Made available in DSpace on 2014-06-11T19:31:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2004-04-27Bitstream added on 2014-06-13T21:02:43Z : No. of bitstreams: 1 tanomaru_jmg_dr_arafo.pdf: 1359372 bytes, checksum: c371c19b4e6d2928a8ca3468432f3409 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O objetivo deste estudo foi avaliar o efeito do preparo biomecânico coadjuvado por diferentes soluções irrigadoras e da sua associação a um curativo de demora à base de hidróxido de cálcio em canais radiculares de dentes de cães contendo endotoxina (LPS bacteriano). Foram utilizados 137 raízes de pré-molares com vitalidade pulpar de 7 cães, cujos canais radiculares, após pulpectomia foram preenchidos por solução de LPS de Eschechia coli na concentração de 10mg/mL, por 10 dias, quando receberam os seguintes procedimentos: Nos grupos I a V foi realizado o preparo biomecânico dos canais radiculares, coadjuvado pelas seguintes soluções irrigadoras: solução de hipoclorito de sódio a 1, 2,5 e 5% (grupos I a III); solução de digluconato de clorexidina a 2% (Grupo IV); soro fisiológico (Grupo V). No grupo VI, a solução de LPS foi mantida no canal radicular durante todo o período experimental e no grupo VII, após o preparo biomecânico coadjuvado por soro fisiológico, os canais radiculares foram preenchidos por pasta à base de hidróxido de cálcio (Calen). Decorridos 60 dias, os animais foram mortos e as peças submetidas ao processamento histológico para avaliação do reparo apical e periapical. A avaliação histopatológica demostrou que, os grupos I a VI, que não receberam curativo de demora apresentaram maior intensidade de infiltrado inflamatório, espessura do ligamento periodontal e reabsorção cementária e óssea (p<0,05) do que o grupo VII, o qual recebeu curativo de demora à base de hidróxido de cálcio. Conclui-se que o preparo biomecânico coadjuvado por diferentes soluções irrigadoras não foi capaz de inativar a endotoxina. Porém, o emprego do curativo de demora á base de hidróxido de cálcio mostrou-se eficaz na inativação, in vivo, dos efeitos tóxicos da endotoxina. / The aim of this study was to evaluate the effect of biomechanical preparation with different irrigating solutions and its association with a calcium hydroxide based root canal dressing (Calen) in root canals of dogþs teeth containing endotoxin (bacterial LPS). One hundred and thirty-seven root canals of pre-molars with pulp vitality from 7 mongrel dogs were used. The root canals, after pulpectomy, were filled with LPS solution from Escherichia coli with 10mg/mL, for 10 days. Then, they were submitted to the following treatments: In the groups I to V, biomechanical preparation of root canals was done using the following irrigating solutions: 1, 2.5 and 5% sodium hypochlorite solution in the groups I to III; 2.0% digluconate chlorhexidine (Group IV); saline solution (Group V). In the group VI, LPS solution was mantained in the root canal during all the experimental period and in the group VII, after the biomechanical preparation using saline solution as irrigating solution, the root canals were filled with a calcium hydroxide based root canal dressing (Calen). After 60 days, the animals were killed and the obtained histological sections were processed for evaluation of the apical and periapical repair. The histopathological evaluation showed that, the groups I to VI, with no root canal dressing demonstrated more intensive inflammatory infiltrate, thickness of periodontal ligament and cement and osseus reabsorption (p<0,05) than group VII, that received a root canal dressing based on calcium hydroxide. In conclusion, the biomechanical preparation with different irrigating solutions didn't inativate the endotoxin. The intracanal dressing based on calcium hydroxide was efficient, in vivo, in the inativation of the deletery effects of endotoxin.

