Th. Méd.--Nancy 1, 1983. N°: 90.

At present, there is a high number of epidemiologic studies dealing with children´s injuries and intoxication but children´s view seemed to be interesting to be focused. The aim of this Diploma work has been to provide readers with a children´s view of injuries and intoxication, their perception of risks and the knowledge of prevention.

Functional constipation (FC) is a major gastrointestional (GI) disorder which affects about 14% population worldwide. However, due to efficacy and safety concerns, more than 50% FC patients are not completely satisfied with current conventional therapies, thus alternative therapies are needed. A substantial part of FC patients have symptom of slow colonic motility, while therapy targeting a single pathway cannot benefit all of them. In this thesis, we searched for novel FC therapeutics from two distinct sources, both of which can improve colonic motility significantly: (1) MaZiRenWan (MZRW), an herb formula from Traditional Chinese Medicine (TCM); and (2) Spexin (SPX), a newly identified neuropeptide that is deregulated in FC. On the basis of efficacy validation for MZRW by randomized, placebo-controlled clinical studies, we investigated the bioactive compounds and pharmacological actions of MZRW. Firstly, a machine-learning based method, namely MOST, was developed to relate bioactive compounds with their mechanism-of-action targets. MOST demonstrated good performance in 7-fold cross-validation (over 87% accuracy) and temporal validation (over 76% accuracy). In the case laxative effect, MOST predicted that acetylcholinesterase (ACHE) was the mechanism-of-action target of aloe-emodin; in vivo studies validated this prediction. Secondly, we analyzed the bioactive compounds and mechanism-of-actions of MZRW with combination of UPLC-QTOF-MS/MS, clustering analysis, organ bath, and MOST approaches. 97 compounds were identified in MZRW extract, and 35 of them can be found in plasma and feces samples of rats with oral administration of MZRW. Chemical space analysis suggested that these compounds can be classified into component groups, while the corresponding pharmacology can be studied with representative compounds. Emodin, amygdalin, albiflorin, honokiol, and naringin were shown to induce spontaneous contractions of rat colonic smooth muscle in vitro. Biological targets in ACh-, estrogen-, prostaglandin-, cannabinoid-, and purine signaling pathways are able to explain the prokinetic effects of representative compounds and component groups. Pharmacological actions of MZRW are mixture of five classic paradigms. Thirdly, the latest results of three-armed, randomized and controlled clinical study showed that MZRW demonstrated comparable efficacy with the first line drug Senna, the first line drug for constipation in HK, during treatment period, both were better than placebo; and the efficacy was more sustainable in follow-up period when comparing that of Senna and placebo. These data suggested the unique pharmacological profile of MZRW for FC. With pharmacometabolomic analysis, we found that change of oleamide is negatively correlated (pearson r = -0.59, p<0.001) with improvement of Complete Spontaneous Bowel Movement (CSBM) in MZRW group, but not in Senna or placebo group. Oleamide is up-regulated in FC patients compared with healthy controls, and MZRW can significantly reduce oleamide in FC patients (n=30), healthy human volunteers (n=23), and in normal mice (n=12) serum, ileum, and colon. The regulation of oleamide by MZRW is possibly via augmenting FAAH-mediated degradation. Lastly, we investigated the possibility to use SPX, the newly identified, FC-associated neuropeptide to change GI motility. The deregulation of SPX has been found in several disorders including FC, however, the metabolic instability of SPX prevent it to be directly used in clinical practices. Our investigation through combination of molecular dynamics (MD) simulations and NMR analysis suggested a β-turn-helix-β-turn (βαβ) conformation for human spexin (hSPX) adopts in solution. Consistent with this conformation, cyclic analogues of hSPX with a disulfide bond between residue 1 and 13, LH101 (CWTPQAMLYLKGCQ-NH2), activated both GalR2 (EC50=1.19 μM) and GalR3 (EC50=1.56 μM) with potency comparable to wild type, and that the acetylation at the N-terminal, LH101(Ac) raises the potency EC50=0.38 μM on GalR2 and EC50=0.39 μM on GalR3. The serum half lives of LH101 (t1/2=355.7 min) and LH101(Ac) (t1/2=1973.7 min) were significantly longer than the wild type (t1/2=66.5 min), and LH101(Ac) induces the contractions of mice intestinal segment in vitro and attenuates the oleamide-induced slow GI motility in vivo. Collectively, our studies in MZRW suggested that estrogen and oleamide signaling pathways are potential new targets to develop novel therapeutics for FC, while lead compounds targeting these pathways could be found from MZRW. The final study suggested CSAs have potential to be developed as new FC therapy by targeting the galanin receptor associated pathway.

