Digitalis in one of the most frequently prescribed drugs, especially to elderly people. The prescription of cardiac glucosides (1978) was studied by using statistics from Apoteksbolaget (the National Corpora­tion of Swedish Pharmacies). There was a threefold difference in the sales of cardiac glucosides per 1000 inhabitants in the different primary care areas. Digoxin was prescribed to 90-98 per cent of the patients, with considerable variations in the dosages. Many other factors besides the cardio-vascular morbidity were likely to cause these differences. Maintenance digitalis therapy has lately been questioned. In a retro­spective study, digitalis was discontinued in 141 geriatric patients without contraindications to digitalis withdrawal. Digoxin treatment seemed to be unnecessary in 108 patients (81 per cent), followed up two months after digoxin withdrawal. A long-term study (mean: 20,5 months) was carried out in these 108 patients. Digitalis therapy was reinstituted in 30 of 99 patients, equally distributed on the basis of clear, possible or uncertain indications. Significantly more patients (p&lt; 0,001) with atrial fibrillation compared with sinus rhythm were restarted. A prospective, randomized, double-blind placebo- controlled study in 39 out of 66 geriatric patients confirmed the results of the retrospective study. During a two-month period 32 of 37 patients (86 per cent) managed without digitalis. Eighteen out of 66 patients (27 per cent) presented contraindications to digoxin with­drawal. Those who needed digitalis were restarted mainly during the first nonth (mean: 18 days) following digoxin withdrawal. Digitalis intoxication has been studied earlier, mainly in hospitalized patients. A clinical examination and ECG of a random sample of out­patients treated with digoxin shewed that about 5 per cent were certainly intoxicated and about 2 per cent suspected of being intoxi­cated. Elderly patients are said to be more sensitive to digitalis. Eleven per cent of 66 geriatric patients were found, without doubt, to be digitalis intoxicated. The mean serum digoxin concentration was significantly higher in eight toxic patients compared with non-toxic patients, but 75 per cent of the toxic patients had serum digoxin con­centrations within or below therapeutic range. Five of these intoxi­cated patients did not need maintenance digitalis therapy. A questionnaire of 361 patients in Skellefteå and Uppsala revealed that about 45 per cent had taken digitalis for more than five years. Approximately 85 per cent took one tablet daily and stated compliance. About one fifth did not know why they were taking digoxin and about half of the patients were uncertain if they were improved, by digitalis therapy. Although digitalis intoxication is such an important clinical problem, some 55 per cent did not know about digitalis's side-effects and some 50 per cent stated that no or insufficient information had been given. Only 15 per cent were satisfied with the information they had received. A significant negative correlation between digoxin dosages and the age of the patients was found. / <p>Diss. Umeå : Umeå universitet, 1983, härtill 7 uppsatser</p> / digitalisering@umu

Le compostage est une technique de valorisation des déchets organiques en un produit stable et riche en matières humiques. Certains composts « verts » se sont révélés être de 2 à 3 fois plus efficaces sur la croissance des plantes que les composts classiques. Notre étude réalisée sur un compost fabriqué à partir de déchets végétaux a permis de suivre l’évolution de la densité et de la diversité de la microflore (bactéries, champignons) au cours du processus de maturation puis de tester l’impact de ce compost sur la diversité et l’activité de la microflore tellurique. Cette analyse a été effectuée par des techniques complémentaires : biochimiques (dosages enzymatiques), microbiologiques (cultures in vitro) et de biologie moléculaire (PCR-DGGE, Séquençage). Les résultats montrent qu’au cours de sa maturation, le compost étudié présente une baisse significative de son taux d’humidité et une augmentation sensible de son pH. Sa microflore subit une complète restructuration avec apparition de souches bactériennes susceptibles de dégrader des composés polluants comme les plastiques, les pesticides et les hydrocarbures. L’ajout de ce compost à deux types de sol présentant des propriétés physico-chimiques différentes, n’a pas montré de modifications importantes et durables de la diversité microbienne et fonctionnelle de celui-ci. Les causes de l’effet remarquable de ce compost sur la croissance végétale sont discutées. / Composting is a technique of transformation organic waste in a stable product rich in organic materials. Some "green" compost proved to be from 2 to 3 times more benefit on the growth of the plants than traditional composts. The main of this study is to follow the evolution of density and diversity of the microflora (bacteria, fungi) during the process of maturation of green compost manufactured from vegetable wastes, and to investigate the impact of this compost on the diversity and the activity of the telluric microflora. This analysis was carried out by complementary techniques: biochemical (enzymatic activity), microbiological (in vitro cultures) and molecular biology (PCR-DGGE, DNA sequencing). The results show that during its maturation, the studied compost presents a significant decrease of its water content and an appreciable increase in its pH. The microflora undergoes a complete reorganization with appearance of bacterial strain suitable for degrade polluting compounds like the plastics, the pesticides and hydrocarbons. The addition of this compost with two types of soil presenting of the different physicochemical properties, did not show significant and durable modifications of the microbial and functional diversity of this one. The causes of the remarkable effect of this compost on the vegetable growth are discussed.

