Biopharmaceuticals, including proteins, DNA and vaccines, are one of the fastest growing segments of the overall pharmaceutical market. While the hypodermic injection, the most common delivery method for these molecules, is effective, it also has limitations, including low patient compliance, need for medically trained personnel and biohazardous sharps after delivery. The overall goal of this thesis was to develop a new delivery system for biopharmaceuticals, based on dissolving polymer microneedles, which is effective and more patient compliant than the hypodermic needle. Microneedles are microscopic needles that are large enough to insert into the skin to deliver drugs effectively, while being short enough to avoid the pain causing nerves deep in the skin. An additional benefit of polymer microneedles is that the needles completely dissolve in the skin, leaving behind no biohazardous sharps. There are significant material and fabrication issues that must be overcome in the development of this new device. The first part of this thesis focused on the development of a new fabrication process, based on in situ photopolymerization, for the creation of polymer microneedles. These microneedles were shown to successfully insert into the skin, dissolving within a minute to deliver the encapsulated cargo, and retain full activity of encapsulated proteins. Next, we applied the microneedle technology to the delivery of the influenza virus. We found that the reformulation process required to encapsulate the influenza virus in polymer microneedles did not affect the antigenicity or immunogenicity of the virus. In addition, we used coated metal microneedles to successfully immunize mice with the influenza virus, verifying the delivery capabilities of a microneedle system. Finally, we used the dissolving polymer microneedles to successfully immunize mice with the influenza virus, resulting in full protection against lethal challenge after one immunization. This immune response was equivalent to the control intramuscular injection. In conclusion, we have developed dissolving polymer microneedles as an effective and patient compliant delivery system for biopharmaceuticals. This system could be especially applicable to mass immunization efforts or home use, since it can be self-administered and allows for easy disposal with no biohazardous sharps.

Thesis (M.Sc.)--Memorial University of Newfoundland, School of Pharmacy, 1998. / Typescript. Bibliography: leaves 106-130.

SQL injekcijos atakos taikinys – interaktyvios interneto programos, kurios naudoja duomenų bazės serverius. Šios programos leidžia vartotojams įvesti informaciją ir ją įvedus formuojamos SQL užklausos, kurios siunčiamos į duomenų bazės serverį. Darydamas SQL injekcijos ataką, atakuotojas per įvesties laukus suformuoja kenksmingą SQL užklausos segmentą, kuris modifikuoja buvusią užklausą. Naudodamas SQL injekcijos ataką, atakuotojas gali prieiti prie konfidencialios informacijos, ją modifikuoti ar, apeidamas autorizacijos scenarijų, prisijungti prie sistemos nežinodamas slaptažodžio. Šiame darbe pasiūlytas saugos modulis perima visą vartotojo įvedamą informaciją, pritaiko saugumo taisykles ir taip padidina saugumą apsisaugant nuo SQL injekcijų el. verslo žiniatinklio programose bei registruoja potencialius bandymus sutrikdyti normalų sistemos darbą. Norint įdiegti pasiūlytą saugos modulį, nereikia konfigūruoti serverio ar jo programinės įrangos – modulio diegimo metu keičiasi tik žiniatinklio programos failai. Darbui atlikti pasirinkta PHP programavimo kalba ir MySQL duomenų bazė. Tyrimo metu atlikti testavimo rezultatai parodo, kokius saugos modulio konfigūravimo parametrus reikia taikyti norint užtikrinti maksimalų saugumo lygį. / The target of SQL injection attack – interactive web programs, which use database servers. Those programs allow users to input information and as it is imputed, it forms SQL queries, which are sent into database server. With SQL injection help, the attacker using input fields forms harmful section of SQL query, which modifies previous query. Exploiting attack of SQL injection, the attacker may learn confidential information, modify it or connect to system without knowing the password by authorisation bypass. In this research-paper the proposed security model takes over all information inputted by user, adjusts the safety rules and that way it improves the safety in order to guard from SQL injections at electronic business web systems as well as it register potential attempts to disrupt normal work of the system. In order to install the proposed safety model there is no need to configure the server or its software because in the moment of installation it changes only files of website programs. For purpose of executing this work, we use PHP programming language and MySQL database. During the analysis, the received test results show what configuration parameters of safety model we need to use in order to guarantee the maximum level of safety.

Diss. Linköping : Univ., 2004.

Thesis (M.S.P.H.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 45 pages. Includes bibliographical references.