Made available in DSpace on 2014-06-11T19:24:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2002-03-11Bitstream added on 2014-06-13T20:52:13Z : No. of bitstreams: 1 tanomaru_jmg_me_arafo.pdf: 631097 bytes, checksum: f5eee4855de406ade93e179cf7947672 (MD5) / O objetivo deste estudo foi avaliar o efeito do preparo biomecânico coadjuvado por diferentes soluções irrigadoras e da sua associação a um curativo de demora à base de hidróxido de cálcio em canais radiculares de dentes de cães contendo endotoxina (LPS bacteriano). Foram utilizados 137 raízes de pré-molares com vitalidade pulpar de 7 cães, cujos canais radiculares, após pulpectomia foram preenchidos por solução de LPS de Eschechia coli na concentração de 10mg/mL, por 10 dias, quando receberam os seguintes procedimentos: Nos grupos I a V foi realizado o preparo biomecânico dos canais radiculares, coadjuvado pelas seguintes soluções irrigadoras: solução de hipoclorito de sódio a 1, 2, 5 e 5% (grupos I a III); solução de digluconato de clorexidina a 2% (Grupo IV); soro fisiológico (Grupo V). No grupo VI, a solução de LPS foi mantida no canal radicular durante todo o período experimental e no grupo VII, após o preparo biomecânico coadjuvado por soro fisiológico, os canais radiculares foram preenchidos por pasta à base de hidróxido de cálcio (Calen). Decorridos 60 dias, os animais foram mortos e as peças submetidas ao processamento histológico para avaliação do reparo apical e periapical. A avaliação histopatológica demonstrou que, os grupos I a VI, que não receberam curativo de demora apresentaram maior intensidade de infiltrado inflamatório, espessura do ligamento periodontal e reabsorção cementária e ósse (p<0,05) do que o grupo VII, o qual recebeu curativo de demora à base de hidróxido de cálcio. Concluiu-se que o preparo biomecânico coadjuvado por diferentes soluções irrigadoras não foi capaz de inativar a endotoxina. Porém, o emprego do curativo de demora à base de hidróxido de cálcio mostrou-se eficaz na inativação, in vivo, dos efeitos tóxicos da endotoxina. / The aim of this study was to evaluate the effect of biomechanical preparation with different irrigating solutions and its association with a calcium hydroxide based root canal dressing (Calen) in root canals of dog's teeth containing endotoxin (bacterial LPS). One hundred and thirty-seven root canals of pre-molars with pulp vitality from 7 mongrel dogs were used. The root canals, after pulpectomy, were filled with LPS solution from Escherichia coli with 10mg/mL, for 10 days. Then, they were submitted to the following treatments: In the groups I to V, biomechanical preparation of root canals was done using the following irrigating solutions: 1, 2, 5 and 5% sodium hypochlorite solution in the groups I to III; 2.0% digluconate chlorhexidine (Group IV); saline solution (Group V). In the group VI, LPS solution was mantained in the root canal during all the experimental period and in the group VII, after the biomechanical preparation using saline solution as irrigating solution, the root canals were filled with a calcium hydroxide based root canal dressing (Calen). After 60 days, the animals were killed and the obtained histological sections were processed for evaluation of the apical and periapical repair. The histopathological evaluation showed that, the groups I to VI, with no root canal dressing demonstrated more intensive inflammatory infiltrate, thickness of periodontal ligament and cement and osseus reabsorption (p<0,05) than group VII, that received a root canal dressing based on calcium hydroxide. In conclusion, the biomechanical preparation with different irrigating solutioons didn't inativate the endotoxin. The intracanal dressing based on calcium hydroxide was efficient, in vivo, in the inativation of the deletery effects of endotoxin.

Au milieu du XIXe siècle les pharmaciens français ont le sentiment que leur monopole sur la vente et la fabrication de médicaments est de plus en plus menacé. Ils sont en effet de plus en plus dépendants, sur le marché, d’autres professions qui délivrent des produits en gros. C’est dans ce contexte de crise que la Pharmacie centrale de France, une coopérative d’achat et de production entre pharmaciens, est fondée en octobre 1852 par François-Louis-Marie Dorvault, lui-même pharmacien. L’étude de cette coopérative nous permet de mieux comprendre les liens entre l’industrie pharmaceutique et l’officine. Les historiens de la santé ont déjà très largement montré que l’industrie pharmaceutique contemporaine plongeait ses racines dans l’officine du XIXe siècle. Trop souvent cependant on réduit cette transition à celle d’acteurs individuels. Les historiens sociaux quant à eux ont souvent opposé la grande entreprise au petit commerce, l’émergence de l’un signifiant la disparition de l’autre. Le cas de la Pharmacie