Thesis (MSc) Stllenbosch University, 2001. / ENGLISH ABSTRACT: A prospective study was conducted in 1999 to establish the incidence and nature of acute poisonings in the Cape Town / Western Cape region. This study was based on an analysis of Poison Centre queries and acute poisoning admissions to Tygerberg Hospital over a period of 1 year (1999). Summary of findings for Hospital admissions (1010 cases): Acute poisonings were more common in adults (83%) than in children (17%) and drug overdose was by far the most common clinical entity in adult Hospital admissions (89% of cases). Most overdoses in adults were intentional (97%). Seventy five percent of these cases were female, predominantly in the 20-40 year age group. The incidence of non-drug chemical exposures in adults was relatively low (11%). In children, on the other hand, there was much less of a discrepancy between drug and non-drug chemical exposures (41% and 59% respectively). Paracetamol was the drug most commonly used in overdose in both adults and children. In adults ethanol featured in 17% of cases. Ingestion of paraffin and related volatile hydrocarbons were the most important cause of acute poisoning in children. Acute poisoning admissions due to drugs of abuse, excluding ethanol, were minimal in both age groups (1%). Toxic exposures to non-drug chemicals in the agricultural and industrial settings were low (3%). The number of exposures to biological toxins was also minimal (2%). Summary of findings for Poison Centre inqueries (3744 consultations): In 1999 the Tygerberg Poison Information Centre received 3744 calls, of which 2690 were related to acute human exposures to poisonous substances. The remainder of the calls (1054) was either about drug therapy, or general non-patient related toxicological matters. There were more calls regarding poisoning in adults (61%) than in children (39%). Most of the paediatric poisonings were accidental (97%), whereas in adults 55% were deliberate and 45% accidental. Forty four percent of the children and 52% of adults were female. In children, inqueries about exposures to potentially harmful non-drug household chemical products comprised 56% of poison calls, while drug overdose was 28% and exposures to biological toxins 16%. In adults 44% of inqueries were with regard to household products, 40% about drugs and 16% biological toxins. A comparison of Hospital admissions versus Poison Centre consultations: In order to make a valid comparison between Hospital admissions and Poison Centre consultations, acute poisoning cases originating from the same area were compared. Eight hundred and thirty four (90%) of patients admitted to Tygerberg Hospital and 592 (25%) of Poison Centre consultations originated from the same region, the Tygerberg catchment area. Several differences were noted when comparing poisoning cases reported to the Poison Centre and Hospital admissions. Six hundred and eighty eight (83%) adults and 145 (17%) children were admitted to Hospital in contrast to Poison Centre inqueries, where 322 (54%) were adults and 270 (46%) children. In adults, 99% of Hospital admissions versus 59% of Poison Centre consultations were regarded as self-inflicted. Ninety three percent of adults admitted to Hospital were drug overdoses, whereas only 48% of adult Poison Centre consultations involved ingestion of medicines. In adult overdoses with paracetamol and other analgesics, tricyclic antidepressants, antiepileptics, theophylline and ethanol were significantly higher in Hospital admissions than in Poison Centre consultations. In contrast, exposures to pesticides e.g. pyrethroids, misuse of recreational drugs e.g. cannabis and biological toxin exposures e.g. spider bites, were significantly higher in Poison Centre consultations than in Hospital admissions. In children, poisoning exposures to volatile hydrocarbons, especially paraffin, were significantly higher in Hospital admissions compared to Poison Centre enqueries. As is evident from the disparity in the results above, inqueries to the Tygerberg Poison Information Centre cannot be regarded as a reflection of the true incidence of acute poisonings in the community. Poison Information Centre statistics are distorted because of two factors: 1. Under-reporting to the Poison Information Centre. Healthcare providers are familiar with how to manage drugs commonly used in overdose (e.g. paracetamol) and certain household non-drug chemicals (e.g. paraffin), and often do not consult the Poison Centre for poison cases involving these substances. The number of inqueries received by the Poison Information Centre regarding these substances is, therefore, an under representation of actual incidence. 