5,0; 10,0 e 30,0 g/kg/dia. Semanalmente, os animais foram pesados e avaliados clinicamente. Coletou-se sangue da veia jugular, quinzenalmente, para determinação da concentração de glicose, colesterol, alanina transferase (ALT), aspartato transaminase (AST), uréia e creatinina, e mensalmente para a determinação do hemograma. No final do período experimental, todos os caprinos foram submetidos à eutanásia e fragmentos de cérebro, medula espinal, nervo ciático, tireóide, miocárdio, fígado, rim, baço, pulmão, pâncreas e intestinos foram coletados e fixados para estudo anatomopatológico. Os resultados mostraram que os animais experimentais apresentavam nistagmo, tremores musculares, fraqueza dos membros pélvicos, incoordenação motora e ataxia. O estudo bioquímico revelou que os animais experimentais apresentaram menores níveis de glicose e aumento nos níveis de AST, ALT e creatinina. O estudo hematológico mostrou significante redução nos níveis de hemácias, hemoglobina e hematócrito. A histopatologia revelou alterações vacuolares no fígado, pâncreas, tireóide, células renais e em neurônios do sistema nervoso central. Os resultados apresentados permitem concluir, que a ingestão da I. carnea produz toxicidade para a espécie caprina de forma dose-dependente. / Ipomoea carnea, a shrub plant of Convolvulaceae family, possess swainsonine, an indolizidinic alkaloid, which promotes cellular accumulation of not metabolized oligossacarides, due to inhibition of acid or lisossomal α-manosidasis enzyme, causing cellular vacuolization. The plant also has other alkaloid, the calystegein, which inhibits β-glicosidase, aggravating the effect of the swainsonine. The objective of the present study was to evaluate the possible clinical, biochemical, hematological, pathological and neurochemistry alterations in goat treated with different doses of green leaves of the Ipomoea carnea. It was used 25 goats, divided in 5 equal groups: 4 experimental and 1 control. Goats from experimental groups received, during 4 months the different doses of Ipomoea carnea: 2,5; 5,0; 10,0 and 30,0 9 of plantlkg of live weight Iday. Weekly, the animais were weighted and evaluated clinically. Before the experimental period and every other week blood samples were taken from jugular vein in order to determine the and the concentration of the glucose, cholesterol, alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), blood urea nitrogen (BUN), and creatinina, and every month to determinate the hemogram. At the end of the experimental period, ali the goats were killed and fragments from brain, spinal cord, sciatic nerve, thyroids, myocardium, liver, kidney, spleen, lung, pancreas, intestine were collect, fixed in 10% formalin and routinely embedded in paraffin. Results showed that the animais from ali experimental groups presented nystagmus, muscular tremors, weakness of the hind limbs, incoordination of movement and ataxia. The biochemical study revealed that these animais presented significant increase in the AST, ALT and creatinine levels, when compared with goats from control group. The hematological study showed significant reduction in the levels of hemoglobin, and hematocrit in ali goats that had been treated with Ipomoea carnea. The histopathology revealed degenerative vacuolar alterations of liver, pancreas, thyroid, kidneys cells and in the neurons of the central nervous system in animais that received the plant and these alterations were more prominent in goats treated with the higher dose of I.carnea. Thus, the results presented here permit to conclude that the ingestion of Ipomoea carnea, is certainly toxic in goat production.