centrale de France est, de ce point de vue, original, qui offre à étudier une entreprise industrielle collective portée par des pharmaciens d’officine. Ce passage à l’industrie est perçu de façon positive et nécessaire par ces coopérateurs. Aux yeux de Dorvault, la naissance de la Pharmacie centrale va consolider l’officine dans ses fonctions commerciales et scientifiques. Elle n’a pas vocation à supplanter le pharmacien mais à le soutenir en lui permettant de mieux préparer et de vendre des produits de qualité achetés à moindre coût. Le capital de l’entreprise ne cesse de croître au cours de la période, passant de un million en 1852 à 5 millions en 1878. La Pharmacie centrale est également un succès commercial. Le chiffre d’affaires se situe à 400 000 francs en 1853 et 8 millions en 1878. La puissance de l’entreprise s’incarne à travers des bâtiments (usines de Paris et de Saint-Denis) et un réseau de succursales. La complexification du marché, la croissance de l’entreprise et les exigences de rentabilité, la concurrence féroce que se livrent les grossistes répartiteurs poussent cependant la PCF à rompre progressivement avec cette ligne. L’officine, tout en consolidant son monopole sur la vente au détail, voit disparaître les fondements de ce monopole, notamment l’élection (le choix des éléments naturels entrant dans la composition du médicament) et la préparation des produits. Les procédures de contrôle, la fabrication des produits, leur diffusion sont désormais centralisées par de grandes entreprises comme la Pharmacie centrale. La PCF accélère ainsi le passage de l’officine-laboratoire vers l’officine-comptoir. Par conséquent, la PCF a joué un rôle dans la redéfinition de l'identité professionnelle du pharmacien : une activité commerciale articulée autour d'un diplôme. La PCF a renforcé l'industrialisation de la pharmacie en amont et le monopole du pharmacien en aval. / In the middle of the nineteenth century the French pharmacists have the feeling their drug’s monopoly is threatened. They are more and more dependent towards other professions as druggists, herbalists. The Pharmacie centrale de France is a purchase co-operative between pharmacists founded by a Parisian pharmacist François-Louis-Marie Dorvault in october 1852. The PCF tries to achieve corporatist and industrial’s goals and allows us to understand the links between industry and the drugstore sector. Historians have already widely shown that the contemporary pharmaceutical industry derived from the pharmacy of the XIXth century. Too often however, we reduce this transition to individual actors. The social historians have often set the big company over against shopkeepers, the emergence of the first meaning the decline of the second. The case of the Pharmacie centrale de France is original on that account, which allows us to study an industrial co-operative between pharmacists. This transition to industry is perceived in a positive and necessary way by these co-operators. For someone like Dorvault, the Pharmacie centrale de France will strengthen the pharmacy in its commercial and scientific functions. The purpose of the co-operative is not to supplant the pharmacist but to sustain him, allowing him to prepare and to sell better medications bought at a lower cost. PCF’s capital never stops increasing during the period. From one million in 1852 the capital reaches 8 millions in 1878. The PCF is also a commercial success. Sales are estimated around 400 000 F in 1853 and 8 millions in 1878. The power of the company becomes incarnated through buildings (factories of Paris and Saint-Denis) and branches network. The PCF unfolds professional, social and scientific projects like the creation of a newspaper, the Union Pharmaceutique, in 1860; the scheme of a pharmacist’s pension fund between 1854 and 1859; the scheme of a drugstore’s insurance in 1863 and 1864; or the organization of scientific concourses. The market’s complexity, the growth of big company, the profitability’s imperatives, the fierce competition between wholesalers induce however the Pharmacie centrale to break gradually with this line. The pharmacy, while strengthening its sale’s monopoly, sees the foundations of this monopoly disappear, particularly the election (the choice of the natural elements entering the composition of the medicine) and the preparation of products. Control procedures, manufacturing, distribution are henceforth centralized by big companies as the Pharmacie centrale de France. The PCF accelerate the transformation of pharmacist’s work and the transition from preparation to sale only. In consequence, the PCF played a part in the redefinition of pharmacist’s professional identity: a commercial activity articulated around a degree. The PCF strengthened pharmacy’s industrialisation above and pharmacist’s monopoly below.