This study set out to review and analyse aspects of antidepressant prescribing in children and adolescents in a section of the private health care sector of South Africa. The research was conducted in two phases, namely a literature review and an empirical investigation. The aim of the literature review was to provide background to the study by conceptualising antidepressants. The empirical review followed a retrospective, descriptive, observational design. The data employed in the study was obtained from the medicine claims database of a South African Pharmaceutical Benefit Management (PBM) company. The study population consisted of 3 611 children and adolescents receiving ≥1 antidepressants from 1 January 2010 to 31 December 2010. Basic descriptive statistics, such as frequency, prevalence, average, weighted average, standard deviation, weighted standard deviation, median, effect sizes, prescribed daily dosages and DU95% methodology were used to characterise the study sample, and were calculated using the Statistical Analysis System SAS® for Windows 9.3® program. The data were used to determine the prescribing patterns of antidepressants with regard to age, gender, geographic area, type of prescriber, the comparison of prescribed daily dosages vs. recommended daily dosages, and the prevalence of potential drug-drug interactions. Potential drug-drug interactions were identified and compiled by using various interaction compendia, whereas recommended daily dosages were identified by cross-referencing various dosage compendia. The study population consisted of 1 850 girls and 1 761 boys. The mean age of girls was 13.7 ± 3.9 years, vs. 12.3 ± 3.8 years for boys (d = 0.4). A total of 11 735 prescriptions containing 12 272 antidepressants were documented in 2010. Results of the study furthermore showed that the average number of prescriptions claimed per patient increased with age, from an average of 1.0 ± 0.28 among those up to the age of 2 years, to an average of 3.4 ± 3.21 among those 16 to 18 years of age. Prescribing with regard to age groups differed, rising gradually from birth and peaking at middle childhood for boys, whereas antidepressant use in girls increased from birth up to 6 years of age, reaching a plateau and increases again from age 13 and onward. Approximately 25% (n = 12 272) of antidepressants prescribed were either not indicated in children, or the dosages were deemed too high. More than 50% (n = 12 272) of antidepressants prescribed were in the Gauteng province. The SSRIs (selective serotonin re-uptake inhibitors) and the TCAs (tricyclic antidepressants) were the most prescribed antidepressants in both gender groups. The male-to-female ratio for the selective serotonin re-uptake inhibitors was 0.9, compared to 1.2 for the tricyclic antidepressants. The top three antidepressants prescribed were imipramine (21.8%), citalopram (15.3%) and escitalopram (14.7%, n = 12 272). Potential DDIs were observed on 284 (2.4%) (n = 11 743) prescriptions. The drug pairs with potential drug-drug interactions prescribed most, were imipramine with methylphenidate [43 cases (15.1%)] and valproic acid [38 cases (13.4%)], and followed by methylphenidate in combination with fluoxetine and sertraline [both documenting 32 cases (11.3%), respectively. The TCAs accounted for 182 (64.1%) cases of possible DDIs (drug-drug interactions), whereas combination therapy of SSRIs and TCAs accounted for 21.4% of potential DDIs. In conclusion, this study determined that there were a number of differences with regard to antidepressant prescribing in children and adolescents. Recommendations for future studies were made. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