2. Over-reporting to the Poison Information Centre. The Tygerberg Poison Information Centre is well known for its expertise in biological toxins (e.g. spider and snake bites, scorpion stings, plant and mushroom ingestions, and marine toxins). Therefore, the number of inqueries received by the Centre with regard to these exposures is far higher than actual incidence of exposures. It is clear from this study that one cannot use data derived from a poison centre alone as an indicator of true incidence of poisoning in the community. A more accurate estimate of incidence of acute poisoning could be obtained by including data from hospital admissions, as well as those from primary health care facilities. Another prominent finding in this study was the high incidence of self-inflicted drug overdose in adult females, with paracetamol being the drug of choice. Poison prevention should therefore not be limited to children. Adult prevention programs need urgent attention. / AFRIKAANSE OPSOMMING: ‘n Prospektiewe studie om die insidensie en aard van akute vergigtigings in die Wes-Kaap vas te stel, is gedurende 1999 in Tygerberg Hospitaal uitgevoer. Die studie is gebaseer op ‘n analise van oproepe wat deur die Tygerbergse Vergifinligtingsentrum ontvang is en pasiente wat gedurende dieselfde tydperk met ‘n diagnose van akute vergiftiging by die Hospitaal toegelaat is. Qpsomming van Hospitaal toelatinqs (1010 qevalle): Toelatings van akute vergiftigings was meer algemeen by volwassenes (83%) as by kinders (17%). Die meeste hospitaal toelatings (83%) by volwassenes is a.g.v. geneesmiddeloordoseing. By 97% van volwassenes was gifstowwe doelbewus ingeneem, met vroue in die meerderheid (75%). Die insidensie van vergiftigings met nie-geneesmiddel verwante gifstowwe by volwassenes was laag (11%). By kinders was daar egter ‘n meer eweredige verspreiding tussen geneesmiddel (41%) en nie-geneesmiddel verwante (59%) gifstowwe. By beide volwassenes en kinders, was parasetamol die middel wat by die meeste oordoserings betrokke was. Alkohol was by 17% van vergiftigings by volwassenes betrokke. Paraffien en verwante vlugtige substanse was die belangrikste gifstowwe betrokke by akute vergiftigings by kinders. Akute vergiftigings as gevolg van die gebruik van dwelmmiddels was laag in alle ouderdomsgroepe (1%). Vergiftigings in die landbou en industriele sektore was laag (3%). Dit was ook die geval ten opsigte van blootstelling aan biologiese toksienes (2%). Opsomminq van Tyqerberq Verqifinliqtinqsentrum konsultasies (3744 qevalle): Gedurende 1999 het die Tygerberg Vergifinligtingsentrum 3744 oproepe ontvang waarvan 2690 as gevolg van akute vergiftigings was. Die ander 1054 oproepe het gehandel oor geneesmiddel terapie of algemene, nie-pasient verwante navrae. Daar is aangetoon dat oproepe ten opsigte van akute vergiftigings by volwassenes meer algemeen was as by kinders (61% en 39% respektiewelik). By kinders was die meeste vergiftigings per ongeluk (97%), terwyl by volwassenes die meeste doelbewus (55%) was. By kinders was 44% van die vroulike geslag teenoor 52% by volwassenes. By kinders was nie-geneesmiddel gifstowwe by 56% van akute vergiftigings betrokke en geneesmiddels by 44%. By volwassenes was dit 60% en 40%, respektiewelik. ‘n Verqelvkinq ten opsigte van Hospitaal toelatinqs en Verqifsentrum konsultasies: Om ‘n geldige vergelyking tussen Hospitaal toelatings en Vergifinligtingsentrum konsultasies te maak is gevalle van akute vergiftigings afkomstig uit dieselfde geografiese gebied.vergelyk. Toelatings tot Tygerberg Hospitaal 834 (90%) en 592 (25%) oproepe wat deur die Tygerbergse Vergifsentrum ontvang is, kom uit dieselfde opvangsgebied, naamlik die Tygerbergse substruktuur. Verskeie verskille tussen die twee instansies ten opsigte van die tipe vergiftigings is aangetoon. Volwassenes 688 (83%) en 145 (17%) kinders is met ‘n diagnose van akute vergiftiging by Tygerberg Hospitaal toegelaat in teenstelling met die Inligtingsentrum konsultasies waar 322 (54%) volwassenes en 270 (46%) kinders by betrokke was. By volwassenes was 99% van die toelatings die gevolg van doelbewuste vergiftiging (paraselfmoord), terwyl dit 59% van die Inligtingsentrum se navrae was. Drie en negentig persent van die volwassenes was in die Hospital toegelaat met geneesmiddel oordosering. Heelwat minder geneesmiddel oordosering (48%) was deur die Inligtingsentrum hanteer. Parasetamol en ander analgetika, trisikliese antidepressante, anti-epilepsie middels, alkohol en teofillien oordoserings by volwassenes was beduidend hoer by Hospitaal toelatings as by Vergifsentrum konsultasies. Akute vergiftiging deur paraffien en verwante vlugtige substanse by kinders was beduidend hoer by Hospitaal toelatings as wat gevind is by Inligtingsentrum navrae. Navrae ten opsigte van pestisied vergiftiging, gebruik van dwelmmiddels en blootstelling aan biologiese toksiene was beduidend hoer as by Hospitaal toelatings. Hierdie duidelike kontrasterende data dui daarop dat die tipe navrae wat deur die Tygerberg Vergifinligtingsentrum hanteer word nie noodwendig ‘n weerspieeling van die ware insidensie van akute vergiftiging in die gemeenskap is nie. Daar is 2 hoofredes hiervoor. 