Submitted by Sandro Camargo (sandro.camargo@unipampa.edu.br) on 2015-03-09T01:24:09Z No. of bitstreams: 1 116110007.pdf: 1272424 bytes, checksum: f522c931abce90928d851acf99e14fdf (MD5) / Made available in DSpace on 2015-03-09T01:24:09Z (GMT). No. of bitstreams: 1 116110007.pdf: 1272424 bytes, checksum: f522c931abce90928d851acf99e14fdf (MD5) Previous issue date: 2012-02-27 / A zearalenona (ZEA) é produzida por fungos da espécie Fusarium, e sua ocorrência é freqüente em grãos e cereais em todo o mundo. A ZEA é estruturalmente semelhante ao estrogênio, e, portanto, é responsável pela síndrome estrogênica, uma vez que possui capacidade de ativar os receptores de estrogênio provocando alterações funcionais dos órgãos do trato reprodutivo. Além disso, como uma micotoxina toxigênica e imunosupressora, altera parâmetros hematológicos e promove um desequilíbrio no sistema oxidativo, especialmente nas enzimas antioxidantes. Assim, o objetivo do nosso trabalho é avaliar os efeitos agudos causados pela administração oral de ZEA. Foram utilizados camundongos Swiss machos que receberam uma administração de ZEA (40 mg/kg), e após 48 horas foram submetidos a eutánasia. Como parâmetros de toxicidade, foram analisados os pesos dos órgãos (pulmão, fígado, baço, rins, testículos e epidídimos), análise comportamental, dosagem de parâmetros hematológicos pela contagem de leucócitos totais, frações (segmetados, bastões, eosinófilos, monócitos e linfócitos) e plaquetas, parâmetros reprodutivos pela contagem de espermatozóides e análise da motilidade e parâmetros do sistema oxidativo pela dosagem das enzimas antioxidantes superóxido dismutase (SOD), catalase (CAT) e glutationa-S-transferase (GST), determinação de ácido ascórbico (AA), determinação de tióis não-proteícos (NPSH) e avaliação da peroxidação lipídica pela determinação das substâncias reativas ao ácido tiobarbitúrico (TBARS). Os resultados mostram que a intoxicação aguda por ZEA causa efeitos hematológicos pelo aumento da contagem total de leucócitos e das frações bem como diminuição da contagem de linfócitos e plaquetas. Os efeitos reprodutivos observados foram a redução significativa do número e motilidade de espermatozóides. Quanto aos parâmetros de estresse oxidativo, a ZEA reduziu a atividade da GST nos testículos e nos rins, a atividade da SOD aumentou nos rins, fígado e testículos, e a atividade da CAT aumentou nos rins. A análise comportamental, a determinação de AA e NPSH assim como, o TBARS não sofreram alterações neste protocolo. Com base nos resultados confirma-se que o sistema reprodutivo é o principal alvo da ZEA, mesmo no protocolo de intoxicação aguda, e que existe uma relação entre o estresse oxidativo, especialmente a redução da atividade da GST, com as alterações espermáticas. Conclui-se que a administração aguda de ZEA induz efeitos tóxicos hematológicose reprodutivos, e provavelmente estes efeitos se relacionam com o estresse oxidativo. / Zearalenone (ZEA) a non-steroidal estrogenic mycotoxin produced by several species of Fusarium, and its occurrence is common in grains and cereals worldwide. ZEA is structurally similar to estrogen, and therefore is responsible for the estrogen syndrome, since it has the ability to activate estrogen receptors, inducing functional changes in the reproductive tract organs. Moreover, as an immunosuppressive mycotoxin it has been demonstrated that elicits hematological and reproductive damage. Therefore, the current study was aimed to investigate the effects of an acute oral dose of ZEA. Adult Swiss albino male mice were exposed to a single oral injection of ZEA (40 mg/kg, p.o.), and 48 hours thereafter behavioral and biochemical tests were performed. In order to evaluate any possible toxic action of acute ZEA administration, the body and vital organs (lung, liver, spleen, kidney, testis and epididymis) relative weight were determined, as well as behavioral analysis, measurement of hematological and reproductive parameters (sperm count and motility). Additionally, markers of oxidative stress in liver, kidney and testes of mice were analysed by measuring the activity of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST). Moreover, determination of ascorbic acid (AA), non-protein thiols (NPSH) and assessment of lipid peroxidation by determination of thiobarbituric acid reactive substances (TBARS) were also analysed. Results show that ZEA caused acute hematological effects by increasing the total leukocyte number and fractions as well as a decreased lymphocyte and platelets number. ZEA drastically reduced the number and motility of live spermatozoa. Regarding the oxidative stress parameters, ZEA reduced the GST activity in the testis and kidney, SOD activity increased in kidney, liver and testis, and CAT activity increased in the kidneys. However, behavioral analysis, determination of AA and NPSH as well TBARS content were not altered by ZEA administration. In summary, we showed that ZEA have acute toxic effects mainly in reproductive system of adult male Swiss albino mice and its effect probably is related to a reduced activity of GST and increased in SOD activity in testes. We conclude that acute administration of ZEA induces hematological and reproductive toxicity, and probably these effects are related to oxidative stress.