This study set out to review and analyse aspects of antidepressant prescribing in children and adolescents in a section of the private health care sector of South Africa. The research was conducted in two phases, namely a literature review and an empirical investigation. The aim of the literature review was to provide background to the study by conceptualising antidepressants. The empirical review followed a retrospective, descriptive, observational design. The data employed in the study was obtained from the medicine claims database of a South African Pharmaceutical Benefit Management (PBM) company. The study population consisted of 3 611 children and adolescents receiving ≥1 antidepressants from 1 January 2010 to 31 December 2010. Basic descriptive statistics, such as frequency, prevalence, average, weighted average, standard deviation, weighted standard deviation, median, effect sizes, prescribed daily dosages and DU95% methodology were used to characterise the study sample, and were calculated using the Statistical Analysis System SAS® for Windows 9.3® program. The data were used to determine the prescribing patterns of antidepressants with regard to age, gender, geographic area, type of prescriber, the comparison of prescribed daily dosages vs. recommended daily dosages, and the prevalence of potential drug-drug interactions. Potential drug-drug interactions were identified and compiled by using various interaction compendia, whereas recommended daily dosages were identified by cross-referencing various dosage compendia. The study population consisted of 1 850 girls and 1 761 boys. The mean age of girls was 13.7 ± 3.9 years, vs. 12.3 ± 3.8 years for boys (d = 0.4). A total of 11 735 prescriptions containing 12 272 antidepressants were documented in 2010. Results of the study furthermore showed that the average number of prescriptions claimed per patient increased with age, from an average of 1.0 ± 0.28 among those up to the age of 2 years, to an average of 3.4 ± 3.21 among those 16 to 18 years of age. Prescribing with regard to age groups differed, rising gradually from birth and peaking at middle childhood for boys, whereas antidepressant use in girls increased from birth up to 6 years of age, reaching a plateau and increases again from age 13 and onward. Approximately 25% (n = 12 272) of antidepressants prescribed were either not indicated in children, or the dosages were deemed too high. More than 50% (n = 12 272) of antidepressants prescribed were in the Gauteng province. The SSRIs (selective serotonin re-uptake inhibitors) and the TCAs (tricyclic antidepressants) were the most prescribed antidepressants in both gender groups. The male-to-female ratio for the selective serotonin re-uptake inhibitors was 0.9, compared to 1.2 for the tricyclic antidepressants. The top three antidepressants prescribed were imipramine (21.8%), citalopram (15.3%) and escitalopram (14.7%, n = 12 272). Potential DDIs were observed on 284 (2.4%) (n = 11 743) prescriptions. The drug pairs with potential drug-drug interactions prescribed most, were imipramine with methylphenidate [43 cases (15.1%)] and valproic acid [38 cases (13.4%)], and followed by methylphenidate in combination with fluoxetine and sertraline [both documenting 32 cases (11.3%), respectively. The TCAs accounted for 182 (64.1%) cases of possible DDIs (drug-drug interactions), whereas combination therapy of SSRIs and TCAs accounted for 21.4% of potential DDIs. In conclusion, this study determined that there were a number of differences with regard to antidepressant prescribing in children and adolescents. Recommendations for future studies were made. / MPharm (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014