1. Onderrapportering by die Inligtingsentrum. Gesondheidverskaffers (dokters, verpleegsters, aptekers ens.) is vertroud met die behandeling van sekere algemene vergiftigings soos byvoorbeeld parasetamol oordosering en paraffien inname. Hulle ag dit derhalwe onnodig om die Sentrum hieroor te konsulteer. Dit lei dus tot onderrapportering. 2. Oorrapportering by die Inligtingsentrum. Die Tygerbergse Vergifinligtingsentrum is bekend vir sy vakkundigheid ten opsigte van blootstelling aan biologiese toksiene (spinnekopbyte, slangbyte, skerpioensteke, plante-en sampioen vergiftigings, ens). Dit is om hierdie rede dat vergiftigings deur biologiese agense, geraporteer aan die Sentrum, ‘n hoer syfer verteenwoordig as wat die werklike insidensie ten opsigte van die vergiftigings is. Hierdie studie toon dat vergifinligtingsentrum data nie noodwendig ‘n indikator van die ware insidensie van akute vergiftigings in die gemeenskap is nie. Dit is dus belangrik dat hospitaaltoelatingsdata asook data van primere gesondheidsklinieke ingesluit word om sodoende ‘n beter beeld te verkry van die ware insidensie van akute vergiftigings. ‘n Opmerklike bevinding tydens die studie was die hoe insidensie van doelbewuste geneesmiddel oordosering by volwasse vroue, met veral parasetamol as die middel van keuse. Programme wat fokus op die voorkoming van akute vergiftigings in volwassenes het dringende aandag nodig.

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Bibliotecas de produtos naturais são fontes de moléculas com ações farmacológicas, com diversas aplicações biotecnológicas. Estes compostos apresentam alta especificidade para o alvo, resultante de longo processo de seleção natural, sendo interessantes como ferramentas de estudo e princípios ativos. Porém, apesar da riqueza de estruturas presentes em tais secreções, as dificuldades em obter moléculas puras em grandes quantidades, o alto custo e o tempo de purificação, tornam-se barreiras para seu uso. Assim, cada vez mais, as técnicas ômicas são usadas como uma alternativa para produção destas toxinas obtidas em maior escala. A transcriptômica, técnica que consiste na produção de biblioteca de cDNA a partir do RNA obtido da de organismo, tecido ou célula de interesse, é altamente relevante, já que identifica o material proteico que é realmente transcrito a partir do RNA obtido em determinado tempo e situação. Sapos ainda são animais pouco estudados, quando comparados a outros animais peçonhentos e venenosos, e um dos fatores responsáveis por isso é o baixo rendimento na purificação de toxinas de seu veneno. A fim de se identificar componentes presentes nas secreções do sapo R. schneideri, foi, primeiramente, realizada extração de RNA poli A+ das secreções recém obtidas das glândulas mucosas e das secreções armazenadas por 2 anos no laboratório. A secreção armazenada há dois anos revelou qualidade e quantidade mais apropriadas para o estudo e foi, portanto, usada como material de partida para a construção do transcriptoma por metodologia tradicional. Este transcriptoma resultou em 6 clones com boa qualidade, sendo que um deles, Rs02, apresentou similaridade com a região do pró peptídeo da odorranaina. Uma vez que este transcriptoma não revelou resultados satisfatórios devido à sua baixa eficiência e visando maximizar o conhecimento sobre a secreção, um novo transcriptoma foi construído usando sequenciamento de nova geração, com sequenciador Illumina e RNA total extraído do tegumento contendo glândulas mucosas de um espécime como material de partida. O novo transcriptoma resultou em aproximadamente 131 milhões de reads brutos. Os reads foram filtrados de modo que apenas aqueles com boa qualidade (Q>20) fossem submetidos à montagem de novo. Esta etapa resultou em aproximadamente 130 milhões de reads, com média de 68 pb. Os reads foram então agrupados em contigs usando o programa SOAPdenovo2-Trans e submetidos a diversas abordagens de anotação funcional. Foram encontrados cDNAs codificantes de diversos peptídeos e proteínas com potencial aplicação biotecnológica. Além da abordagem ômica, ensaios de caracterização bioquímica, como atividade enzimática, cromatografia e eletroforese, auxiliaram a detecção de protease sem relatos prévios em secreções de sapo, uma fosfolipase A2, bem como lectina e galectina. Adicionalmente, através do transcriptoma foram identificadas cobatoxinas, mucinas e ficolinas. Portanto, este trabalho foi