Submitted by Sandro Camargo (sandro.camargo@unipampa.edu.br) on 2015-03-09T01:55:05Z No. of bitstreams: 1 116110004.pdf: 1404525 bytes, checksum: ca74119d1b54d005e98448f652e62885 (MD5) / Made available in DSpace on 2015-03-09T01:55:06Z (GMT). No. of bitstreams: 1 116110004.pdf: 1404525 bytes, checksum: ca74119d1b54d005e98448f652e62885 (MD5) Previous issue date: 2012-09-26 / O mercúrio aumenta o risco de doença cardiovascular, estresse oxidativo, e altera a reatividade vascular. Este metal induz disfunção endotelial, como resultado da diminuição da biodisponibilidade de óxido nítrico (NO) por aumento do estresse oxidativo e produção de prostanóides contráteis. A enzima NADPH oxidase é a principal fonte de espécies reativas de oxigênio (ROS) na vasculatura. Nosso objetivo foi investigar se o tratamento com apocinina, um inibidor da NADPH oxidase, evita os efeitos vasculares causados pela intoxicação crônica por baixas concentrações de mercúrio. Para isso, ratos machos Wistar de três meses de idade foram tratados durante 30 dias com: a) Não-tratado (injeções intramusculares - im - de solução salina, b) HgCl 2 (im, primeira dose de 4,6 ug/kg, e doses subsequentes de 0,07 ug/kg/dia), c) Apo (1,5 mM de apocinina em água de beber e salina im); d) ApoHg (tratamento com mercúrio e apocinina) Tratamento com mercúrio: 1) aumentou a resposta vasoconstritora à fenilefrina na aorta e reduziu a resposta dependente do endotélio à acetilcolina, 2) aumentou o envolvimento de ROS e prostanoides vasoconstritores em resposta à fenilefrina enquanto reduziu a modulação de NO endotelial de tais respostas, 3) reduziu a atividade das enzimas superóxido dismutase (SOD) e glutationa peroxidase (GPx) da aorta e aumentou os níveis de malondialdeído (MDA) plasmático. O tratamento com apocinina preveniu parcialmente o aumento da resposta à fenilefrina e reduziu a disfunção endotelial induzida pelo mercúrio. Além disso, aumentou a modulação de NO das respostas vasoconstritoras, a atividade da SOD aórtica e reduziu os níveis plasmáticos de MDA, sem afetar o aumento da participação de prostanóides vasoconstritores observados na aorta de ratos tratados pelo mercúrio. Conclusões: O mercúrio aumenta a resposta vasoconstritora à fenilefrina pela redução da biodisponibilidade de NO e aumenta a participação de ROS e prostanoides vasoconstritores. A apocinina protege o vaso dos efeitos deletérios causados pela NADPH oxidase, mas não dos causados pelos prostanoides, demonstrando a ação de duas vias independentes nos danos cardiovasculares desenvolvidos pelo metal. / Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS) in the vasculature. Our aim was to investigate whether treatment with apocynin, an NADPH oxidase inhibitor, prevents the vascular effects caused by chronic intoxication with low concentrations of mercury. Three-month-old male Wistar rats were treated for 30 days with a) intramuscular injections (i.m.) of saline; b) HgCl 2 (i.m. 1 st dose: 4.6 μg/kg, subsequent doses: 0.07 μg/kg/day); c) Apocynin (1.5 mM in drinking water plus saline i.m.); and d) Apocynin plus HgCl 2 . The mercury treatment resulted in 1) an increased aortic vasoconstrictor response to phenylephrine and reduced endothelium-dependent responses to acetylcholine; 2) the increased involvement of ROS and vasoconstrictor prostanoids in response to phenylephrine, whereas the endothelial NO modulation of such responses was reduced; and 3) the reduced activity of aortic superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increased plasma malondialdehyde (MDA) levels. Treatment with apocynin partially prevented the increased phenylephrine responses and reduced the endothelial dysfunction elicited by mercury treatment. In addition, apocynin treatment increased the NO modulation of vasoconstrictor responses and aortic SOD activity and reduced plasma MDA levels without affecting the increased participation of vasoconstrictor prostanoids observed in aortic segments from mercury-treated rats. Conclusions: Mercury increases the vasoconstrictor response to phenylephrine by reducing NO bioavailability and increasing the involvement of ROS and constrictor prostanoids. Apocynin protects the vessel from the deleterious effects caused by NADPH oxidase, but not from those caused by prostanoids, thus demonstrating a two-way action.