le volcanisme alcalin triasique du massif des Ecrins Pelvoux est très ponctuel et se met en place dans un environnement marin sous forme de coulées et de pyroclastites ; l'activité volcanique se poursuit jusqu'à l' Hettangien inférieur en milieu marin plus profond. Les pipes et les dykes d'alimentation N 10 et N ont été observés dans des secteurs recouvrant les sédiments. L'absence de déformation aux épontes des dykes témoigne de l'ascension rapide d'un magma fluide dans des fissures largement ouvertes. Ce volcanisme typiquement alcalin présente un caractère hyperpotassique franc et sa spilitisation est marquée par les minéraux habituelsde la paragenèse basse température. Les seuls minéraux ferromagnésiens-relique sont des olivines, qui par leurs déformations internes et leurs inclusions de spinelles chromifères laissent supposer une origine à partir d'un magma issu de foyers de fusion partielle sous- jacents au niveau de la zone péridotitique . On note en revanche l'absence de reliques de pyroxène ;celle -ci pourrait être attribuée à une fusion congruente ou à tout autre déséquilibre dans les conditions physicochimiques du magma. Le caractère hyperpotassique de ce volcanisme est assez voisln de celui des laves shoshonitiques, mais il n'en a pas la même signification: il est à rattacher à un mécanisme de contamination lors de la traversée d'une épaisse croûte sialique, et en aucun cas à un mécanisme de subduction. Des variations irrégulières du chimisme sont observables à l'intérieur des coulées ; elles évoquent la vidange progressive, mais en un seul épisode d'un réservoir magmatique profond. Les dosages isotopiques réalisés sur des carbonates des sédiments , sur ceux inclus dans les coulées contaminées par les sédiments, et sur les carbonates disséminés dans les filons intrusifs permettent d'observer deux lignées évolutives convergentes depuis des pôles totalement opposés. On peut émettre par conséquent l'hypothèse de deux types de carbone d'origine différente dont l'une serait d'origine mantélique ; ce qui n'exclut pas une mobilisation hydrothermale posterieure. En conclusion. ce volcanisme est géodynamiquement à relier. - soit à la période de prerifting précédant l'ouverture de la future Téthys. - soit à des fissures d'extension résultant d'un système de décrochement dans une compression Nord-Sud, liée à un rejeu de fractures hercyniennes.

Les maladies mitochondriales représentent un ensemble très divers de pathologies. Au cours de ce travail, j’ai abordé leur complexité dans deux situations différentes : les déficits humains en complexe III de la chaîne respiratoire mitochondriale et l’analyse des relations génotype/phénotype dans une cohorte de patients suspects de mutations sur un même gène nucléaire (POLG). Le complexe III joue un rôle central au sein de la chaîne respiratoire mitochondriale. Contrairement à sa caractérisation biochimique très complète, son rôle physiologique a été relativement mal établi. D'une cohorte de 2000 patients dont les activités de la chaîne respiratoire mitochondriale avaient été mesurées sur tissu hépatique ou musculaire, nous avons sélectionné 15 patients avec un déficit en complexe III pour lesquels nous disposions de fibroblastes exprimant un déficit respiratoire. L’origine génétique était initialement connue pour quatre des déficits (UQCRB, BCS1L x2, MT-CYB) et, au cours de ce projet, nous avons pu en identifier trois autres (CYC1, MT-CYB, LYRM7). Nous avons cherché à évaluer l'existence d'un lien entre le phénotype et les caractéristiques du déficit : gène impliqué, distribution tissulaire et profil des réponses cellulaires au déficit. Notre population de fibroblastes, hétérogène sur le plan génétique, s’est également révélée très variée quant aux conséquences biochimiques et cellulaires du déficit. Il ne semble donc pas exister de « profil type » des déficits en complexe III. Les atteintes liées à une mutation du gène POLG sont souvent considérées comme les maladies mitochondriales les plus fréquentes chez l’adulte. Elles sont associées à des présentations cliniques très diverses. Nous avons étudié la spécificité et la sensibilité des différents signes cliniques et biologiques considérés comme évocateurs et conduisant donc au séquençage de POLG. A cette fin, nous avons analysé rétrospectivement le phénotype clinique et les investigations mitochondriales chez 154 patients dont le séquençage du gène POLG avait été effectué révélant des mutations touchant les deux allèles du gène chez 34 patients, une seule mutation chez 10 patients et une séquence normale chez 