Ethylene glycol intoxication, suicidal as well as accidental, belongs to serious, immediately life-threatening poisonings, which can however be cured even in the most severe cases (provided early recognition and correct treatment), including the restoration of renal function to the original state. Ethylene glycol is most notably present in anti-freeze cooling liquids for vehicles (such as Fridex). Consumption of 100-150 ml of such a solution is considered a lethal dose in humans. follows Oral ingestion is followed by rapid absorption. Metabolic decomposition takes place predominantly in the liver by way of alcohol dehydrogenase, to glycoaldehyde, which is further metabolised to glycolic acid and oxalic acid. The clinical aspect is dominated by acute renal failure which is caused by acute tubular necrosis. Toxicological examination including an assessment of ethylene glycol levels in both blood and urine, with prognostic relevance, is indispensable to diagnostics of the poisoning as well as from the standpoint of differential diagnostics. Therapeutic measures include gastric lavage within one hour of ingestion and administration of activated charcoal. Administration of ethanol and fomepizole, compounds that bind alcohol dehydrogenase and thus prevent the conversion of ethylene glycol to its toxic metabolites, is considered valid causal treatment with simultaneous early institution of hemodialysis (even in cases of hitherto intact renal function). As fomepizole is currently not available in the Czech republic, ethanol remains the only antidote. Therapy further includes correction of metabolic acidosis by way of bicarbonates, and intravenous application of thiamine and pyridoxine. Therapy of such a grave condition must entail infirmary care provided by professional nurses as a necessary complement. The nurse serves their function in securing the patient's airways, connecting the patient to mechanical ventilation, monitoring physiological functions, assistance with invasive entry, as well as conducting sample extractions, assuring proper hygiene, the prevention of decubitus ulcers etc. It has been the aim of an extensive effort during my analysis of this topic to collate an up-to-date summary of practical knowledge on ethylene glycol intoxication, as well as subsequent therapeutic options for such patients, based on collected information and available source material. This final thesis, entitled "Approach and Options for Nurses in Therapy of Ethylene Glycol-intoxicated Patients" has been created relying on a body of purely theoretical Czech and foreign sources. To attain awareness of the current state of medical sciences described on the following pages, many professional and scientific publications, books as well as journals and websites of registered professional societies had to be studied. The aim of a detailed inspection of such an extensive body of data has been to provide relevant findings based on the facts determined. The accumulated information is further specified in particular sections. The first deal with intoxication, elimination and first aid in the pre-hospitalization phase from a broader perspective. Without these elementary notes the thesis as a whole would lack in conclusiveness. From this section the thesis fluidly continues with ethylene glycol intoxication itself, its treatment and all the way to the role of the nurse including particular therapeutic measures. These sections contain specific recommendations issuing from news and cutting-edge research on ethylene glycol poisonings.