Ipomoea carnea, planta tóxica da família da Convolvulaceae, possui a suainsonina um alcalóide indolizidínico, o qual promove inibição da enzima α-manosidase ácida ou lisossômica levando ao acúmulo celular de oligossacarídeos não metabolizados adequadamente, causando vacuolização celular. A planta também possui outros alcalóides, as calisteginas que inibem as β-glicosidases, agravando o efeito causado pela suainsonina. O objetivo do presente estudo foi de avaliar as possíveis alterações clínicas, bioquímicas, hematológicas, neuroquímica e patológicas em caprinos tratados com diferentes doses de I. carnea. Foram usados 25 caprinos, divididos em 5 grupos iguais: 4 experimental e 1 controle. Os caprinos dos grupos experimentais receberam durante 4 meses diferentes doses de I. carnea: 2,5; 5,0; 10,0 e 30,0 g/kg/dia. Semanalmente, os animais foram pesados e avaliados clinicamente. Coletou-se sangue da veia jugular, quinzenalmente, para determinação da concentração de glicose, colesterol, alanina transferase (ALT), aspartato transaminase (AST), uréia e creatinina, e mensalmente para a determinação do hemograma. No final do período experimental, todos os caprinos foram submetidos à eutanásia e fragmentos de cérebro, medula espinal, nervo ciático, tireóide, miocárdio, fígado, rim, baço, pulmão, pâncreas e intestinos foram coletados e fixados para estudo anatomopatológico. Os resultados mostraram que os animais experimentais apresentavam nistagmo, tremores musculares, fraqueza dos membros pélvicos, incoordenação motora e ataxia. O estudo bioquímico revelou que os animais experimentais apresentaram menores níveis de glicose e aumento nos níveis de AST, ALT e creatinina. O estudo hematológico mostrou significante redução nos níveis de hemácias, hemoglobina e hematócrito. A histopatologia revelou alterações vacuolares no fígado, pâncreas, tireóide, células renais e em neurônios do sistema nervoso central. Os resultados apresentados permitem concluir, que a ingestão da I. carnea produz toxicidade para a espécie caprina de forma dose-dependente. / Ipomoea carnea, a shrub plant of Convolvulaceae family, possess swainsonine, an indolizidinic alkaloid, which promotes cellular accumulation of not metabolized oligossacarides, due to inhibition of acid or lisossomal α-manosidasis enzyme, causing cellular vacuolization. The plant also has other alkaloid, the calystegein, which inhibits β-glicosidase, aggravating the effect of the swainsonine. The objective of the present study was to evaluate the possible clinical, biochemical, hematological, pathological and neurochemistry alterations in goat treated with different doses of green leaves of the Ipomoea carnea. It was used 25 goats, divided in 5 equal groups: 4 experimental and 1 control. Goats from experimental groups received, during 4 months the different doses of Ipomoea carnea: 2,5; 5,0; 10,0 and 30,0 9 of plantlkg of live weight Iday. Weekly, the animais were weighted and evaluated clinically. Before the experimental period and every other week blood samples were taken from jugular vein in order to determine the and the concentration of the glucose, cholesterol, alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), blood urea nitrogen (BUN), and creatinina, and every month to determinate the hemogram. At the end of the experimental period, ali the goats were killed and fragments from brain, spinal cord, sciatic nerve, thyroids, myocardium, liver, kidney, spleen, lung, pancreas, intestine were collect, fixed in 10% formalin and routinely embedded in paraffin. Results showed that the animais from ali experimental groups presented nystagmus, muscular tremors, weakness of the hind limbs, incoordination of movement and ataxia. The biochemical study revealed that these animais presented significant increase in the AST, ALT and creatinine levels, when compared with goats from control group. The hematological study showed significant reduction in the levels of hemoglobin, and hematocrit in ali goats that had been treated with Ipomoea carnea. The histopathology revealed degenerative vacuolar alterations of liver, pancreas, thyroid, kidneys cells and in the neurons of the central nervous system in animais that received the plant and these alterations were more prominent in goats treated with the higher dose of I.carnea. Thus, the results presented here permit to conclude that the ingestion of Ipomoea carnea, is certainly toxic in goat production.