110 patients. L’étude clinique a inclus les signes/symptômes cliniques, les données électrophysiologiques et l'imagerie cérébrale. Les investigations mitochondriales englobaient l’histologie musculaire, le dosage du lactate sanguin, la mesure des activités de la chaîne respiratoire et la recherche de délétions multiples de l’ADN mitochondrial musculaire. Cette étude a montré que les mutations du gène POLG étaient responsables de signes cliniques et paracliniques récurrents présentant donc une sensibilité et une spécificité, notamment en association, permettant de proposer un arbre décisionnel pour l’indication du séquençage du gène POLG. Cette étude a également permis d’établir l’histoire naturelle des maladies de l’adulte dues à des mutations délétères de POLG. En conclusion, la classification des maladies mitochondriales par une anomalie biochimique commune, un déficit en complexe III dans le cas présent, conduit à regrouper des atteintes très différentes, aussi bien sur le plan clinique que biochimique et cellulaire. Au contraire, même dans des affections réputées comme extrêmement diverses comme celles dues aux mutations du gène POLG, la classification par le gène atteint permet d’identifier des présentations récurrentes dans la classe d’âge étudiée, patients adultes dans le cas présent… / Mitochondrial diseases represent a very diverse set of pathologies. With this work, I approached their complexity in two different situations: phenotypic analysis of fibroblasts derived from patients with defects of the respiratory complex III and phenotypic analysis of a cohort of patients, the POLG gene of whom had been sequenced. The complex III plays a central role in the mitochondrial respiratory chain. Contrary to its complete biochemical characterization, its physiological role has been relatively poorly established. We selected 15 patients with complex III defect in liver and/or muscle and with fibroblasts expressing a respiratory defect. The genetic origin was initially known for four of these defects (UQCRB, BCS1L x2, MT- CYB) and during this project, we were able to identify three additional cases (CYC1, MT- CYB, LYRM7). We sought to assess the existence of a link between the disease phenotype and the defect characteristics: gene involved, tissue expression and cellular responses. Our population of fibroblasts, genetically heterogeneous, turned also to be diverse with respect to the biochemical and cellular consequences of the defect. A "typical" profile of complex III defect therefore does not seem to exist. Pathologies related to POLG mutations are often considered the most common mitochondrial diseases in adults. Their clinical presentation is very diverse. We have investigated the specificity and sensitivity of different clinical and biological signs considered as suggestive for POLG mutations and therefore leading to POLG sequencing. To that purpose, we retrospectively analyzed the clinical phenotype and mitochondrial investigations in 154 patients for which POLG had been sequenced revealing mutations affecting two alleles of the gene in 34 patients, one allele for 10 patients and a normal sequence for 110 patients. This study has shown that POLG mutations were responsible of recurrent clinical and paraclinical signs, whose sensitivity and specificity when considered in association allowed to propose a diagnostic flowchart for POLG sequencing. This study has also permitted to establish the natural story of diseases associated with deleterious POLG mutations in adults. In conclusion, classification of mitochondrial diseases by a common biochemical abnormality, a complex III defect in the present case, leads to group very different diseases that differ from their clinical, biochemical and cellular patterns. On the contrary, even in diseases considered highly diverse as those due to POLG mutations, classification by the affected gene allows to identify recurrent presentations in a population of adult patients with neurological presentation.

