Techn. University, Diss., 2005--Darmstadt.

Thesis (M.Sc. (Environmental Biology))--Mahidol University, 1982.

Thesis (Ph.D.) - University of Queensland, 2005. / Includes bibliography.

Orientador: Angelo Zanaga Trape / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-04T03:10:39Z (GMT). No. of bitstreams: 1 Silva_AdaelsonAlves_D.pdf: 4937372 bytes, checksum: 6f3ac3a0b57da499f879075123c2041c (MD5) Previous issue date: 2004 / Resumo: A intoxicação aguda por agrotóxicos inibidores das colinesterases é causa substancial de morbidade e mortalidade em todo o mundo. No Brasil, como nos demais países, os efeitos tardios à saúde humana em decorrência de intoxicação aguda por agrotóxicos continuam não muito bem conhecidos, constituindo um desafio para os pesquisadores. Este trabalho teve como objetivo avaliar a saúde de 33 indivíduos, 20 homens e 13 mulheres, que softeram intoxicação aguda por agrotóxicos inibidores das colinesterases, entre janeiro de 1994 e dezembro de 2000, notificados no Centro de Controle de Intoxicações de Maringá e que necessitaram de tratamento hospitalar. Para a avaliação compareceram 36 indivíduos, que consentiram participar da pesquisa. Foram excluídos do estudo três deles: dois por serem portadores de doença psiquiátrica, anterior ao episódio de intoxicação, e uma criança, portadora de distúrbio neurológico, também anterior à intoxicação. Quanto ao tempo decorrido após o episódio de intoxicação, 19 (57,6 %) tinham 6 anos ou mais, sendo que 8 (24,2%) situavam-se na faixa entre 9 e 10 anos pós-intoxicação. A tentativa de suicídio foi a circunstância da intoxicação mais &eqüente no grupo estudado (60,6% ). Em relação à profissão, 33,3% eram agricultores. A faixa etária era predominantemente de jovens e aduhos (66,7%), com idade entre 16 e 40 anos. Os inseticidas organofosforados foram responsáveis por 20 intoxicações (60,6%) e os inseticidas carbamatos por 13 intoxicações (39,7%). A necessidade de internamento em UTI (42,4%) caracterirou a gravidade das intoxicações. Quanto aos sinais e sintomas referidos pelos indivíduos no momento da investigação, encontrou-se cefaléia (33,3%), insônia (33,3%), epigastralgia (27,3%), irritabilidade (18,9%) e fraqueza muscular (15,1%). A incidência de hipertensão arterial (42,4%) foi maior no grupo investigado que na população geral A av~li:lção laboratorial mostrou que a função renal estava normal em todos os indivíduos e anormalidades bioquímicas hepáticas, avaJi9das pelas dosagens séricas da alanino aminotransferase (AST), aspartato aminotransferase (ALT) e gama glutamil transferase (GAMA GT), estavam presentes em 30,3% dos indivíduos do grupo: três pacientes em duas e um nas três en7.ima~. O exame neurológico estava normal e quatro indivíduos apresentaram aherações eletroencefalográficas. As dosagens das colinesterases séricas apresentaram pequenas alterações. Diante dos resuhados, concluiu-se que o protocolo utilizado não foi capaz de evidenciar aherações significativas na saúde dos pacientes examinados, sendo que as anormalidades bioquímicas hepáticas e a alta incidência de hipertensão arterial encontradas apontam a necessidade de estudo complementar ,para o estabelecimento do nexo causal / Abstract: Acute intoxication by cholinesterase-mJnõiting pesticide causes substantial morbidity and mortality worldwide. In Brazil and other countries, the Jate efIects to human health due to acute intoxication by pesticides continue not well known, which is a challenge to researchers. The current writing aimed at to evaluate the heahh conditions of 33 individuaIs, 20 men and 13 women, that were exposed to acute intoxication by cholinesterase-inlnõiting pesticide within January 1994 and December 2000, notified at the Intoxication Control Centre from Maringá and that needed hospital treatment. For the study, 36 individuaIs agreed to take part ofthe research. Three ofthem were excluded: two by having psychiatric diseases prior to intoxication and a child with neurologicaI disturb aIso prior to intoxication. As for the time after the intoxication episode, 19 (57,6%) had been intoxicated 6 years before the research, 8 (24,2%) had intoxicated between 9 and 10 years before. Suicide attempt was the main intoxication cause within the group studied (60,6%). As for the profession, 33,3% were agricuhurists. The main age group was young, with ages from 16 to 40 years (66,7%). Organophosphate pesticides caused 20 intoxications (60,6%), and carbamate pesticides caused 13 intoxications (39,7%). The necessity ofICU internment (42,4%) demonstrated the gravity of intoxications. As for the signaIs and symptoms related by individuaIs at the investigation, could have been found headaches (33,3%), insomnia (33,3%), stomach-aches (27,3%), irritability (18,9%) and muscle weakness (15,1%). The incidence ofhyper blood pressure (42,4%) was greater at the study group than at the ordinary population. LaboratoriaI investigation showed that renal function was normal within all individuaIs, and hepatic function, assessed by the blood dosage of aIanine aminotransferase (AST),aspartate aminotransferase (ALT) and gama glutamil transferase (GAMA GT), modified in 30,3% of individuaIs ITomthe group: three patients in two and one in the three enzymes. The neurologicaI exam was normal and four individuaIs presented electroencephalographic modifications. The dosages of blood cholinesterase showed little aherations. From the resuhs of the research, it can be concluded that the protocol applied could not evidence significant changes on the heaIth of patients examined. The hepatic biochemicaI abnormalities and the high incidence of hyper blood pressure suggest the necessity of complimentary studies in order to establish causal nexus / Doutorado / Saude Coletiva / Doutor em Saude Coletiva

