Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2005. / "A dissertation in pharmaceutical sciences and chemistry." Advisor: Steven H. Neau and Thomas P. Johnston. Typescript. Vita. Description based on contents viewed Mar. 12, 2007; title from "catalog record" of the print edition. Includes bibliographical references (leaves 97-108). Online version of the print edition.

Thesis (doctoral)--Freie Universität Berlin, 1979.

No description available.

No description available.

Thesis (Ph. D. in Chemistry)--Vanderbilt University, Dec. 2008. / Title from title screen. Includes bibliographical references.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O hidroxicitronelal à um composto amplamente usado como fragrÃncia em cosmÃticos. Este composto pode ser obtido a partir da semi-sÃntese do citronelal, um terpeno isolado do Ãleo essencial de citronela (Cymbopogon marginatus) ou de cidreira (Melissa officinalis), e tambÃm vÃrias outras plantas. O objetivo deste estudo à demonstrar a atividade gastroprotetora do hidroxicitronelal em modelos de lesÃo gÃstrica aguda. A manipulaÃÃo dos animais e os protocolos experimentais foram registrados no Comità de Ãtica Institucional (CEPA) sob o nÃmero 052/2011. Foram utilizados camundongos swiss, que foram divididos em grupos de 8 (n = 8), e foram submetidos a um perÃodo de jejum de 16h, entÃo foram tratados com HC nas doses de 0.5; 2.5 e 12,5 mg/Kg ou NAC (750 mg/Kg). ApÃs 30 minutos os animais receberam 0,2 ml de etanol absoluto v.o. E apÃs 30 min, os animais foram sacrificados, os estÃmagos removidos e analisados para determinaÃÃo do Ãndice de lesÃo ou feito homogenatos para a dosagem de GSH (glutationa reduzida). A fim de se investigar o envolvimento das prostaglandinas, NO e dos canais de potÃssio, antes do tratamento com HC os animais receberam L-NAME(20mg/Kg) e/ou L-arginina(600mg/Kg), indometacina (10mg/Kg) e/ou misoprostol(0.03Âg/Kg), Glibenclamida(5mg/Kg) e/ou DiazÃxido(3mg/Kg). Para investigar a participaÃÃo dos receptores TRPV1 , os animais receberam capsaicina(0,3mg/Kg) e/ou capsazepina(5mg/Kg). No modelo de Ãlcera gÃstrica induzida por AINEs, os animais foram tratados com HC (12.5; 50 e 200 mg/Kg) ou Cimetidina (100 mg/Kg) 30 min antes do tratamento com indometacina (60 mg/Kg), e depois de 6h os animais foram sacrificados, os estÃmagos removidos e analisados sob o critÃrio de escores de lesÃo. No modelo de lesÃo por etanol, HC nas doses de 0,5; 2.5 e 12 mg/Kg foi capaz de inibir a lesÃo em 31; 53 e 69% respectivamente. HC tambÃm recuperou os nÃveis de GSH na mucosa em 31.19% quando comparados com o grupo lesÃo. L-NAME, Glibenclamida e Indometacina foram capazes de reverter o efeito de HC, demonstrando o envolvimento das Prostaglandinas, NO e dos canais de potÃssio, em seu mecanismo de aÃÃo. Capsazepina foi inefetiva em reverter o efeito de HC, assim excluindo o possÃvel envolvimento dos receptores TRPV1. No modelo de lesÃo por AINEs, HC nas doses testadas reduziu os escores de lesÃo em 28.8, 56.3, e 84.1% respectivamente. Podemos concluir que HC possui uma atividade farmacolÃgica gastroprotetora sobre a mucosa do estÃmago. Essa proteÃÃo parece ser mediada em parte pela modulaÃÃo de Prostaglandina/NO/ KATP, que à de papel fundamental na manutenÃÃo do fluxo sanguÃneo e na defesa da mucosa gÃstrica. / The hydroxycitronellal is a compound widely used as fragrance in cosmetics. This compound can be obtained by semi-synthesis from citronellal, a terpenoid isolated from essential oil of citronella (Cymbopogon marginatus) or Balm (Melissa officinalis), and also found in other plants. The aim of this study is to demonstrate the gastroprotective of hydroxycitronellal in gastric ulcer models. Animal handling and experimental protocols were registered on the Institutional Ethics Committee (CEPA) under number 052/2011. Swiss mice were used, were divided into groups of 8 (n = 8), and undergo fasting of 16h, then were treated with HC in doses 0.5; 2.5 and 12,5 mg/Kg or NAC (750 mg/Kg). After 30 min they received 0, 2 ml of absolute ethanol per oral and after 30 min, the animals were sacrificed and stomachs removed and analyzed the lesion index and dosage of GSH (reduced glutathione). In order to investigate the involvement of prostaglandins, NO and potassium channels, before treatment with HC animals received L-NAME (20mg/Kg) or L-arginine (600mg/Kg), indomethacin (10mg/Kg) or misoprostol (0.03Âg/Kg), Glibenclamide (5mg/Kg) or Diazoxide (3mg/Kg). To investigate the participation of TRPV1 receptors, animals received capsaicin (0,3mg/Kg) or capsazepina (5mg/Kg). In the model of injury by NSAIDâs, the animals were treated with HC (12.5; 50 and 200 mg/Kg) or Cimetidine (100 mg/Kg) 30 min before treatment with indomethacin (60 mg/Kg), and after 6h animals were sacrificed and stomachs removed and examined under-rated scores. In model of injury by ethanol, HC at the doses 0,5; 2.5 and 12 mg/Kg was able to prevent injury in 31.0; 52.9 and 69.3% respectively. HC also restored the GSH levels in mucosa in 31.19% compared to the ethanol group. LNAME, Glibenclamide and Indometacin were able to reverse the protective effect of HC, demonstrating the involvement of Prostaglandins, NO and potassium channels in its mechanism of action. Capsazepine was unable to reverse the effect of HC, thus excluding a possible involvement of TRPV1 receptors. In the model of injury by NSAIDâs, HC in tested doses reduces the injury scores in 28.8, 56.3, and 84.1%respectively. We can conclude that the HC has pharmacological activity with gastroprotetor effect in the gastric mucosa. This protection appears to be mediated in part by modulation of Prostaglandin/NO/KATP, which is of great importance in mucosal defense and in maintaining blood flow to the stomach.