The use of cellular concrete in buildings has been increasing recently due to its advantages (low density, better thermal comfort, among others). Some norms already regulate its application for walls of one floor buildings, and normative projects, still under development, which will regulate its application with structural purposes for walls of multi-level buildings. However, there still is not a specific dosage method that relates the formulation with the compression strength for cellular concrete manufacture, moreover, there are many variables (additive dosage, generation process of air bubbles, diameter, density and volume of bubbles, use of coarse aggregates, etc.), which influence the production process that needs a better understanding. Therefore, this study had as objective to evaluate the obtaining and properties of different types of cellular concrete, with the application intensio for structural purposes in construction walls. Thus, three types of cellular concrete procedures were developed adopting dosage procedures and different materials and compositions. The first with foam generated by generators (CESP), using foaming agent chemical additive (AESP), without coarse aggregate. The second with chemical additives incorporating the air bubbles through the mechanical action of the mixer (CBAM), also without coarse aggregate. And the third with coarse aggregates (CBAMG), and incorporating additives of air bubbles. The properties were evaluated in the fresh state (density, consistency and incorporating air content) and in the hardened state (compression strength). Based on results, the production of CESP was found to be made difficult by the use of foam-generator, damaging their manufacture, despite in agreement with the normative requirements for construction applications. CBAM presented a lower variability in the manufacturing process providing a better performance. Finally, CBAMG presented an improvement in workability compared to the CBAM concrete. The highest compression strength of cellular concrete CESP, CBAM and CBAMG, at 28 days, were 6.5 MPa, 19.5 MPa and 23.5 MPa, respectively, this can be applied in walls with structural purposes. / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Atualmente o uso de concreto celular em edificações vem crescendo devido as suas vantagens (baixa densidade, melhor conforto ambiental e outras). Algumas normas já regularizam sua aplicação em paredes para edificações térreas, e projetos de normas, ainda em elaboração, que irão regularizar sua aplicação com fins estruturais em paredes de edificações de vários pavimentos. Entretanto, para a obtenção de concretos celulares ainda não existem métodos de dosagens que relacionem sua formulação com a resistência à compressão, além disso, há muitas variáveis (dosagem de aditivo, processo de geração das bolhas de ar, diâmetro, densidade e volume das bolhas, uso de agregados graúdos, etc.) que influenciam no processo de produção necessitando de um melhor entendimento. Neste sentido, o presente estudo teve como objetivo avaliar a obtenção e as propriedades de diferentes tipos de concretos celulares, com o intuito de aplicação para fins estruturais em paredes de edificações. Para isso, três tipos de concretos celulares foram desenvolvidos adotando diferentes procedimentos de dosagens, materiais e composições. O primeiro com formação de espumas geradas através de geradores (CESP), utilizando aditivo químico espumígeno (AESP), sem agregado graúdo. O segundo com aditivo químico incorporador de bolhas de ar através da ação mecânica do misturador (CBAM), também sem agregado graúdo. E o terceiro com agregados graúdos (CBAMG) e aditivos incorporadores de bolhas de ar. Foram avaliadas as propriedades no estado fresco (densidade, consistência e teor de ar incorporado) e no estado endurecido (resistência à compressão). Com base na análise dos resultados verificou-se que a produção do CESP foi dificultada pelo uso dos geradores de espuma, prejudicando sua obtenção, apesar de atender os requisitos normativos para aplicações em edificações. Já o CBAM apresentou menor variabilidade no processo de obtenção proporcionando um melhor desempenho. Quanto ao CBAMG este apresentou uma melhora na trabalhabilidade comparado aos concretos de referência CBAM. As maiores resistências à compressão dos concretos celulares CESP, CBAM e CBAMG, aos 28 dias, foram, 6,5 MPa, 19,5 MPa e 23,5 MPa, respectivamente, podendo estes serem aplicados em paredes com fins estruturais.