Inledning: År 2030 uppskattas det vara ungefär 230 000 stycken människor i Sverige somhar drabbats av någon typ av demenssjukdom. Sjukdomens stadier delas in i begynnande,mild, måttlig och svår demens. Där första symtomen i den begynnande fasen brukar vara attden drabbade inte kommer ihåg vart den lagt sina saker. I den svåra fasen av sjukdomen ärpatienten förmodligen beroende av dygnet runt vård, patienten brukar även ha svårt attprata, enstaka ord eller meningar brukar upprepas. Beteendemässiga och psykiska symtom(BPSD) hos demenssjuka är symtom som kan orsaka lidande hos patienten och dessanhöriga. Symtomen delas in i fyra undergrupper affektiva, psykossymtom, hyperaktivitetoch apati. Riskfaktorn med högst evidens är Apolipoprotein E (ApoE), ApoEε4-allelen.Riskfaktorer med lägre evidensgrad är t.ex. låg utbildning och släktskap. Sjukdomen orsakas av att nervcellerna i hjärnan dör, framförallt i delen av hjärnan därminnet sitter. En röntgen av hjärnan visar onormala proteininlagringar, amyloida plack.Amyloidhypotesen påstår att det blir en överproduktion av amyloid-beta proteinet vilken trosvara den patologiska händelsen vid Alzheimers sjukdom. Tauproteinet hyperfosfyleras till enisoform som är tre gånger större än i en frisk hjärna, om överproduktion av tau på specifikaställen eller hela hjärnan orsakar sjukdomen har forskarna inte kommit fram till ännu. Mildtill måttlig Alzheimers sjukdom behandlas med acetylkolinesterashämmarna donepezil,rivastagmin och galantamin. Svår Alzheimers sjukdom behandlas med en NMDAreceptoragonist,memantin. Syfte: Att undersöka om acetylkolinesterashämmare eller neuroleptika fungerar bäst vidsymtom som uppkommer vid BPSD, samt undersöka vilka biverkningar som är vanligast. Metod: PubMed har använts för att hitta studier som stämmer in på inklusionskriterierna.Studier som exkluderas är de som undersökt fel substans, fel indikation eller fel preparat t.ex.omega-3. Resultat: De vanligaste biverkningarna som rapporterats hos acetylkolinesterashämmarnaär bland annat illamående och kräkningar. Av neuroleptika preparaten verkar det varasömnighet som är den mest rapporterade biverkningen. Studierna som undersökteneuroleptika kom fram till ungefär samma sak, att preparaten kan förbättra symtomen. Av destudier som undersökte acetylkolinesterashämmarna var det tre studier som drog slutsatsenatt de kan ha effekt. En studie säger att det inte sågs någon skillnad mellan donepezil ochplacebo vid dessa typer av symtom. Diskussion: Då de olika studierna som använts i arbetet har undersökt olika effektmått hardet varit svårt att göra en rättvis bedömning om läkemedlen fungerar eller ej. Då i de flestafall bara gått och jämföra ett effektmått från studierna. Hade jag bestämt vilka effektmåttsom fick finnas i varje studie redan från början och sedan gjort en exkludering utifrån det,hade det varit enklare att jämföra studierna och därefter kommit fram till en bra slutsats. Viden jämförelse mellan de olika substanserna ur neuroleptikagruppen, är sömnighet denvanligaste biverkningen i tre av fyra grupper. Viktökning är också en av de vanligastebiverkningarna i två av grupperna där ungefär 32% drabbades av just denna biverkning.Varför patienterna ökat i vikt framgår inte i studierna. Slutsats: Acetylkolinesterashämmare och neuroleptika kan ha effekt vid symtom somuppkommer vid BPSD. Acetylkolinesterashämmarna bör provas i första hand om intebehandlingen redan är insatt.