A sepse grave e o choque séptico são complicações decorrentes de um processo infeccioso, associados à alta mortalidade em UTI e caracterizados por disfunção cardiovascular, renal e metabólica. A terapia farmacológica (TF) visa oferecer suporte hemodinâmico e reduzir níveis glicêmicos. Nesse cenário, o presente estudo objetivou analisar o impacto da TF e da alteração glicêmica na evolução clinica do paciente em sepse grave e choque séptico nas primeiras 72 horas.Trata-se de um ensaio clínico controlado randomizado em que os pacientes (n=46) foram alocados em grupos glicêmicos intensivo (manutenção da glicemia entre 80-110mg/dl) e convencional (manutenção da glicemia entre180-220mg/dl). Os dados foram coletados no período de 2004-2006 em um Hospital Universitário do Município de São Paulo. Na análise estatística foram usados os testes t-student, Qui-Quadrado, sendo considerados significativo p<0,05. Os resultados mostraram que a amostra foi constituída por pacientes do sexo masculino (58,7%), clínicos (78,3%) que apresentaram choque séptico (78,3%) decorrente de infecções no sistema respiratório (39,1%), com disfunção cardíaca (36,9%) e que apresentaram lesão renal aguda (56,5%). A média de idade foi de 51,6 anos. Os medicamentos de suporte mais prescritos foram noradrenalina (69,6%; 56,5%), hidrocortisona (56,5%;67,4%) e insulina (67,4%;73,9%), nas 24 e 48 h. Na comparação entre os grupos, observou-se diferença estatisticamente significante (p=0,00) na média glicêmica; não houve diferença estatisticamente significantes para as variáveis FC mínima (p= 0,68), máxima (p=0,11), PAM mínima (p=0,06) e máxima (p=0,11), no DU (p=0,23), Cr (p=0,33), volume infundido de cristalóides (p=0,10) e na mortalidade (p=0,11). A instabilidade hemodinâmica no grupo convencional foi mais duradoura e os óbitos ocorreram, apenas, entre os pacientes alocados no grupo convencional. Dessa forma, os dados sugerem que o controle glicêmico intensivo favorece o restabelecimento hemodinâmico de pacientes em choque séptico e, de certo modo, os protege do desfecho mortalidade / Severe sepsis and septic shock are complications that develop from an inflammatory process leading to high mortality in the intensive care unit (ICU) and characterized by cardiovascular, renal and metabolic dysfunction. The pharmacological therapy (PT) aims at offering hemodynamic support and at reducing glycemic levels. In this scenario, the present study had the objective of analyzing the impact of PT and of the glycemic alteration in the clinical evolution of severe sepsis and septic shock patients in the first 72 hours. This is a randomized control trial in which the patients (n=46) were divided into intensive glycemic group (maintenance of glycemia between 80-110mg/dl) and conventional glycemic group (maintenance of glycemia between 180-220 mg/dl). The data were collected in the 2004-2006 period in a University Hospital in the city of São Paulo. In the statistical analysis, the tests used were t-student, Qui-Quadrado, being considered meaningful p<0,05. The results showed that the sample was formed by male patients (58.7%), clinical patients (78.3%) that presented septic shock (78.3%) as a result of infection in the respiratory system (39.1%), with cardiac dysfunction (36.9%) and those that presented acute renal lesion (56.5%). The average age was 51.6 years. The most commonly prescribed support drugs were noradrenaline (69.6%, 56.5%) and hydrocortisone (56.5%, 67.4%) in the first 24 and 48 hours. In the comparison between groups, statistically significant difference was observed (p=0,00) in the glycemic average, there was no statistically significant difference for the variables: minimal FC (p=0,68), maximum (p=0,11), minimum PAM (p=0,06) and maximum (p=0,11), DU (p=0,23), CR (p=0,33), volume infundido de cristalóides (p=0,10) and mortality (p=0,11). The hemodynamic instability in the conventional group lasted longer and deaths occurred only among the conventional group patients. Therefore, the data suggest that the intensive glycemic control favors the hemodynamic recovery of septic shock patients and, in a way, protects them from death

La présence de résidus de médicaments a été évaluée dans des eaux superficielles et des effluents de huit stations d'épuration (quatre rejetant dans l'estuaire de Seine dans le cadre du projet Medseine financé par le GIP Seine- Aval, quatre dans le cadre du projet Toxstep financé par l'Anses (ex-Afsset). Une centaine de molécules a été systématiquement recherchée dans les deux types d'eaux en appliquant des méthodologies analytiques impliquant une extraction solide liquide suivie une analyse par LC-MS/MS. Un suivi saisonnier des rejets de médicaments a été effectué également. Des résidus de médicaments ont été systématiquement quantifiés dans les deux types d'eaux. Les concentrations mesurées dans des eaux de surface sont significatives pour certains composés : de 1 à 108 ng/L pour diclofénac, de 2 à 324 ng/L pour ibuprofène. Pour d’autres, les valeurs