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-10-20T13:47:58Z No. of bitstreams: 1 juliocesarrochacosta.pdf: 1044594 bytes, checksum: 36dcb55eeb5afb30dd503104cc262f69 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-10-25T12:27:57Z (GMT) No. of bitstreams: 1 juliocesarrochacosta.pdf: 1044594 bytes, checksum: 36dcb55eeb5afb30dd503104cc262f69 (MD5) / Made available in DSpace on 2016-10-25T12:27:57Z (GMT). No. of bitstreams: 1 juliocesarrochacosta.pdf: 1044594 bytes, checksum: 36dcb55eeb5afb30dd503104cc262f69 (MD5) Previous issue date: 2006-02-22 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Aphitobius diaperinus (Panzer), conhecido como o cascudinho ou "lesser mealworm" coloniza o substrato encontrado em granjas, criando-se em altas populações, causando problemas sanitários e econômicos. Eles afetam a saúde e a desempenho das aves, sendo também transmissores de agentes de doenças. Seu controle baseia-se em aplicações de inseticidas, que aumentam os custos de produção e são prejudiciais aos animais. Assim sendo, as infectividades de Heterohabditis riobravus e de Steinernema carpocapsae diante dos estádios de larva, pupa e 20 adulto deste inseto para a primeira espécie de nematóide citada, e de larva e adulto para a segunda espécie, foram avaliadas em laboratório, utilizando os seguintes tipos de substratos: cepilho + ração, papel de filtro e terra. O objetivo foi determinar o grau de virulência dos juvenis infectivos (J Is) destes nematóides em cada tratamento. Os resultados indicaram que tanto H. riobravus, quanto S. carpocapsae apresentam potencial para infectar todos os estádios de desenvolvimento da espécie A. diaperinus analisados; e que os J Is de S. carpocapsae mostraramse mais eficientes contra larvas e adultos de A. diaperinus, do que os J Is de H. riobravus, em todos os tipos de substratos testados. Como já observado em outro estudo, os estágios imaturos se mostraram mais susceptíveis aos nematóides do que os adultos. Quando comparou - se os tratamentos com as duas espécies de nematóides sobre indivíduos adultos no substrato cepilho + ração, ambiente natural da espécie a ser controlada, verificou - se que as DL50 e DL90 de J Is de S. carpocapsae, corresponderam respectivamente a apenas 54,18% da DL50 e a 40,34% da DL90, encontradas para o tratamento envolvendo o nematóide da espécie H. riobravus. / Aphitobius diaperinus (Panzer), known as cascudinho or "lesser mealworm" colonizes the substrate found at farms, developing itselves in high populations, causing sanitary and economical problems. They affect the health and performance of the birds, being also transmitters of diseases. Their control is based on the application of insecticides, which increase the production costs and are harmful to the animals. Therefore, the infectivity of Heterohabditis riobravus and of Steinernema carpocapsae in front the life stages of larvae, pupae and adult of 21 this insect - for the first mentioned species of nematode - and of larva and adult for the second species, were evaluated in laboratory, using the following types of substrate: small plane + ration, filter paper and earth. The objective was to determine the degree of virulence of the J Is of these nematodes in each treatment. The results indicated that so much H. riobravus, as well as S. carpocapsae presented potential to infect all of the life stages of development of the species A. diaperinus analyzed; and that the infective juvenile of S. carpocapsae were shown more efficient against larvae and adults of A. diaperinus, that the infective juvenile of H. riobravus, in all of the types of tested substrate. As already observed in another study, the immature life stages were shown to be more susceptible to the nematodes than the adult life stage. When we compared the treatments with the two species of adult individuals constituted by the nematodes in the substrate of small plane + ration, natural environment for the species to be controlled, we verified that DL50 and DL90 of J Is of S. carpocapsae, corresponded respectively only 54.18% of DL50 and to 40.34% of DL90, found for the treatment involving the nematode of the species H. riobravus.

L'accentuation des phénomènes de résistance aux antibiotiques augmente la difficulté d'enrayer les infections bactériennes. Afin de palier ce problème, la mise au point de nouvelles stratégies, telle la stratégie antivirulence, est essentielle. Ainsi, ce manuscrit propose une nouvelle approche thérapeutique contre les bactéries à développement intracellulaire. Les analyses génomiques ont permis de mettre en évidence l'histidinol déshydrogénase (HDH, EC 1.1.1.23), enzyme impliquée dans la biosynthèse de l'histidine, comme cible biologique pour la conception de nouveaux agents antibactériens. L'étude de l'inhibition de cette dernière permet une validation de l'approche sur Brucella suis, agent responsable de la brucellose, et un élargissement du spectre d'action des composés mis au point est envisagé par l'inhibition de HDH de Mycobacterium tuberculosis. Les travaux préliminaires nécessaires a cet élargissement sont présentés dans ce manuscrit. / The raise of antibiotic resistances increases the difficulty to eradicate bacterial infections. The development of new therapeutic approaches, such as the antivirulence strategy, is essential to limitate the impact of this phenomenon. This manuscript details a new therapeutic approach against intracellular pathogens. Genomic analyses allowed to discover new targets. The histidinol dehydrogenase (HDH, EC 1.1.1.23), which is an enzyme involved in histidine biosynthesis, has therefore be chosen for the conception of new antibacterial compounds. Inhibition studies of HDH of Brucella suis allows a validation of the strategy. In order to confirm the width of the therapeutic spectrum of synthesised compounds, the inhibition of HDH from Mycobacterium tuberculosis is envisaged and preliminary experiments are presented.