Orientador: Aureo Evangelista Santana / Banca: Edanir dos Santos / Banca: Rosemeri de Oliveira Vasconcelos / Banca: Alessandra Kataoka / Banca: Maria Angélica Dias / Resumo: Neste estudo buscou-se avaliar o uso do Benzeno preparado homeopaticamente em camundongos, no caso de intoxicação experimental aguda pela mesma substância química. Para tanto, foi utilizado um modelo experimental com 45 camundongos, subdivididos em 5 grupos (n=9). Os animais foram tratados durante 15 dias, sendo que o grupo controle recebeu 0,2mL óleo, via intraperitoneal (IP). O grupo branco 0,2mL álcool 30% (IP). Os grupos subseqüentes foram tratados com 0,2mL de Benzenum 6CH, 12CH e 30CH (IP). No 15° dia, administrou-se 3,0422mL/Kg Benzeno em óleo, e amostras de sangue foram colhidas para a realização de hemograma, exames bioquímicos séricos e após o óbito, fragmentos do fígado e dos rins foram colhidos, e o esterno, para a avaliação da medula óssea. As médias dos pesos demonstraram variações estatisticamente significantes, entre os grupos. O hemograma não revelou médias estatisticamente diferentes. Os exames bioquímicos ALT, FA, uréia e creatinina não mostraram resultados estatisticamente diferentes. A taxa de mortalidade foi menor entre os grupos tratados homeopaticamente, sobretudo Benzenum 12 CH. O Benzenum foi capaz de diminuir a mortalidade esperada (DL50 3,0422mL/Kg Benzeno) comprovando a Lei dos Semelhantes, um dos pilares da Homeopatia. / Abstract: This present study aimed to evaluate the use of homeopathically prepared benzene in acute experimentally intoxicated mice with benzene. Five groups with nine mice each were used (n=45). Those animals were pre-treated for 15 days with 0,2mL of oil, intraperitoneally (IP), control group; 0,2mL of alcohol 30%,(IP) -white group; 0,2mL of Benzenum (IP), each, 6CH, 12CH, 30CH, respectively. At the 15th day, the LD50 of Benzene (3,0422mL/kg), and oil was injected, IP, and blood samples were taken for execution of blood, serum biochemical tests. After death, fragments of the liver and kidneys and the sternum, were sent to histopathological evaluation. The mean weights demonstrated statistically significant variations among the groups; The blood did not reveal statistically different media. The examinations biochemical ALT, FA, urea and creatinine showed no statistically different results. The mortality rate was lowest among the groups treated homeopathically especially Benzenum 12 CH. The homeopathic medicine in question, Benzenum, was able to reduce the mortality expected for LD50 3.0422 mL / kg of benzene, showing the Law of Similar, one of the pillars of Homeopathy. / Doutor

Submitted by Rosina Valeria Lanzellotti Mattiussi Teixeira (rosina.teixeira@unisantos.br) on 2017-08-05T13:12:51Z No. of bitstreams: 1 Luciano Braga de Oliveira.pdf: 2158750 bytes, checksum: 781582f0d9ba1728d24ccfd5b4927041 (MD5) / Made available in DSpace on 2017-08-05T13:12:51Z (GMT). No. of bitstreams: 1 Luciano Braga de Oliveira.pdf: 2158750 bytes, checksum: 781582f0d9ba1728d24ccfd5b4927041 (MD5) Previous issue date: 2017-03-29 / INTRODUCTION: The economic growth turned Brazil into one of the greatest agrochemicals consumers in the world. However, there were few studies that analyzed agricultural workers health exposure. OBJECTIVE: Evaluate the prevalence of cardiovascular symptoms on tomato rural workers (GE) exposed to agrochemicals in the Cuncas Valley, Barro ¿ CE. METHODS: A cross-sectional study questionnaire was applied to 50 tomato rural workers (GE), aged at least 18 years old, in their work place. A control group was selected from the not exposed population (GNE) paired by gender and age. It was used two questionnaires: a bio demographical, in order to analyze the schooling, income, marital status, residence type, medications and cardiovascular symptoms; and a protocol questionnaire about agrochemicals health effects to verify preparation steps, application, packaging destination, work clothes, use of Individual Protection Equipment (IPEs), perception and search for health services (hospitals or health basic units) in case of health alterations after agrochemicals application. It