Early stage memory loss interventions: utilization, impact, and the experience of living alone.

Thesis (Ph.D.)--University of Washington, 2016-08

Characterizing bupropion metabolism, pharmacokinetics and drug-drug interaction liability

Thesis (Ph.D.)--University of Washington, 2016-06

Evaluation of molar weight and deacetylation degree of chitosan during chitin deacetylation reaction: Used to produce biofilm

Chitosan is a polysaccharide derived from chitin, mainly of crustacean shells and shrimp wastes. The utilization of chitosan is related to the molar weight and deacetylation degree of the biopolymer. The aim of this work is to study the chitin deacetylation reaction, by the viscosity average molar weight and deacetylation degree of chitosan as a function of reaction time. Deacetylation was carried out in concentrated alkaline solution, 421 g L−1, at 130◦C and the reaction occurred during 4 h. Chitosan paste obtained after 20, 90 and 240 min was used to produce biofilms, which were characterized according water vapor permeability and mechanical properties (tensile strength and percentage tensile elongation at break). During the reaction time deacetylation degree reached 93%, and a 50% reduction in the viscosity average molar weight value in relation to the value of the first 20 min of reaction was found Both reactions presented a kinetic behavior of the pseudo-first order. Biofilm produced from the paste of chitosan with high deacetylation degree showed higher water vapor permeability (WVP), tensile strength (TS) and elongation (E) when compared to films with a low deacetylation.

Evaluation of processed groundnut (Arachis hypogaea) cake meals in the feeding of Clariid catfish, Clarias gariepinus, fingerlings

Groundnut cake (GNC) meal is an important source of dietary protein for domestic animals with a cost advantage over the conventional animal protein sources used in aquaculture feed production. It would be useful to evaluate the effects of GNC processing methods on the density and nutritional values of processed GNC meals. The use of processed GNC meals in the diets of Clarias gariepinus fingerlings was evaluated. Seven iso-proteic and iso-caloric diets were formulated, replacing fish meal with roasted and boiled GNC meals, each at three inclusion levels of 30%, 35%, and 40%. Diet I is 100% fishmeal, Diet II is 30% roasted GNC meal, Diet III is 35% roasted GNC meal, Diet IV is 40% roasted GNC meal, Diet V is 30% boiled GNC meal, Diet VI is 35% boiled GNC meal and Diet VII is 40% boiled GNC meal. Results showed that the crude protein content of GNC meals was 40.5% and 40.8% in boiled and roasted GNC meals respectively; the lower protein content for processed GNC meals might be due to heat denaturation of the seed protein, with boiled GNC meal being more adversely affected. The mean weight gain of fingerlings fed roasted GNC meals ranged between 5.29 – 5.64 while for boiled GNC meals, it was between 4.60 – 5.22. Generally, fish performed better when fed diets containing roasted GNC meals, than boiled GNC meals, and compared favorably with fish fed fish meal based diet. Body mass increase, total feed increase, protein efficiency ratio and specific growth rate by C. gariepinus fingerlings in all diets, showed no significant differences, suggesting that processed GNC meals could partially replace diets for C. gariepinus fingerlings without adverse consequences. This study showed that processed GNC meals could partially replace fish meal up to 30% without significantly influencing fingerling growth and health. It is recommended that the use of fish meal as the main basal ingredient for fingerlings could be discontinued, since GNC meal was a cheaper alternative, and could replace fish meal up to 35%, without any significant adverse effects on the fingerling performance. KEYWORDS: Clarias gariepinus, Fingerlings, Groundnut cake meal, Nutrient utilization, Performance.

Combined anti-Galectin-1 and anti-EGFR siRNA-loaded chitosan-lipid nanocapsules decrease temozolomide resistance in glioblastoma: In vivo evaluation

International audience

Niosomes as Nanoparticular Drug Carriers: Fundamentals and Recent Applications

Drug delivery systems are defined as formulations aiming for transportation of a drug to the desired area of action within the body. The basic component of drug delivery systems is an appropriate carrier that protects the drug from rapid degradation or clearance and thereby enhances drug concentration in target tissues. Based on their biodegradable, biocompatible, and nonimmunogenic structure, niosomes are promising drug carriers that are formed by self-association of nonionic surfactants and cholesterol in an aqueous phase. In recent years, numerous research articles have been published in scientific journals reporting the potential of niosomes to serve as a carrier for the delivery of different types of drugs. The present review describes preparation methods, characterization techniques, and recent studies on niosomal drug delivery systems and also gives up to date information regarding recent applications of niosomes in drug delivery.