The association between intoxication by hazardous chemicals and selected parameters response of the Integrated Rescue System is currently a frequently discussed theme. This connection is especially observed where the main source of carbon monoxide poisoning. Fire and Rescue Service of the Czech Republic in cooperation with the Integrated Rescue System units solves a wide range of events every year just with the leakage of carbon monoxide. This gas was, and today still is the cause of much intoxication, especially when using Karma for water heating. That is the reason why this thesis focuses precisely on the investigation of selected parameters response of the Fire and Rescue Service of the capital City of Prague upon the carbon monoxide occurrence. Important factors influencing the progress of the intervention is i.a., knowledge of the toxic effects of this gas and its effects on the human body, but also adequate quantity and quality of the detection devices and protective equipment. This diploma thesis deals with the investigation of selected parameters mentioned above emergency interventions, be subsequently treated by in the period from 2010 to 2014 under the Fire and Rescue Service of the capital City of Prague. The theoretical part describes the hazardous chemical substance (carbon monoxide) in terms of chemical, physical, biological, and also its use. The important part is the detailed description of the intoxication of carbon monoxide in the organism, the degradation of the organism, consequences of poisoning and medical procedures. Further have been also described respiratory protective devices, which are focused on the protective filters. When processing the diploma thesis is also found all events with the release of carbon monoxide in the capital City of Prague territory. These data are based on the statistical monitoring of events that leads and processes Fire and Rescue Service of the capital City of Prague. From statistic of interventions are subsequently searched data on the number of killed, wounded and rescued persons who are within the statistics registered. As comparative parameters are selected data on average daily temperatures and average daily pressures in the capital City of Prague territory. These data are for the period provided by the Czech Hydrometeorological Institute, Prague subdivision. The diploma thesis is determined and verified hypotheses of influence of the average daily temperature on the frequency of interventions with the presence of carbon monoxide in the capital City of Prague territory in the monitored period, average daily pressures influence on the frequency of interventions with the presence of carbon monoxide in the capital City of Prague territory and affect of the average daily temperature on the average daily pressures. The gained information is comprehensively and detailed processed into tables. The events in tables are divided by years, months. Afterwards it provides a general overview of emergency interventions in the monitored period. The processed data are then statistically examined and evaluated. In the first part is determined statistical unit for the period of five years. The data are also tabulated together with the average temperature and the average pressure and then suitably scaled. Then calculation of the general moments of the first order, standard deviations and correlation analysis follows. The results are compared with prescribed intervals. Based on a comparison of the results with the prescribed intervals is evaluated that the number of events does not correlate with the temperature, so the number of events with a temperature not connected, the number of events is positively correlated with the pressure, which means that the number of events related to the pressure. The temperature correlates positively with the pressure, i.e., these two parameters together, purview within performed examination, related.

The aim of this diploma thesis was to process an overview of previously known knowledge about acute mushroom poisonings. Thesis draws mainly from foreign literature. Provides basic information about mushrooms, their toxins and syndromes that cause. Beside the general information, one part of the thesis is devoted to the cases and studies from around the world. They describe individual clinical cases of mushroom poisoning or deal with their epidemiological situation mostly between the years 2001 - 2016. Obtained information is processed into overview tables. Thesis is particularly focused on the situation of macromycete poisonings in the Czech Republic and contains data from specialised facilities. The most intoxications occurs after ingestion of the edible fungi species. The most common intoxications by mushrooms containing toxins are after ingestion A. phalloides, A. pantherina and Psilocybe. The most frequent reported symptoms are gastrointestinal. According to the severity, mushroom poisonings are classified as less dangerous with onset of symptoms within 6 hours and life-threatening with the onset of symptoms after more than 6 hours. Mushroom poisonings should be considered in the differential diagnosis of gastrointestinal problems. Key words: macromycetes, mushroom poisonings, mushroom...

Analgesics represent a large group of medicines which is used for suppresing subjectively perceived pain. Analgesics can be divided into two large groups, opioids and non-opioids. Some of the non-opioids can be used as anti-inflammatory and/or antipyretics as well. All non-opioids influence metabolism of prostaglandins. Diverse group of non-opioid analgesics is available in Czech pharmacies as prescription medicines or for sale over the counter. The aim of this work is mainly to assess the toxicity of over-the-counter analgesics and to find out the frequency of fatal intoxications caused by these analgesics in the Czech Republic and abroad. A list of peroral over-the-counter analgesics was created. A partial analysis of data from medical judicial departments of regional hospitals in the Czech Republic was performed in order to obtain total number of deaths caused by overdosing with these drugs. Using ÚZIS the number of deaths was extracted from information system Deceased. These logged deaths were caused only by acute intoxication with analgesics and were chosen on basis of precisely defined combinations of diagnostic codes (MKN10). Results were then expanded by similar enumeration from the National register of hospitalized, by which we specified the amount of intoxications where patients survived. Overall case report was evaluated from processed information. The number of deaths caused by analgesics and commonly misused addictive substances were compared by which the second hypothesis was clarified. The data was obtained from Annual reports about substance misuse and 6 years were compared in total. Identified risk of analgesic in Czech Republic was compared with registered cases of overdosing in world. Data used for comparing were gained from analysis of world literature. During the years 2006 ? 2011, 53 deaths and 2024 hospitalizations in the Czech Republic were caused by acute intoxication as a result of overdosing with mentioned medication. Our first hypotesis can be confirmed on the basis of these numbers, and therefor it can be said that over-the-counter medicines used for suppressing pain can cause death. On the basis of analysis of world literature a certain risk is seen in fact that these analgesics ? mainly paracetamol ? are often linked with suicides. For instance in United Kingdom thousands of cases of self-harm are caused by overdosing with paracetamol. In USA 16 500 deaths are thought to be caused by NSAIDS and 1600 acute liver failure incidents are caused by overdosing with paracetamol annualy. Illegal drugs caused 253 intoxications during the years 2006 -2011 compared to 53 cases of deaths caused by overdosing by analgesics. Annual reports about substance misuse report that deaths caused by illegal drugs are more common than deaths caused by over-the-counter analgesics in the Czech Republic. There remains a question: What percentage of analgesics intoxications, where patient survived or not, is caused only by over-the-counter analgesics without any other cause.