was applied a descriptive analysis, chi-square test, two proportion test and a logistic regression. The significant level was 5%. RESULTS: The exposed mean age was 41.42 (sd=10.50), and for the non-exposed group was 42.42 (sd=15.91). Ninety four percent was male, with some schooling. In the exposed group all tomato workers used agrochemicals, 66% not differ the toxicological products classification, only 22% read the packages. In relation to the agrochemicals, the same group, 94% used according to the recommended measures, 76% used daily, 98% used manual application and 78% avoid agrochemical overdose. Workers exposed to the agrochemicals presented more irritability (p<0.001), mental confusion (p=0.001), shortness of breath (p=0.003), sweating (p=0.008), dizziness (p=0.046), and headache (p=0.047). Rural workers exposed to agrochemicals had more chance to have a stomachache (RP=3.92, CI95%: 1.01 ¿ 15.22), chest pain (RP=5.33, CI95%: 1.68 ¿ 16.97), tachycardia (RP=4.48, CI95%: 1.34 ¿ 14.24), palpitation (RP=3.53, CI95%: 1.05 ¿ 11.86) and hypertension (RP=5.18, CI95%: 1.53 ¿ 17.99) when compared to the non-exposed group. In the exposed group the workers who did not give particular attention to clothes had more chance to developed hypertension (RP=5.70, CI95%: 1.01 ¿ 33.27) and cardiovascular disease (RP=5.40, CI95%: 1.01 ¿ 30.17). CONCLUSION: Exposure to agrochemicals affected the cardiovascular and gastric health system. / INTRODUÇÃO: O Brasil é um dos maiores consumidores de agrotóxico do mundo, devido ao crescimento econômico. No entanto, existem poucos estudos que avaliam os efeitos dos agrotóxicos nos trabalhadores rurais. OBJETIVO: Avaliar a prevalência dos sintomas cardiovasculares nos trabalhadores rurais da cultura do tomate expostos (GE) ao agrotóxico no vale de Cuncas, Barro ¿ CE. MÉTODO: Foi realizado um estudo de corte transversal através da aplicação de questionário no local de trabalho com todos os trabalhadores da cultura de tomate (50 trabalhadores), como critério de inclusão temos maiores de 18 anos idade. E um grupo controle a partir população não exposta (GNE) pareado por sexo e idade. Foram utilizados dois questionários: um biodemográfico cujas questões quanto ao sexo, idade, grau de escolaridade, renda familiar, situação conjugal, tipo de residência, medicamento e sintomas cardiovasculares. E outro questionário do protocolo sobre o efeito do agrotóxico na saúde, como os modos de preparo, aplicação e a destinação das embalagens, uso dos EPIs, percepção e busca aos serviços de saúde ¿ postos de saúde e/ou hospitais ¿ por alguma alteração após aplicação do agrotóxico. Foi realizada a análise descritiva, testes de Qui-quadrado e/ou exato de Fisher, de comparação entre duas porcentagens, e a regressão logística. O nível de significância foi de 5%. RESULTADOS: A população estudada tem uma idade média de 41,42 anos (DP ±10,50) para os expostos e 42,42 anos (DP ±15,91) para os não expostos. 94,0% é do sexo masculino, e com algum tipo de escolaridade. No grupo expostos todos utilizam o agrotóxico, 66,0% não diferenciam a classificação toxicológica dos produtos, 22,0% leem as embalagens. Possuem conhecimentos de manejo pois 94,0% sempre usa a quantidade recomendada, com uso diário em 76,0% do universo e 78,0% evitam a superdosagem e de aplicação manual para 98,0%. Em relação aos efeitos dos agrotóxicos apresentam maior irritabilidade (p=0,000), confusão mental (p=0,001), sudorese (p=0,008), tontura (p=0,046) e cefaleia (p=0,047). Os trabalhadores expostos ao agrotóxico apresentaram maior chance para dor no estômago (RP = 3,92, IC95%: 1,01 - 15,22), dor torácica (RP = 5,33; IC95%: 1,68-16,97), taquicardia (RP = 4,48, IC95% 1,34 - 14,24), palpitações (RP = 3,53, IC95%: 1,05 - 11,86) e hipertensão (RP = 5,18, IC95%: 1,53 - 17,99), quando comparado ao grupo não exposto. No grupo exposto que não deu atenção especial as roupas, os trabalhadores apresentaram mais chance de desenvolver hipertensão (RP = 5,70, IC95%: 1,01 - 33,27) e doença cardiovascular (RP = 5,40, IC95%: 1,01 - 30,17). CONCLUSÃO: A exposição aos agroquímicos afetou o sistema de saúde gástrico e cardiovascular.