Postendoscopic retrograde cholangiopancreatography pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography pancreatitis (ERCP). No randomized controlled trial (RCT) has compared the efficacy of the American Society of Gastrointestinal Endoscopy and European Society of Gastrointestinal Endoscopy recommended interventions for PEP prevention. We assessed the effectiveness of these interventions using network meta-Analysis. PubMed, EMBASE, and Cochrane databases were searched to identify RCTs investigating guideline-recommended interventions and their combinations [rectal nonsteroidal anti-inflammatory drugs (NSAIDs): indomethacin or diclofenac, pancreatic stent (PS), aggressive hydration (AH), sublingual nitrate) for PEP prevention. We performed direct and Bayesian network meta-Analysis, and the surface under the cumulative ranking curve to rank interventions. Subgroup network meta-Analysis for high-risk populations was also performed. We identified a total of 38 RCTs with 10 different interventions. Each intervention was protective against PEP on direct and network meta-Analysis compared with controls. Except AH+diclofenac and NSAIDs+ sublingual nitrate, AH+indomethacin was associated with a significant reduction in risk of PEP compared with PS [odds ratio (OR), 0.09; credible interval (CrI), 0.003-0.71], indomethcin+PS (OR, 0.09; CrI, 0.003-0.85), diclofenac (OR, 0.09; CrI, 0.003-0.65), AH (OR, 0.09; CrI, 0.003-0.65), sublingual nitrate (OR, 0.07; CrI, 0.002-0.63), and indomethacin (OR, 0.06; CrI, 0.002-0.43). AH with either rectal NSAIDs or sublingual nitrate had similar efficacy. AH+indomethacin was the best intervention for preventing PEP with 95.3% probability of being ranked first. For high-risk patients, although the efficacy of PS and indomethacin were comparable, PS had an 80.8% probability of being ranked first. AH+indomethacin seems the best intervention for preventing PEP. For high-risk patients, PS seems the most effective strategy. The potential of combination of interventions need to be explored further.

This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu).

No / Spherical crystallization involves crystallization and simultaneous agglomeration of a crystalline particle using an immiscible phase, which has preferential affinity for the crystal surface. Here, we report application of a spherical crystallization technique to the field of co-crystallization. Carbamazepine/saccharin (CBZ/SAC) co-crystals were generated using reverse antisolvent addition and agglomerated using different bridging liquids. Two crystal forms of CBZ/SAC co-crystals were formed, depending on the levels of supersaturation achieved during processing. The selective agglomeration of co-crystal occurred during the agglomeration stage, depending on the relative interaction between bridging liquid and the crystal surfaces. The computational investigation of isosteric heats of adsorption of the bridging liquids at the prominent crystal surfaces proved to be a useful tool in understanding the surface interactions. The spherical crystallization technique shows opportunity to generate co-crystals and its purification through selective agglomeration.