Evaluation use within a humanitarian non-governmental organization’s health care user-fee exemption program in West Africa

L’évaluation de l’action humanitaire (ÉAH) est un outil valorisé pour soutenir l’imputabilité, la transparence et l’efficience de programmes humanitaires contribuant à diminuer les inéquités et à promouvoir la santé mondiale. L’EAH est incontournable pour les parties prenantes de programme, les bailleurs de fonds, décideurs et intervenants souhaitant intégrer les données probantes aux pratiques et à la prise de décisions. Cependant, l’utilisation de l’évaluation (UÉ) reste incertaine, l’ÉAH étant fréquemment menée, mais inutilisé. Aussi, les conditions influençant l’UÉ varient selon les contextes et leur présence et applicabilité au sein d’organisations non-gouvernementales (ONG) humanitaires restent peu documentées. Les évaluateurs, parties prenantes et décideurs en contexte humanitaire souhaitant assurer l’UÉ pérenne détiennent peu de repères puisque rares sont les études examinant l’UÉ et ses conditions à long terme. La présente thèse tend à clarifier ces enjeux en documentant sur une période de deux ans l’UÉ et les conditions qui la détermine, au sein d’une stratégie d’évaluation intégrée au programme d’exemption de paiement des soins de santé d’une ONG humanitaire. L’objectif de ce programme est de faciliter l’accès à la santé aux mères, aux enfants de moins de cinq ans et aux indigents de districts sanitaires au Niger et au Burkina Faso, régions du Sahel où des crises alimentaires et économiques ont engendré des taux élevés de malnutrition, de morbidité et de mortalité. Une première évaluation du programme d’exemption au Niger a mené au développement de la stratégie d’évaluation intégrée à ce même programme au Burkina Faso. La thèse se compose de trois articles. Le premier présente une étude d’évaluabilité, étape préliminaire à la thèse et permettant de juger de sa faisabilité. Les résultats démontrent une logique cohérente et plausible de la stratégie d’évaluation, l’accessibilité de données et l’utilité d’étudier l’UÉ par l’ONG. Le second article documente l’UÉ des parties prenantes de la stratégie et comment celle-ci servit le programme d’exemption. L’utilisation des résultats fut instrumentale, conceptuelle et persuasive, alors que l’utilisation des processus ne fut qu’instrumentale et conceptuelle. Le troisième article documente les conditions qui, selon les parties prenantes, ont progressivement influencé l’UÉ. L’attitude des utilisateurs, les relations et communications interpersonnelles et l’habileté des évaluateurs à mener et à partager les connaissances adaptées aux besoins des utilisateurs furent les conditions clés liées à l’UÉ. La thèse contribue à l’avancement des connaissances sur l’UÉ en milieu humanitaire et apporte des recommandations aux parties prenantes de l’ONG.

Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-beta-cyclodextrin inclusion complex

Ropivacaine (RVC) is an enantiomerically pure local anesthetic (LA) largely used in surgical procedures, which presents physico-chemical and therapeutic properties similar to those of bupivacaine (BPV), but associated to less systemic toxicity This study focuses on the development and pharmacological evaluation of a RVC in 2-hydroxypropyl-beta-cyclodextrin (HP-P-CD) inclusion complex. Phase-solubility diagrams allowed the determination of the association constant between RVC and HP-beta-CD (9.46 M-1) and showed an increase on RVC solubility upon complexation. Release kinetics revealed a decrease on RVC release rate and reduced hemolytic effects after complexation. (onset at 3.7 mM and 11.2 mM for RVC and RVCHP-beta-CD, respectively) were observed. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and X-ray analysis (X-ray) showed the formation and the morphology of the complex. Nuclear magnetic resonance (NMR) and job-plot experiments afforded data regarding inclusion complex stoichiometry (1:1) and topology. Sciatic nerve blockade studies showed that RVCHP-beta-CD was able to reduce the latency without increasing the duration of motor blockade, but prolonging the duration and intensity of the sensory blockade (p < 0.001) induced by the LA in mice. These results identify the RVCHP-beta-CD complex as an effective novel approach to enhance the pharmacological effects of RVC, presenting it as a promising new anesthetic formulation. (c) 2007 Elsevier B.V All rights reserved.