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-04-08Bitstream added on 2014-06-13T20:41:31Z : No. of bitstreams: 1 chaves_dp_dr_jabo.pdf: 730036 bytes, checksum: 6a829df01b57aa4cc11a6f8e439fe13e (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / lpomoea asarifolia é uma planta tóxica da familia Convolvulaceae, amplamente distribuida no Brasil, especialmente nas regides Norte e Nordeste. Para compreender os mecanismos fisiopatológicos da intoxicagao, 25 ovinos foram distribuidos em cinco grupos que receberam 25% (Cl), 50% (G2), 75% (G3) e 100% (G4) de inclusäo da planta na alimentação. 0 quinto grupo (G5) tambêm recebeu 100%, mas, diferentemente do G4, o fornecimento foi interrompido após a manifestacäo clinica da intoxicação. Realizou-se exame fisico durante 30 dias, iniciando imediatamente antes do fornecimento de I. asarifolia para os grupos G1 a G4 e depois da intoxicacão para o G5. A cada cinco dias foram colhidas amostras de sangue para exames hematológicos e bioquimicos. Dois animais de cada grupo foram submetidos necropsia, colhendo-se amostras de figado, rim e encêfalo para exame histopatológico. Constatou-se mortalidade elevada entre os grupos Cl a G4 e todos os animais do G5 se recuperaram entre três a sete dias após a suspensäo do consumo da planta. Os sinais clinicos iniciaram a partir do segundo dia da ingestão, caracterizando-se por ranger de dentes, hiperemia de membrana mucosa conjuntival, excitabilidade, tremor, desequilibrio e queda. 0 hemograma mostrou variageies discretas. 0 perfil bioquimico indicou que as atividades das enzimas hepaticas nao foram influenciadas pelas lesbes de figado, constatadas ao exame histológico. 0 proteinograma revelou ate 31 proteinas, corn pesos moleculares entre 19.160 e 250.500 Da, corn destaque para os valores de transferrina e de al-glicoproteina acida. Constatou-se degeneracäo hidrópica de hepatócitos, necrose tubular renal discreta, porêm difusa e vacuolizacao intracitoplasmatica de neurônios. A intoxicacão de ovinos por I. asarifolia foi dependente do percentual de sua inclusäo na dieta. / Ipomoea asarifolia is a toxic plant belonged to Convolvulaceae family widespread in Brazil, especially in the north and northeast regions. To understand the intoxication physiopathologic mechanisms, 25 sheep were distributed in 5 groups where they received 25% (G1), 50% (G2), 75% (G3) and 100% (G4) of the plant as source of food. The fifth group (G5) received also 100% of!. asarifolia but, differently of the G4 the intake was interrupted just after a clinic intoxication manifestation. Physical exams were done through 30 days, starting immediately before the I. asarifolia from G1 to G4 and after intoxication to G5. In each five days blood samples were collected for hematologic and biochemical exams. Two animals from each group were submitted to necropsy collecting liver, kidney, and brain samples to histopathologic exams. A high mortality was observed among the G1 to G4 and all G5 animals recovered themselves from three to seven days after /. asarifolia ingestion suppression. The clinic signs started from the second day of ingestion, characterized by gnash, conjunctival mucous membrane hyperemia, excitability, shaking, lost of equilibrium, and falling. Hemogram showed discrete variations. The biochemical profile indicated that the hepatic enzymes activities were not influenced by the liver damage presented in the histological exam. The proteinogram revealed up to 31 proteins, molecular weigh from 19,160 to 250,500 Da, highlighting the transferrin and al-acid glycoprotein levels. Hepatocyte hydropic degeneration was observed, discrete renal tubular necrosis and neuron intracitoplasmatic vacuolization. The sheep intoxication by!. asarifolia was dependent of its percentage inclusion in the diet.