Objetivos: Avaliar a farmacocinética do éster etílico de indometacina (IndOEt) em ratos Wistar, após sua administração oral (p.o) e intravenosa (i.v.) nas formas livre ou nanoencapsulada, e monitorar a formação de indometacina (IndOH) in vivo. Metodologia: Os protocolos experimentais foram aprovados pelo Comitê de Ética em Pesquisa da UFRGS (2005478). Nanocápsulas (NC) contendo IndOEt (IndOEt- NC) foram administradas p.o. (10 mg/kg) e i.v. bolus (5 mg/kg) a ratos machos Wistar (n = 5 a 7/grupo) e as concentrações plasmáticas de IndOEt e IndOH resultantes foram determinadas por CLAE com detecção por UV, empregando-se metodologia validada. Os grupos controle foram tratados com suspensão aquosa de IndOEt (10 mg/kg), com ou sem polissorbato 80, ou com IndOH pelas vias i.v. ou p.o. (10 mg/kg) (n = 7 a 11/grupo). Os perfis plasmáticos individuais foram avaliados por abordagem não-compartimental e compartimental utilizando os softwares Excel® 2003 e Scientist® 2.01, respectivamente, para a determinação dos parâmetros farmacocinéticos, que foram comparados estatisticamente utilizando-se teste “t” de Student ou ANOVA (α = 0,05). A avaliação do local de absorção p.o. de IndOEt-NC foi realizada pela quantificação de IndOEt e IndOH no plasma periférico e da veia porta, homogeneizado de fígado e de parede, bem como conteúdo, de porções do intestino delgado (n= 4/tempo) após a administração oral da formulação. Resultados e Discussão: Após a administração de IndOEt-NC por ambas as vias, apenas a IndOH foi detectada, indicando uma rápida hidrólise do éster. Em todos os casos, o IndOEt não alterou os parâmetros farmacocinéticos da IndOH, exceto a biodisponibilidade. Os perfis plasmáticos de IndOH i.v. foram descritos pelo modelo de 2 compartimentos, e os orais, pelo de 1 compartimento com absorção de primeira ordem. A avaliação da absorção oral de IndOEt-NC evidenciou que o IndOEt é, provavelmente, liberado e hidrolisado ainda na luz do trato gastrintestinal, sendo a IndOH formada in vivo e absorvida. Conclusões: O IndOEt nanoencapsulado ou não, quando administrado pelas vias oral e i.v., é rapidamente convertido a IndOH. A IndOH é, portanto, responsável pela atividade antiedematogênica relatada para o IndOEt-NC. / Objective: To evaluate the pharmacokinetics of either nanoencapsulated (NC) or free indomethacin ethyl ester (IndOEt) after intravenous (i.v.) and oral (p.o.) administration to Wistar rats and to determine the pharmacokinetics of indomethacin (IndOH) formation. Methodology: Animal experiments were approved by UFRGS Ethics in Research Committee (# 2005478). The pharmacokinetics was investigated in male Wistar rats after oral and i.v. administration of IndOEt-NC (10 mg/kg and 5 mg/kg, respectively) (n = 5-7/group) and IndOEt and IndOH plasma concentrations were determined by a validated HPLC with UV detection method. The control groups were treated with IndOEt aqueous suspension (10 mg/kg p.o.) or with IndOH aqueous suspension by the p.o. or i.v. routes (10 mg/kg) (n = 7 -11/group). Noncompartmental and compartmental approaches were used for individual profiles analysis using Excel® 2003 or Scientist® 2.01 softwares, respectively. The site of IndOEt-NC oral absorption was investigated in peripheral and portal vein plasma, hepatic tissue, intestine epithelia, and lumen content (n = 4/time). Results and Discussion: After IndOEt administration by both routes, only IndOH was detected in plasma, suggesting a fast hydrolysis of the ester. The IndOH parameters after administration of IndOEt and IndOH were similar, except for the bioavailability. The pharmacokinetic parameters of IndOH were modeled by two compartment open model after i.v. dosing and by one compartment with first order absorption after oral administration. After oral administration, IndOEt-NC was converted in IndOH in the gastrointestinal tract and then absorbed as such. Conclusions: After i.v. and oral administration, either IndOEt-NC or the free drug is quickly converted in IndOH. After oral administration, IndOEt-NC is released and hydrolyzed to IndOH following its absorption at the gastrointestinal tract. Therefore, the IndOH is responsible for antiendematogenic activity reported for IndOEt-NC.