sont beaucoup plus faibles : de 2 à 13 ng/L pour sulfapyridine, de 1 à 5 ng/Lpour nordiazépam. Dans les effluents de STEP, les anti-inflammatoires, les β-bloquants, les macrolides et les fluoroquinolones sont plus souvent détectés. Leurs concentrations peuvent varier fortement : de 62 ng/L à 10 μg/L pour sotalol, de 39 ng/L à 8 μg/L pour aténolol et plus particulièrement de 32ng/L jusqu’à 127 μg/L pour paracétamol. Par ailleurs, la stabilité des résidus de médicaments vis à vis des rayonnements lumineux a été évaluée. Des irradiations UV (à 254 nm) pouvant potentiellement être utilisés en étape finaleavant rejet dans des zones particulièrement sensibles ont été appliquées (avec des doses allantjusqu'à 1500 J/m2. Par ailleurs, compte tenu du fait que les effluents sont ensuite majoritairement rejetés dans des eaux superficielles, ils sont soumis aux rayonnements solaires et cette exposition a également été évaluée. Le phénomène de photodégradation à 254 nm a été bien observé sur certains composés comme diclofénac, kétoprofène (> 90% dégradé), ciprofloxacine,norfloxacine (jusqu’à 75% dégradé). L’azithromycine, la clarithromycine, la carbamazépine et l’aténolol... sont des composés plus stables avec les rayonnements lumineux. En exposant sous lumière solaire simulée, le diclofénac, la kétoprofène, la ciprofloxacine et la norfloxacine sontaussi des composés sensibles (> 90% dégradé) après 24 h d’exposition (172,8 kJ/m2). La carbamazépine, la sulfaméthoxazole, l’aténolol, bisoprolol et métoprolol sont des composés plus stables observés. / The presence of pharmaceuticals was evaluated in Seine surface waters and in eight wastewater treatment plants (WWTP) effluents (4 WWTP within MEDSEINE - GIP Seine – Aval project and 4 WWTP within TOXSTEP – ANSES project. A hundred molecules was systematically reseached in both types of waters by applying the analytical methodologies (SPE solid phase extraction followed by LC-MS/MS analysis). A seasonal monitoring of pharmaceutical residues was also carried out. The pharmaceutically residues have been systematically quantified in this both types of water. The concentrations in suface of waters are significative for some molecules: 1 – 108 ng/L for diclofenac, 2 – 324 ng/L for ibuprofen and the values are weakly for some molecules: 2 – 13 for sulfapyridine, 1 – 5 for nordiazepam. Non steroidal anti-inflammatory drugs, β-blockers, macrolides and fluoroquinolones are mostly founded in the effluents of WWTP. Their concentrations were measured in the range: 62 ng/L – 10 µg/L for sotalol, 39 ng/L – 8 µg/L for atenolol, 32 ng/L – up to 127 µg/L for paracetamol.Moreover, the stability of pharmaceuticals was evaluated with light radiation . UV irradiation (at 254 nm) potentially used in the final WWTP before discharge in particularly areas have been applied (with a dose up to 1500 J/m2). Sunlight simulations have also been done. The phenomenon of photodegradation at 254 nm has been observed for some molecules such as : diclofenac, ketoprofen (>90% degraded), ciprofloxacine, norfloxacine (up to 75% degraded). Azithromycinem clarithromycine, carbamazepine and atenolol are most stable molecules observed. Exposing under simulated sunlight, diclofenac, ketoprofen, ciprofloxacine and norfloxacine are also sensitive molecules (>90 % degraded) after 24 hours of exposure (172.8 kJ/m2). Carbamazepine, sulfamethoxazole, atenolol, metoprolol and bisoprolol are most stable molecules observed.

A comparison of the antimicrobial efficacy of silver diamine fluoride and silver nitrate on various cariogenic bacteria: an ex vivo study By: Reham AlNajjar, D.D.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Dentistry at Virginia Commonwealth University. Virginia Commonwealth University, 2019 Thesis Advisor: William Dahlke, D.M.D., Associate Professor and Chair of Pediatric Dentistry, School of Dentistry Purpose: The use of silver-based antimicrobials is an emerging method for the treatment of dental caries. In this study, the authors compare the efficacy of the two most prominent silver- based therapeutics, silver diamine fluoride (SDF) and silver nitrate (AgNO3), on cariogenic and non-cariogenic multispecies biofilms. Currently there is a lack of studies comparing the efficacy of SDF to AgNO3. Methods: Plaque samples from anterior and posterior tooth sites from children presenting both with early childhood caries and caries-free children were collected, pooled, and utilized to create four ex vivo biofilm systems in artificial saliva. SDF and AgNO3 were administered to these biofilms and bacterial survival was quantified and compared to untreated controls. Results: Each of the four pooled sample types was applied to plates coated in artificial saliva + 1% sucrose. Both SDF and AgNO3 were very effective against plaque derived biofilms when compared to untreated biofilms (P0.05) in the potency of each compound. Conclusions: SDF and AgNO3 significantly inhibit ex vivo cariogenic and non-cariogenic biofilms at similar levels.