Made available in DSpace on 2014-06-11T19:31:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-09-05Bitstream added on 2014-06-13T20:47:25Z : No. of bitstreams: 1 camargo_cp_dr_jabo.pdf: 4012168 bytes, checksum: 9085b257725b5e717174aa9588d8cb98 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / 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. / 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.

Orientador: Luiz Edvaldo Pezzato / Banca: Wilson Massamitu Furuya / Banca: Fabiana Pilarski / Resumo: O farelo de pinhão manso (Jatropha curcas) é um ingrediente protéico que se apresenta como possível substituto alternativo do farelo de soja nas rações. Entretanto, faltam informações a respeito de seu valor nutritivo e da ação dos fatores antinutricionais presentes, para peixes. Por 90 dias foi realizado experimento para avaliar o efeito da inclusão do farelo de pinhão manso (FPM) em dietas para tilápia do Nilo. Foram utilizados 240 peixes com 13,82 ± 0,39 g de peso médio inicial e foram distribuídos em 30 aquários de 250L num delineamento inteiramente casualizado. Os peixes foram alimentados com dietas (isoprotéicas = 32,00% PB, isoenergéticas = 4000 kcal ED/kg e isofibrosas = 8,7% de FB), contendo níveis crescentes de inclusão de FPM (0,0; 1,0; 2,0; 4,0; 8,0 e 16,0%). A composição química do FPM, o consumo de ração (CR), ganho de peso (GP), conversão alimentar (CA), porcentagem de mortalidade (MORT%) e índice hepatossomático (IHS) foram avaliados. Aos 45 e 90 dias todos os peixes foram anestesiados e pesados. Um peixe por aquário foi sacrificado para determinar a proteína bruta (PB), extrato etéreo (EE), umidade (UM) e cinzas das carcaças. Os valores de UM, cinzas e EE diminuíram com a inclusão de FPM na ração (P<0,05). Peixes alimentados com 2, 4 e 8% de FPM apresentaram maior teor de PB. Esta diferença foi provavelmente devido ao menor teor de EE desses peixes. Observou-se efeito quadrático negativo para as variáveis GP e CR e efeito quadrático positivo para a CA. A equação de regressão demonstrou que valores acima de 5,55% de inclusão de farelo de pinhão manso são significativamente prejudiciais para o desenvolvimento dos peixes. O IHS apresentou efeito linear negativo de acordo com o aumento do nível de FPM na dieta. Os peixes do tratamento 16%FPM apresentaram menor tempo de vida e 100% de mortalidade, indicando a alta toxicidade do FPM... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Jatropha curcas meal is a vegetable protein-rich ingredient which could be used in animal diets as a soybean meal substitute. Otherwise, information is lacking regarding to its nutritional value and the effect of antinutritional factors for fish. A 90-day feeding trial was performed to evaluate the effect of jatropha meal (JM) inclusion in diets for Nile tilapia. Two hundred and forty fish with 13.82 ± 0.39g mean initial weight were randomly assigned to 30 250l-aquaria in a completely randomized design. Fish were fed diets (isonitrogenous = 32.00% DP, isoenergetic = 4000 kcal GE/kg diet and same fiber level = 8.7% CF) containing graded JM levels (0.0, 1.0, 2.0, 4.0, 8.0 and 16.0%). Jatropha meal chemical composition, feed intake (FI), weight gain (WG), feed conversion ratio (FCR), mortality and hepatosomatic index (HSI) were evaluated. At 45 and 90 days all fish were anesthetized and weighed. One fish per aquarium was killed to determine dry matter (DM), ash, crude protein (CP) and ether extract (EE) content of fish carcass. Ash, DM and EE content reduced according to JM inclusion levels (P<0.05). Fish fed 2, 4 and 8% JM had higher CP content. This difference was probably due to the lower EE content of these fish. A negative quadratic effect was observed for WG and FI while positive quadratic effect was observed for FCR. The regression equation demonstrated that inclusion JM levels above 5.55% depressed fish growth. HSI showed negative linear effect according to increasing JM level in the diet. Fish fed 16% JM showed the lowest life span and completely died before the end of the experiment, indicating the high toxicity of JM. Tilapia fed JM showed anorexia signs, erratic swimming... (Complete abstract click electronic access below) / Mestre