Stability and Local Toxicity Evaluation of a Liposomal Prilocaine Formulation

This study reports a physicochemical stability evaluation of a previously reported liposomal prilocaine (PLC(LUV)) formulation (Cereda el al. J. Pharm. Pharmaceut. Sci. 7:235, 2004) before and after steam sterilization as well as its local toxicity evaluation. Prilocaine (PLC) was encapsulated into extruded unilamellar liposomes (LUVs) composed by egg phosphatidylcholine:cholesterol:alfa-tocopherol (4:3:0.07, mole %). Laser light-scattering analysis (p > 0.05) and thiobarbituric acid reaction (p > 0.05) were used to evaluate the liposomes physical (size) and chemical (oxidation) stability, respectively. The prilocaine chemical stability was followed by (1)H-nuclear magnetic resonance. These tests detected no differences on the physicochemical stability of PLC or PLCLUV, sterilized or not, up to 30 days after preparation (p > 0.05). Finally, the paw edema test and histological analysis of rat oral mucosa were used to assess the possible inflammatory effects of PLC(LUV). PLC(LUV) did not evoke rat paw edema (p > 0.05), and no significant differences were found in histological analysis, when compared to the control groups (p > 0.05). The present work shows that PLC(LUV) is stable for a 30-day period and did not induce significant inflammatory effects both in the paw edema test and in histological analysis, giving supporting evidence for its safely and possible clinical use in dentistry.

In-vitro evaluation of the quality of Paracetamol and Co-trimoxazole tablets used in Malawi based on pharmacopoeial standards

Objectives This study was an in-vitro evaluation of different brands of paracetamol and cotrimoxazole tablets, used or found in Malawi, based on Pharmacopoeia standards, in order to ascertain the existence and extent of substandard medicines in Malawi and to give an overview of their distribution in the public and private sectors. Methodology A cross-sectional analytical study was conducted using 11 samples each of paracetamol and cotrimoxazole tablets. Stratified random sampling was used to collect samples. Samples were analyzed using HPLC and Spectrophometric methods as outlined in the BP-2007 and USP-32 at the National Drug Quality Control Laboratory (NDQCL)-Lilongwe (under Pharmacy Medicines and Poisons Board-PMPB) and Orient Pharma Co. Ltd of Taiwan. The results were analyzed using Epi Info. Results and discussion Fifty percent of samples (n=22) were not registered in the country by the PMPB as required by the PMP Act with the majority of those coming from public health facilities. All paracetamol and cotrimoxazole samples complied with identification tests using spectrophotometric and HPLC method. Overall, 27.3% of samples failed to meet the BP-2007 standards for Active Ingredient content, while 22.7% of the samples failed the Friability test. The results from Malawi are similar in magnitude to those within surrounding countries in Africa. Conclusion This pilot study provides objective evidence to show that substandard and unregistered paracetamol and cotrimoxazole are present and being used in Malawi, and thus posing a considerable hazard to public health in Malawi. PMPB, together with the Ministry of Health, must continue to develop a quality assurance system to ensure that medicines are randomly and routinely checked.

Evaluation of the antioxidant activity and antitumor activity of marine invertebrates extracts

Dissertação de Mestrado, Biologia Marinha, Faculdade de Ciências e Tecnologias, Universidade do Algarve, 2014

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques. Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure. Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0-∞ , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %). Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.