A sepse grave e o choque séptico são complicações decorrentes de um processo infeccioso, associados à alta mortalidade em UTI e caracterizados por disfunção cardiovascular, renal e metabólica. A terapia farmacológica (TF) visa oferecer suporte hemodinâmico e reduzir níveis glicêmicos. Nesse cenário, o presente estudo objetivou analisar o impacto da TF e da alteração glicêmica na evolução clinica do paciente em sepse grave e choque séptico nas primeiras 72 horas.Trata-se de um ensaio clínico controlado randomizado em que os pacientes (n=46) foram alocados em grupos glicêmicos intensivo (manutenção da glicemia entre 80-110mg/dl) e convencional (manutenção da glicemia entre180-220mg/dl). Os dados foram coletados no período de 2004-2006 em um Hospital Universitário do Município de São Paulo. Na análise estatística foram usados os testes t-student, Qui-Quadrado, sendo considerados significativo p<0,05. Os resultados mostraram que a amostra foi constituída por pacientes do sexo masculino (58,7%), clínicos (78,3%) que apresentaram choque séptico (78,3%) decorrente de infecções no sistema respiratório (39,1%), com disfunção cardíaca (36,9%) e que apresentaram lesão renal aguda (56,5%). A média de idade foi de 51,6 anos. Os medicamentos de suporte mais prescritos foram noradrenalina (69,6%; 56,5%), hidrocortisona (56,5%;67,4%) e insulina (67,4%;73,9%), nas 24 e 48 h. Na comparação entre os grupos, observou-se diferença estatisticamente significante (p=0,00) na média glicêmica; não houve diferença estatisticamente significantes para as variáveis FC mínima (p= 0,68), máxima (p=0,11), PAM mínima (p=0,06) e máxima (p=0,11), no DU (p=0,23), Cr (p=0,33), volume infundido de cristalóides (p=0,10) e na mortalidade (p=0,11). A instabilidade hemodinâmica no grupo convencional foi mais duradoura e os óbitos ocorreram, apenas, entre os pacientes alocados no grupo convencional. Dessa forma, os dados sugerem que o controle glicêmico intensivo favorece o restabelecimento hemodinâmico de pacientes em choque séptico e, de certo modo, os protege do desfecho mortalidade / Severe sepsis and septic shock are complications that develop from an inflammatory process leading to high mortality in the intensive care unit (ICU) and characterized by cardiovascular, renal and metabolic dysfunction. The pharmacological therapy (PT) aims at offering hemodynamic support and at reducing glycemic levels. In this scenario, the present study had the objective of analyzing the impact of PT and of the glycemic alteration in the clinical evolution of severe sepsis and septic shock patients in the first 72 hours. This is a randomized control trial in which the patients (n=46) were divided into intensive glycemic group (maintenance of glycemia between 80-110mg/dl) and conventional glycemic group (maintenance of glycemia between 180-220 mg/dl). The data were collected in the 2004-2006 period in a University Hospital in the city of São Paulo. In the statistical analysis, the tests used were t-student, Qui-Quadrado, being considered meaningful p<0,05. The results showed that the sample was formed by male patients (58.7%), clinical patients (78.3%) that presented septic shock (78.3%) as a result of infection in the respiratory system (39.1%), with cardiac dysfunction (36.9%) and those that presented acute renal lesion (56.5%). The average age was 51.6 years. The most commonly prescribed support drugs were noradrenaline (69.6%, 56.5%) and hydrocortisone (56.5%, 67.4%) in the first 24 and 48 hours. In the comparison between groups, statistically significant difference was observed (p=0,00) in the glycemic average, there was no statistically significant difference for the variables: minimal FC (p=0,68), maximum (p=0,11), minimum PAM (p=0,06) and maximum (p=0,11), DU (p=0,23), CR (p=0,33), volume infundido de cristalóides (p=0,10) and mortality (p=0,11). The hemodynamic instability in the conventional group lasted longer and deaths occurred only among the conventional group patients. Therefore, the data suggest that the intensive glycemic control favors the hemodynamic recovery of septic shock patients and, in a way, protects them from death