Master of Science / Department of Biology / Brett K. Sandercock / Monitoring programs indicate that numerous shorebird populations are subject to on-going declines. The U.S. Shorebird Conservation Plan lists twenty-seven shorebird species as species of high concern and seven as highly imperiled, including the Buff-breasted Sandpiper (Tryngites subruficollis). One hypothesis for ongoing population declines is exposure to toxic chemicals and pollutants. The purpose of this project was to characterize plasma cholinesterases (ChEs) of migratory shorebirds and address potential exposure to organophosphorus (OP) and carbamate (CB) pesticides. Consumption or contact with these pesticides can cause mortality and a variety of sub-lethal effects. Buff-breasted Sandpipers and other upland shorebirds are particularly likely to encounter agrochemicals due to their habitat use at the non-breeding grounds. I sampled migratory shorebirds over three seasons, during north- and southbound migration in 2006 and 2007 in Texas, Kansas, and Nebraska and during the non-breeding season in 2007 in Argentina, Uruguay, and Paraguay. I collected blood samples and footwashings from reference sites, where OP and CB pesticides were not used, and agricultural sites, where these two insecticides were recommended for control of crop pests. I assessed several variables known to affect plasma ChE activity including body size, date of capture, time of capture, condition, sex, and region. Small-bodied species had higher levels of ChE activity in plasma than large-bodied species. Plasma ChE activities varied with date of capture in 3 of 5 species sampled in North America. Sex differences were significant in 1 of 4 species tested. Plasma acetylcholinesterase (AChE) activity was higher among White-rumped Sandpipers sampled in North America but there was no difference between regions among Buff-breasted Sandpipers. Time of capture and individual condition did not affect plasma ChE activity. Estimates of exposure to ChE inhibitors were addressed in five species. Plasma AChE and butyrylcholinesterase (BChE) activities of Buff-breasted Sandpipers were lower at agricultural sites in South America but BChE activity was higher at agricultural sites in North America. There were no differences between sites in four other species tested. A meta-analysis across all species indicated that in 4 of 6 comparisons habitat type had a negative effect on AChE activity consistent with exposure to ChE inhibitors but there was a regional positive effect of agricultural habitat on BChE activity in North America. Comparison of body mass between sites suggested that use of habitats with potential pesticide application did not affect mass gain. Project results suggest that 1 of 5 shorebird species tested was exposed to ChE-inhibiting pesticides at the non-breeding grounds and future monitoring is necessary to assess potential effects at the population level. This study highlights the importance of complete sampling and addressing variability in plasma ChEs before making estimates of exposure to OP and CB pesticides. It provides the first estimates of migratory shorebird exposure to OP and CB pesticides, a potential conservation issue. Future research should include continued monitoring of Buff-breasted Sandpiper ChE levels and habitat use. Other sources of anthropogenic declines such as habitat loss and illegal hunting should be investigated for species that did not show evidence of exposure.