Development and evaluation of floating microspheres of curcumin in alloxan-induced diabetic rats

Purpose: To prepare and evaluate floating microspheres of curcumin for prolonged gastric residence and to study their effect on alloxan-induced diabetic rats. Methods: Floating microsphere were prepared by emulsion-solvent diffusion method, using hydroxylpropyl methylcellulose, chitosan and Eudragit S 100 polymer in varying proportions. Ethanol/dichloromethane blend was used as solvent in a ratio of 1:1. The floating microspheres were evaluated for flow properties, particle size, incorporation efficiency, as well as in-vitro floatability and drug release. The anti-diabetic activity of the floating microspheres of batch FM4 was performed on alloxaninduced diabetic rats. Result: The floating microspheres had particle size, buoyancy, drug entrapment efficiency and yield in the ranges of 255.32 - 365.65 μm, 75.58 - 89.59, 72.6 - 83.5, and 60.46 - 80.02 %, respectively. Maximum drug release after 24 h was 82.62 % for formulation FM4 and 73.879, 58.613 and 46.106 % for formulations FM1, FM2, and FM3 respectively. In-vivo data obtained over a 120-h period indicate that curcumin floating microspheres from batch FM4 showed the better glycemic control than control and a commercial brand of the drug. Conclusion: The developed floating curcumin delivery system seems economical and effective in diabetes management in rats, and enhances the bioavailability of the drug.

Constraint-Informed Information Systems in Space Management Utilization

Declarative techniques such as Constraint Programming can be very effective in modeling and assisting management decisions. We present a method for managing university classrooms which extends the previous design of a Constraint-Informed Information System to generate the timetables while dealing with spatial resource optimization issues. We seek to maximize space utilization along two dimensions: classroom use and occupancy rates. While we want to maximize the room use rate, we still need to satisfy the soft constraints which model students’ and lecturers’ preferences. We present a constraint logic programming-based local search method which relies on an evaluation function that combines room utilization and timetable soft preferences. Based on this, we developed a tool which we applied to the improvement of classroom allocation in a University. Comparing the results to the current timetables obtained without optimizing space utilization, the initial versions of our tool manages to reach a 30% improvement in space utilization, while preserving the quality of the timetable, both for students and lecturers.

Evaluation of the theranostic use of miRNAs in correlation to the radiopharmaceutical 64CuCl2 in glioblastoma

B:Glioblastoma multiforme(GBM) is one of the most prevalent and aggressive malignant primary brain tumors in adult patients. 64CuCl2 is an innovative radiopharmaceutical investigated as theranostic agent in GBM patients. The therapeutic scheme is still under evaluation, therefore the research focused on the possibility of radioresistance development. The actors responsible for modulating radioresistance could be miRNAs, thus their potential use was investigated both in radioresistant cell lines and in GBM patients plasma samples. M:Radioresistant cell lines were generated by exposing U87MG, U373MG lines to increasing doses of radiation for 32 weeks. Cell membrane permeability alterations and DNA damage were assessed to characterize the lines. Moreover, 64Cu cell incorporation and subcellular distribution were investigated measuring gamma-radiation emission. miRNA expression was evaluated: in parental and radioresistant cell lines, both in cell pellet and media exosomes; in plasma samples of GBM patients using TaqMan Array MicroRNA Cards. R:Radioresistant lines exhibited reduction in membrane permeability and in DNA DSBs indicating the capability to skip the drug killing effect. Cell uptake assays showed internalization of 64Cu both in the sensitive and radioresistant lines. Radioresistant lines showed a different miRNA expression profile compared to the parental lines. 5 miRNAs were selected as possible biomarkers of response to treatment (miR-339-3p, miR-133b, miR-103a-3p, miR-32-5p, miR-335-5p) and 6 miRNAs as possible predictive biomarkers of response to treatment (let-7e-5p, miR-15a-5p, miR-29c-3p, miR-495, miR-146b-5p, miR-199a-5p). miR-32-5p was selected as possible molecule to be used to restore 64CuCl2 responsiveness in the radioresistant cell lines. C: This is the first study describing the development and characterization of 64CuCl2 radioresistant cell lines useful to implement the approach for dosimetric analysis to avoid radioresistance uprising. miRNAs could bring to a better understanding of 64CuCl2 treatment, becoming a useful tool both in detection of treatment response and both as molecule that could restore responsiveness to 64CuCl2 treatment.