Orientador: Idomeo Bonetti Filho / Banca: Lea Assed Bezerra da Silva / Banca: Pedro Felício Estrada Bernabé / Resumo: O objetivo deste estudo foi avaliar o efeito do preparo biomecânico coadjuvado por diferentes soluções irrigadoras e da sua associação a um curativo de demora à base de hidróxido de cálcio em canais radiculares de dentes de cães contendo endotoxina (LPS bacteriano). Foram utilizados 137 raízes de pré-molares com vitalidade pulpar de 7 cães, cujos canais radiculares, após pulpectomia foram preenchidos por solução de LPS de Eschechia coli na concentração de 10mg/mL, por 10 dias, quando receberam os seguintes procedimentos: Nos grupos I a V foi realizado o preparo biomecânico dos canais radiculares, coadjuvado pelas seguintes soluções irrigadoras: solução de hipoclorito de sódio a 1, 2, 5 e 5% (grupos I a III); solução de digluconato de clorexidina a 2% (Grupo IV); soro fisiológico (Grupo V). No grupo VI, a solução de LPS foi mantida no canal radicular durante todo o período experimental e no grupo VII, após o preparo biomecânico coadjuvado por soro fisiológico, os canais radiculares foram preenchidos por pasta à base de hidróxido de cálcio (Calen). Decorridos 60 dias, os animais foram mortos e as peças submetidas ao processamento histológico para avaliação do reparo apical e periapical. A avaliação histopatológica demonstrou que, os grupos I a VI, que não receberam curativo de demora apresentaram maior intensidade de infiltrado inflamatório, espessura do ligamento periodontal e reabsorção cementária e ósse (p<0,05) do que o grupo VII, o qual recebeu curativo de demora à base de hidróxido de cálcio. Concluiu-se que o preparo biomecânico coadjuvado por diferentes soluções irrigadoras não foi capaz de inativar a endotoxina. Porém, o emprego do curativo de demora à base de hidróxido de cálcio mostrou-se eficaz na inativação, in vivo, dos efeitos tóxicos da endotoxina. / Abstract: The aim of this study was to evaluate the effect of biomechanical preparation with different irrigating solutions and its association with a calcium hydroxide based root canal dressing (Calen) in root canals of dog's teeth containing endotoxin (bacterial LPS). One hundred and thirty-seven root canals of pre-molars with pulp vitality from 7 mongrel dogs were used. The root canals, after pulpectomy, were filled with LPS solution from Escherichia coli with 10mg/mL, for 10 days. Then, they were submitted to the following treatments: In the groups I to V, biomechanical preparation of root canals was done using the following irrigating solutions: 1, 2, 5 and 5% sodium hypochlorite solution in the groups I to III; 2.0% digluconate chlorhexidine (Group IV); saline solution (Group V). In the group VI, LPS solution was mantained in the root canal during all the experimental period and in the group VII, after the biomechanical preparation using saline solution as irrigating solution, the root canals were filled with a calcium hydroxide based root canal dressing (Calen). After 60 days, the animals were killed and the obtained histological sections were processed for evaluation of the apical and periapical repair. The histopathological evaluation showed that, the groups I to VI, with no root canal dressing demonstrated more intensive inflammatory infiltrate, thickness of periodontal ligament and cement and osseus reabsorption (p<0,05) than group VII, that received a root canal dressing based on calcium hydroxide. In conclusion, the biomechanical preparation with different irrigating solutioons didn't inativate the endotoxin. The intracanal dressing based on calcium hydroxide was efficient, in vivo, in the inativation of the deletery effects of endotoxin. / Mestre

The first chapter describes a development of the pharmaceutical industry and its market. The attention is especially paid to the pharmaceutical industry of France which is considered to be a representative of the European pharmaceutical industry. The second chapter is focused on the pharmaceutical company marketing and a medicament regarded as a product and presented from its creation to a distribution to a final consumer.