pioneiro no entendimento molecular do veneno da glândula mucosa de R. schneideri por métodos de vanguarda e análises bioquímicas. / Natural products libraries are known as medicine molecules sources once these molecules have a high target specificity inherited from the long natural evolutionary process. Thereby, animal, plant and microorganisms\' secretions are very important to biotechnological applications. However, despite the large number of molecules that can be found in these secretions, the difficulty on obtainment enough purification yield, high cost and long purification time, besides the small secretion amount provided by the studied organism, are factors that make this kind of study even harsher. These are the reasons why omic studies are becoming an alternative to produce these toxins in a larger scale, which allow new researches. Transcriptome is a technique that consists on the production of cDNA libraries from the secretion or gland RNA, using the transcriptase reverse enzyme, which results in a holistic poison understanding. Toads are animals that are still not widely studied, if we compare them with other venomous animals, mainly because of the insufficient purification yield. Thus, the mucous gland transcriptome from Rhinella schneideri poison, a toad that is widely found in Brazilian territory, has a great relevance on the elucidation and possibility to use several kind of molecules, especially because this gland produces unknown molecules. Thereof, aiming to unravel this poison molecules, we first compared the RNA yield from fresh and two years stored mucous gland secretion. The stored secretion has shown more suitable RNA, which was used to construct a Sanger sequencing transcriptome. It resulted in 6 clones and one of them had a good hit with odorranain pro-peptide region. In order to increase the knowledge about the secretion, we turned to Next Generation Sequencing transcriptome using Illumina technologies and one specimen integument as raw material. The new transcriptome resulted in approximately 131 million raw reads. These reads were filtered so that only those with good quality (Q>20) were used to perform the assembling. The latter step resulted in approximately 130 million reads with 68 bp average length. The reads were grouped into contigs using the assembler. Then, the resulting contigs were submitted to different functional annotation approaches. We unraveled cDNAs encoding peptides and protein with biotechnological application. Besides the omic approach, assays for biochemical characterization including chromatography, electrophoresis and proteolytic assays complemented the identification of a protease for the first time in toad secretions, phospholipase A2, as much as lectins and galectins. Thus, the transcriptome also allowed the identification of cobatoxins, mucins and ficolins. Therefore, this is the first work about the molecular composition of Rhinella schneideri mucous gland poison through avant-garde methodology and biochemical anaylsis.

Le cancer est l'une des principales causes de mortalité en France, après les maladies cardiovasculaires. Il est responsable de plus de 11 millions de décès dans le monde chaque année. Le cancer résulte d'une prolifération anarchique de cellules qui mène à la formation d'une tumeur. Les cellules tumorales peuvent ensuite migrer vers d'autres tissus pour former des métastases. La chimiothérapie est l'un des traitements les plus utilisés pour traiter le cancer. Elle consiste en l'utilisation d'agents antitumoraux qui provoquent la mort cellulaire en bloquant la mitose. Dans le but d'induire cette apoptose, nous nous sommes intéressés aux poisons du fuseau mitotique, agents cytotoxiques qui ont pour cible les microtubules et qui ont la particularité de se fixer sur leur constituant majeur, la tubuline. La dynamique des microtubules joue un rôle crucial dans la multiplication cellulaire. Bloquer cette dynamique est suffisant pour bloquer la mitose. Par ailleurs, suite à cet arrêt de la polymérisation, un second mécanisme se mettrait en place, notamment au niveau des cellules endothéliales, pour empêcher la néovascularisation, ce qui inhiberait ainsi l'angiogénèse. Notre travail consiste en la conception et la synthèse de nouveaux inhibiteurs de la polymérisation de la tubuline, potentiellement anti-angiogéniques et anti-vasculaires. Il s'agit de tricycles, qui ont la particularité d'interagir spécifiquement avec le site de fixation de la colchicine, au niveau de la tubuline, ce qui inhibe la polymérisation des microtubules et par conséquent la division cellulaire. Des tests d'inhibition enzymatique et de cytotoxicité sur plusieurs lignées cellulaires cancéreuses ont été réalisés et les résultats sont présentés dans ce rapport.