La prise en charge de la démence est un défi pour les cliniciens tant ces patients constituent une population hétérogène. Dans le cadre de cette prise en charge, l’intérêt des antidémentiels (anticholinestérasiques et mémantine) est débattue : l’efficacité clinique semble discutable et les effets indésirables non négligeables. En 2010, des recommandations de bonnes pratiques ont laissé libre choix aux médecins de prescrire ou non ces médicaments. Depuis des questions restent en suspens : 1/ quelle est l’évolution des taux de prescription de ces médicaments depuis ces recommandations, en d’autres termes comment l’expertise clinique des médecins, un des piliers du tryptique de l’evidence based medicine, s’est-elle exprimée ? 2/ quels sont les facteurs qui restent associés aujourd’hui au fait de prescrire ou non ces médicaments ? et 3/ y a-t-il une sur-hospitalisation liée à leurs effets indésirables ?La question de la surmédicalisation est au cœur de notre problématique de thèse. Dans ce travail, nous avons répondu à ces 3 questions posées qui ont constitué nos 3 objectifs. Nous avons pu montrer que les médecins semblaient de moins en moins confiants vis-à-vis des antidémentiels avec une diminution de leur prescription depuis 2010 et des conséquences importantes en termes de coûts évités. Lorsqu’ils continuaient d’être prescrits, ces traitements l’étaient essentiellement chez les patients les plus jeunes ou en meilleur état de santé. Enfin, les anticholinestérasiques, essentiellement la rivastigmine, augmentaient le risque d’hospitalisation via des effets indésirables cardiaques et digestifs. Nos résultats plaident en défaveur de la prescription d’antidémentiels tant du point de vue de la morbidité que des dépenses de santé. La question du point de vue du patient reste posée. / Patients with dementia raise therapeutic challenges, as they constitute a heterogeneous population. As part of this management, the interest of antidementia drugs (cholinesterase inhibitors and memantine) is debated: the clinical efficacy seems questionable and the adverse effects appear to be significant. The 2010 recommendations gave to cliniciens the choice to prescribe or not these drugs. Since questions remain unanswered: 1 / what is the evolution of prescription rates of these drugs since these recommendations, in other words how the clinical expertise of cliniciens, one of the pillars the evidence based medicine, is expressed? 2 / what are the factors that remain today associated with prescribing these drugs or not? and 3 / Is there over-hospitalization related to their side effects?The question of medical overuse is a central point of our thesis problem. In this work, we answered these 3 questions which constituted our 3 objectives. We were able to show that cliniciens seemed less and less confident about antidementia drugs with a decrease in their prescription since 2010 and significant consequences in terms of avoided costs. When they continued to be prescribed, these treatments were mainly used in the youngest or most healthy patients. Finally, cholinesterase inhibitors, mainly rivastigmine, increased the risk of hospitalization via cardiac and digestive side effects. Our results argue against the prescription of antidementia drugs both from the point of view of morbidity and health expenditures. The question from the patient's point of view remains.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tereza Kalinová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Mentor: Assoc. Prof. Jana Hroudová, Pharm.D., Ph.D. Title of diploma thesis: Effect of cholinesterase inhibitors on monoaminergic system and energy metabolism Cholinesterase (ChE) inhibitors play an essential role in the treatment of Alzheimer's disease (AD). They effect positively cognitive, functional and behavior symptoms of AD. Up to date, donepezil, rivastigmine and galantamine represent the only ChE inhibitors approved for AD treatment. The first ChE inhibitor was tacrine, which was withdrawn from market due to its toxicity and adverse effects. Recently, novel tacrine and 7-methoxytacrine (7-MEOTA) derivatives were synthetized and extensively investigated to find less toxic compounds affecting pathological mechanisms associated with development of AD. There is less known about effects of these drugs on mitochondrial functions and cellular energy metabolism. The aim of this project is to examine in vitro effects of ChE inhibitors on energy metabolism and cellular respiration, specifically on mitochondrial electron transport chain complexes and an enzyme of the citric acid cycle - citrate synthase. Inhibitory effects...

No description available.

No description available.