Le circuit du médicament à l’hôpital comporte quatre principales phases successives pour la prise en charge du patient hospitalisé : prescription, dispensation, administration, suivi du traitement. Toutefois, le médicament en tant que produit dispose traditionnellement d’un circuit logistique comprenant les étapes de sélection, achat et gestion de stocks. Chacune de toutes ces étapes du circuit du médicament fait intervenir différents acteurs et la pharmacie hospitalière en reste l’organe pivot à l’hôpital. La performance et la sécurisation du circuit du médicament font partie intégrante d’un système de santé efficace et doivent constituer une priorité du système de soins.Madagascar se trouve dans un contexte d’extrême pauvreté alors que 40% des dépenses de santé sont à la charge des ménages. Dans ce contexte, l’opérationnalité d’une pharmacie hospitalière est essentielle dans les hôpitaux publics dont les utilisateurs principaux sont particulièrement les populations de classe moyenne ou pauvre. Or, cette pharmacie hospitalière n’est qu’en phase de structuration à ce jour pour deux raisons : le manque d’effectifs pharmaceutiques disponibles pour ce secteur et la politique pharmaceutique hospitalière nationale encore mal définie.L'objectif de cette thèse est de contribuer à l’amélioration de l’accessibilité et de la qualité des soins de la population dans les hôpitaux publics de Madagascar en proposant un modèle optimal et justifié du circuit du médicament en tenant compte des ressources humaines, matérielles et financières. Dans une première étape, afin de compléter la littérature grise disponible au pays, une description et une analyse de l’organisation et du fonctionnement de la pharmacie hospitalière ainsi que de tout le circuit du médicament dans les hôpitaux publics ont été réalisées par une recherche qualitative. Pour cela, des interviews semi-structurés des acteurs de santé du circuit ont été menés. Les résultats mettent en évidence les lacunes en termes de cadrage de l’organisation et du fonctionnement de la pharmacie hospitalière à Madagascar. Le circuit du médicament est compliqué : sans méthode standardisée de référencement des médicaments, quantification des besoins ne tenant pas compte de méthodes validées, gestion des stocks manuelle rendant difficile la supervision, prescription sans protocoles thérapeutiques standards, délivrance nominative par du personnel non qualifié, administration sans assistance pharmaceutique. Par la suite, un focus sur l’approvisionnement, l’essentiel des activités actuelles de la pharmacie hospitalière malgache dans le circuit du médicament, a été réalisé dans un établissement hospitalier de référence choisi. Une étude rétrospective évaluative du circuit de médicaments traceurs : les antidouleurs a été menée. Les principaux indicateurs sont des indicateurs harmonisés de gestion des achats et des stocks définis par l’OMS. Le calcul des différents indicateurs montre un système d’approvisionnement suboptimal. Les pratiques de référencement, d’achat, de commande et de gestion des médicaments devront être définies. Pour arriver à cerner les priorités stratégiques de mise en œuvre de ces améliorations à Madagascar, une enquête d’évaluation auprès des acteurs de santé les plus impliqués dans le circuit du médicament a été conduite sur les 75 recommandations internationales sur le futur de la pharmacie hospitalière en terme de leur importance, de leur capacité de mise en œuvre efficace et de leur réalisabilité. 32/75 (42,7%) de ces recommandations internationales pourraient être priorisées. Sur la base de tous ces préalables, un modèle optimal d'organisation du circuit du médicament à l’hôpital est proposé et sera mis à la disposition du Ministère de la Santé pour être testé dans les hôpitaux publics. Le modèle visera principalement une « pharmaceutisation » des ressources humaines et des différentes étapes du circuit du médicament. / Hospital drug supply chain consists of four major phases in patient management: prescription, dispensing, administration and monitoring of the treatment. However, as a product, medicine has traditionally logistic supply chain including selection, procurement and stock management. Each of these steps of drug supply chain involves different actors but hospital pharmacy remains their focal point in hospital. Drug supply chain performance and safety are essential parts of an effective health care system and had become priorities for public health.Madagascar is a very poor country whereas 40% of health expenditures in charge of households. In this context, making operational the hospital pharmacy is essential in public hospitals whose main users are especially the middle class and the poor. Yet, hospital pharmacy is only on a structuring phase for two reasons: the lack of available pharmacists for this sector and the unclear national pharmaceutical policy for hospitals.The objective of this thesis is to contribute to the improvement of accessibility and quality of public health care in public hospitals of Madagascar by providing a proposal of an optimal and justified model of drug supply chain taking account the human, material and financial resources.First, description and analysis of hospital pharmacies and the drug supply chain in public hospitals were done from qualitative research. For that purpose, semi-structured interviews have been conducted with health actors of the supply chain. The principal issue perceived by interviewees was the heterogeneity of the system in terms of technical and financing management. The drug supply chain is not under control: no internal procedure has been established for the selection of pharmaceutical products, the quantification of needs is complex, the stock management is difficult to supervise, a standard prescription protocol is lacking, the dispensing is performed by unqualified staff, no pharmaceutical preparation is manufactured in the hospitals and the administration occurs without pharmaceutical support. Then, we focused on procurement, the essential of current activities of Malagasy hospital pharmacies in drug supply chain. Our retrospective and evaluative study was conducted in a university hospital and utilized indicators for assessing the procurement management of medicines and preventing stock-outs and overstocking. The calculations of these indicators show a suboptimal drug supply chain. The drug supply chain needs some improvements. In order to define some strategic priorities of the implementation of these improvements, a survey on health actors was conducted in line with the international recommendations for hospital pharmacy. 32/75 (42,7%) of these recommendation could be conducted according to the participants. An optimal organizational model of drug supply chain is proposed and will be made available to the Ministry of health to be tested in public hospitals. This model aims at implementing the « pharmaceutization » of the resources and the different steps of the drug supply chain.