“Off-label use” is defined as the use of medicine for indications other than recommended or registered for, e.g. the prescribing of a particular active substance for a patient younger than the substance is recommended or indicated for, or different formulations or dosages of a substance (Ekins-Daukes et al., 2004:349; Stedman’s medical dictionary, 2006). Off-label prescribing is common, and fluctuates by physician, patient and drug (Eguale et al., 2012:781). Drug classes most commonly prescribed off-label include anti-asthmatic, cardiovascular drugs and antidepressants. Lee et al. (2012:140) found that 9 out of 10 antidepressants prescribed were associated with unapproved usage of antidepressants. An antidepressant can be defined as a substance that prevents or relieves depression or depressive episodes (Mosby, 2009:115). There is paucity of information on the off-label prescribing practices of antidepressants in the South African private health sector. According to Eguale et al. (2012:781), the paucity of information on off-label prescribing practices may be, in part, ascribed to the difficulty in the establishment of reasons for treatment. The objective of this study was to determine the prescribing patterns of antidepressants as well as to identify off-label prescribing of antidepressants among adults in a section of the private health sector of South Africa by using a medicine claims database. A quantitative and observational, descriptive cross-sectional design was followed in this study. Data for a period of a year, from January to December 2010 were obtained for analysis. The data set consisted of medicine claims for a total number of 1 220 289 patients, containing a total of 8 515 428 prescriptions and 20 527 777 medicine items. The study population (patients receiving antidepressants 18 years and older) accounted for 14.8% (n = 1 220 289) of the total data set. The average age of patients receiving antidepressants was 56.1 ± 16.6 (median = 56.2) (Inter quartile range = 43.3–68.1). Results of the study showed that antidepressant prescriptions accounted for 8.3% (n = 8 515 428) of all prescriptions claimed during 2010. A total 3.5 % (n = 20 527 777) of antidepressants were claimed during the study period. Using the DU90% method it was established that the majority of antidepressant medicine items were prescribed by general practitioners (i.e. 75.7%, n = 702 285) and psychiatrists (14.9%, n = 702 285). Almost 72% (n = 702 885) of antidepressant medicine items claimed for the study population were for women. The most prescribed antidepressants (based on the DU90%) were amitriptyline (20.6%, n = 702 885), citalopram (19.2%), escitalopram (14.6%), fluoxetine (11.7%), venlafaxine (5.7%), paroxetine (5.2%), duloxetine (4.4%), sertraline (3.8%), bupropion (3.1%) and mirtazapine (2.6%). Amitriptyline accounted for 82.4% of off-label prescriptions (n = 2 635), whereas escitalopram and fluoxetine accounted for 4.2% and 3.8%, respectively. The tricyclic antidepressants (TCAs) were mostly prescribed off-label for migraine, headache and sleep disorders. The off-label prescribing of selective serotonin re-uptake inhibitors (SSRIs) included menopause, schizophrenia and headache. The off-label indicated prescriptions of the serotonin and noradrenaline re-uptake inhibitors (SNRIs) were mostly for schizophrenia and other anxiety disorders. Mirtazapine, a serotonin modulator/tetracyclic antidepressant, was mostly prescribed off-label for anxiety disorders. Off-label prescriptions for bupropion, a noradrenaline and dopamine re-uptake inhibitor mainly included other anxiety disorders and attention deficit hyperactivity disorder (ADHD). Furthermore, the prescribed daily dose (PDD) of each active antidepressant for all off-label indications was determined. In conclusion: This study investigated the off-label prescribing patterns of antidepressants among adults a section of the private health sector of a South Africa, using a large medicine claims database. Recommendations for future research were made. / MPham (Pharmacy Practice), North-West University, Potchefstroom Campus, 2014