Members of the legal system (e.g., experts, jurors, investigators) are often skeptical of the information provided by intoxicated witnesses given the negative stigma surrounding alcohol and memory. However, studies examining the relationship between alcohol and witness memory often find that alcohol has no effect on peoples’ recall or their ability to identify a previously seen face. While insightful, the validity of these findings has been questioned given the low-moderate blood alcohol concentration (BAC) levels tested in these predominantly laboratory-based studies, which may not be high enough to consistently expose the cognitive deficits alcohol is expected to create. The present study examined how elevated BAC levels affect witnesses’ recall. In addition, it examined how identification format (i.e., showup versus lineup) impacts witnesses’ identification decisions at elevated BAC levels. Bar patrons (N = 132) were asked to participate in a study examining the effects of alcohol on cognitive and motor functioning. Consenting patrons’ BAC levels were recorded and they were given instructions for their first motor task. Midway through this task a confederate intruder entered the room and caused a disturbance. Participants were then asked to recall the intrusion via a mock interview and identify the intruder from a lineup or showup in which she was pictured (target-present) or was not pictured (target-absent). This procedure yielded participants with BAC levels as high as .24%. Linear regressions showed that elevated BAC levels reduced both the quantity and quality of information provided by participants. Logistic regressions showed that alcohol had no effect on identification decisions, regardless of identification format or target presence. These data highlight the importance of testing witnesses’ memory across a broad BAC spectrum and suggest that the legal system may benefit from expert information on alcohol’s lack of effect on memory for faces, despite what jurors may believe.

<p>There is today much evidence for a positive relationship between alcohol and violence. There are however still many questions about the nature of the relationship. Somewhat simplified, the research on the link between alcohol and violence can be divided into four different lines of research, research focusing on: the effect of alcohol as a psychoactive substance, the drinking context, the personality of the drinker, and societal attitudes, expectations and values. The dissertation focuses on the last area, the importance of the cultural context. One influential theory within this field is the time-out theory formulated by MacAndrew and Edgerton in the late 1960s. Since drunken comportment varied between cultures and between different contexts within the same culture and changed over time, they suggested that the effects of alcohol on people’s behaviour was socially constructed. They suggest that many societies had a created a time-out situation for drunken behaviour that explained people’s behaviour while drunk.</p><p>The general aim for this dissertation is to study young Swedes’ attitudes, experiences and expectations around drunken behaviour, with a special focus on expectancies around alcohol as a cause and excuse for violence. Three different data sets have been used. The first study is based on 4 focus-group interviews with Swedish football fans during the European football championship in Holland in 2000. The second material is eight focus-group interviews involving 47 students aged 18-20 living in Stockholm. The last material is a nationally representative survey of young adults, 16-25 years old. One part of the survey consisted of 4 vignettes which we used to elicit cultural norms around drunken behaviour.</p><p>The findings suggest that young Swedes believe that alcohol can be used as a means to accomplish a pleasurable state of mind, and that alcohol could be used as a means to transgression – since alcohol reduce inhibitions it could be used to put them in a less controlled mode. The rationale for those changes was often described in terms of the psychoactive effect of alcohol. However, it was also shown that the context was important. When the situation demanded alcohol the most, their expectations together with the situation almost turned water into beer. It was also shown that there was a norm which said that one should not use alcohol as an excuse, but on the other hand, the participants said that they used alcohol as an excuse and that they thought that it was accepted. Alcohol could work as an excuse since alcohol made the aggressor look less deviant and the acts less severe. The vignette studies indicated that an aggressor who was drunk when he committed a violent act was seen as less blameworthy than a sober or less drunk aggressor. However, this applied only under certain circumstances: alcohol seemed to be a better excuse if the victim is drunk as well and the act is relatively severe.</p><p>Taken together, the studies suggest that the Swedish drinking culture provides people with a drunken excuse, which helps young people to expand the room for possible action.</p>