Nowadays, many firms are or have already been engaged in an acquisition process, either as target or acquirer. While these companies seem confident in the potential returns of such endeavors, the positive aspect of those acquisitions has yet to be proven. There is indeed a vivid discussion among scholars, which are divided into two categories. On the one hand, there are those considering acquisitions as a source of additional knowledge that will in turn increase the innovation within the company; and on the other hand, those denigrating acquisitions, assimilating them to a “poison pill” for innovation. The purpose of this research is therefore to investigate whether the acquisitions will influence positively or negatively the innovative performance of companies involved in such processes. Using a quantitative approach, this research analyzed the R&D investments made by those companies and the issued patents gained in return. The research provides mixed results. While acquisitions seem to have a positive impact on the companies‟ innovative performance during the two years following the acquisition, this positive impact does not last and even becomes negative during the third year.

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No description available.

Poison hemlock, Conium maculatum (Apiaceae), is an invasive plant in North America with a unique toxic chemistry. Previous research on this plant has focused on identifying herbivores as potential biological control agents or describing the toxic plant alkaloids. However, none have examined the role of higher trophic levels in the food web surrounding poison hemlock. Generalist predators and food web interactions are an important component of studies investigating invasion effects, as plant or animal introductions can alter ecosystem functioning. In this study, predators in poison hemlock were sampled at the foliar and epigeal levels, resulting in 956 Carabidae and 321 Coccinellidae being collected. Predator connectedness to plant resources was quantified using molecular gut-content and chemical analyses. Foliar Harmonia axyridis (Coccinellidae) contained aphid DNA and plant chemicals, while Harpalus pensylvanicus (Carabidae) only contained alkaloids, suggesting that the ground predators were obtaining plant chemicals via alternative prey. Feeding trials between H. axyridis and their potentially toxic prey, Hyadaphis foeniculi (Aphididae), revealed that the exotic predator shows faster development when consuming aphids from poison hemlock compared to alternative diets. This study reveals that three Eurasian species may be facilitating one another, illustrating the importance of continued examination of invasive species interactions.

Pesticides, rat control or targeted placed, poisoning bait by carbofuran. These and many other ways can cause the poisoning of a wild animal. Whether targeted poiso-ning of a particular animal poison or unintentional poisoning of a non-target individu-al occurs, this behavior has always fatal consequences. The persecution of nuisance animals, such as Foxes, Martens or other predators, has an influence on the whole of the population. Often poisoning bird of prey is a White-tailed Eagle, in which case every poisoned individual has an impact on the whole of the population. Unfortu-nately, this made bait is poisoning far more animals, especially for scavengers and carnivores. This paper explores the available data of poisoning animals and maps their occurrence. The data was obtained from the database the Animal Rescue Centre and the Free Wings in the period 2009-2016. Among the most commonly accepted ani-mals in the stations was the Roe Deer with poisoning caused by the Rape. Water-borne birds were Often bothered by botulism, followed by individual poisoning with poison on the rodent and poison on the Slugs. Carbofuran was most poisoned by the White-tailed Eagle, the Common Buzzard, and the Common Raven. Among the poi-sonous species are also the endangered the Red Kite, the Black Kite, and the Golden Eagle. Furthermore, it has been found that individual years have no effect on poison-ing. The difference in the number of birds and mammals poisoning was not detected. The influence of the month on the data obtained from stations was not found, the number of carbofuran poisoning is higher in March, and especially in April. In the analysis of spatial differences, there is also a balance between most regions. The Cen-tral Bohemian and the South Bohemian regions are markedly different. Above-average numbers of carbofuran poisoning originate in the regions of the South Bohe-mia, the Vysočina, the South Moravian and the Ústecký region.

Background: Methanol poisoning survivors in their lives seen big changes, especially in sphere of quality of life. Aims: The aim of this thesis is to analyze changes in the quality of life for survivors after a methanol poisoning that took place in a large affair in 2012-2013, when there were many tens of poisoning. Sample and Methods: A cohort of 47 patients, 40 men and 7 women out of ten regions of the Czech Republic, who survived poisoning by methanol in 2012-2013. For the purpose of the research was elected standardized questionnaire WHOQOL-100, which was subsequently processed in MS Excel. Results: The research has confirmed that the quality of life has deteriorated after a methane affair. The patient said they had the biggest problems in the area of finance; Mobility; Energy and fatigue; Sleep and rest; Perception of body and appearance; Everyday activities. Highest values were recorded in the areas of Experience; Thinking, learning, memory and concentration. In conclusion, low value items are predominant and no maximum value of 20 has been recorded. Conclusion: The presented results are a clear indicator that the quality of life has deteriorated in the case of the surviving metallurgical case in the Czech Republic. Key words: quality of life, poisoning, methanol, survivors.