Orientador: Eliana Marisa Ganem / Resumo: Introdução: O parecoxibe, um pró-fármaco hidrolisado à valdecoxibe, é um antagonista da COX-2 com intensa atividade anti-inflamatória e analgésica. Embora muitos estudos tenham sido realizados indicando a eficácia dos antagonistas da COX em aliviar o processo da dor, quase nada foi estudado sobre a toxicidade desses fármacos no neuroeixo. Objetivos: O objetivo desta pesquisa foi avaliar os efeitos que diferentes doses de parecoxibe, administrado pela via subaracnoidea, em punção única, determinariam sobre a medula espinal e as meninges de coelhos. Metodologia: Após aprovação pela Comissão de Ética no Uso de Animais, 30 coelhos adultos jovens, da raça grupo genético de Botucatu, com pesos entre 2510 g e 3560 g, fornecidos pelo Biotério da Faculdade de Medicina de Botucatu, foram randomizados em três grupos: grupo S – solução salina a 0,9%, grupo P4 – parecoxibe (dose: 4 mg) e grupo P8 – parecoxibe (dose: 8 mg). Após a anestesia intravenosa com xilazina e cetamina os animais foram submetidos à punção subaracnoidea guiada por ultrassom, com agulha de Quincke 25G, no espaço entre primeira e a segunda vértebras sacrais e realizada a injeção de uma das soluções previamente sorteadas em volume de 0,4 mL (10 µL por centímetro de medula espinal medida entre a base do crânio e o espaço lombossacral). Após a recuperação da anestesia e por 21 dias, os animais foram avaliados quanto à sensibilidade e à motricidade. Em seguida, foram sacrificados por decapitação e retiradas as porções lomb... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Parecoxib, a pro-drug that is hydrolyzed to valdecoxib, is a COX-2 antagonist with strong anti-inflammatory and analgesic activity. Although many studies have demonstrated the efficacy of COX antagonists in relieving pain, almost nothing is known about the toxicity of these drugs when administered into the neuraxis. Objectives: The aim of this study was to evaluate the effects of a single injection of different doses of parecoxib into the subarachnoid space on the spinal cord and meninges of rabbits. Methods: After approval by the Ethics Committee on Animal Use, 30 young adult rabbits of the Botucatu genetic group weighing 2,510 to 3,560 g, were randomized into three groups: group S - 0.9% saline; group P4 – parecoxib (dose: 4 mg); group P8 – parecoxib (dose: 8 mg). After intravenous anesthesia with xylazine and ketamine, the animals underwent ultrasound-guided subarachnoid puncture with a Quincke 25G needle in the space between the first and second sacral vertebrae and the injection of one of the previously established solutions was performed in a volume of 0.4 mL (10 µL per cm of spinal cord measured from the skull base to the lumbosacral space). After recovery from anesthesia, the animals were evaluated regarding sensitivity and motor function for 21 days. After this period, the animals were sacrificed by decapitation and the lumbar and sacral portions of the spinal cord and the roots of the cauda equina were removed for histological examination by light micros... (Complete abstract click electronic access below) / Doutor

In this paper, I examine the impact of direct equity injections and troubled asset purchases on bank lending and solvency and analyze how ex ante tighter caps on leverage affect ex post decisions between both interventions. Extending the model of Bachmann (2018) by adding the government as a liquidity supplier, illiquid banks can either sell troubled assets at fire sale prices to collateralized financed liquid banks or to the government. If illiquid banks are forced to sell all troubled assets in order to meet premature withdrawals and the government is left with excess liquidity compared to direct equity injections, they can use these funds to bid up prices. Higher prices reduce future returns on buying illiquid assets and motivate liquid banks´ incentive to lend by crowding out their speculative motive for liquidity hoarding. As a result, troubled asset purchases weakly dominate direct equity injections in terms of lending and solvency, directly amplified by a drop in collateral liquidity. Additionally, regulating illiquid banks ex ante by tighter caps on leverage affects the government's decisions about ex post interventions to effectively stabilize lending and solvency conditions, as the self-reinforcing downward spiral between fire sale prices and collateral liquidity is mitigated. Hence, I find that there exists an inherent nexus between ex ante regulations and ex post interventions. / Series: Department of Economics Working Paper Series

Made available in DSpace on 2015-07-22T20:50:24Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-11-26 / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / Objetivo: Comparar efetividade e tolerância, a médio prazo, entre lavagem articular associada à infiltração intra-articular (IIA) com hexacetonide de triancinolona (HT) versus a IIA isolada de HT em pacientes com osteoartrite (OA) primária de joelhos. Material e Métodos: Foi realizado um estudo controlado, randomizado, duplo-cego com 60 pacientes que apresentavam OA primária de joelhos com dor em pelo menos um dos joelhos e índice de Kellgren Lawrence (KL) II e III divididos em dois grupos de intervenção: Grupo LA/HT: submetidos à LA com SF 0,9% (1000ml), finalizada pela introdução de HT 60 mg; Grupo HT: submetidos apenas à simulação de LA finalizada pela IIA de HT 60 mg. Os pacientes foram avaliados durante 12 semanas em cinco tempos de avaliação (T0, T1, T4, T8 e T12 semanas) por um avaliador “cego” através dos seguintes instrumentos de avaliação: escala visual analógica (EVA) para dor em repouso e ao movimento, goniometria, índice de WOMAC, questionário funcional de Lequesne, tempo de caminhada de 50 pés, porcentagem subjetiva de melhora, escala visual analógica de melhora (EVAM), segundo o paciente e segundo o avaliador, necessidade de anti-inflamatórios e analgésicos, número e tipo de efeitos colaterais locais. Foi realizada subanálise estatística na amostra segundo a classificação radiológica (KL II e KL III). Foi considerada uma significância estatística de 5%. Resultados: A média de idade foi de 63,7 (±8,59) anos, média de tempo de doença de 5,69 (±5,01) anos, proporção KL II/III de 33/27, sendo 88,3% de mulheres e 48,3.% de brancos. Apesar de ambos os grupos melhorarem estatisticamente na avaliação intragrupo, exceto para consumo de anti-inflamatório e EVAM, segundo o paciente, não houve diferença estatística na avaliação intergrupo para todas as variáveis estudadas no período de 12 semanas. De acordo com a subanálise realizada, observou-se, nos pacientes KL II, diferença estatística significante a favor do grupo HT para a variável flexão articular (p=0,03) no T4. Para os pacientes KL III, observou-se diferença estatística significante a favor do grupo LA/HT para as variáveis Lequesne (p=0,021) e WOMAC dor (p=0,01), assim como para a variável EVAM, segundo paciente (p=0,028) e avaliador (p=0,034) no T8. Conclusão: A combinação de LA à IIA com HT se mostrou mais efetiva a médio prazo que a IIA isolada com HT para o tratamento da OA primária de joelhos em pacientes KL III. Não houve diferença estatística quanto a tolerância destas duas intervenções. / Objective: Compare the medium-term effectiveness and tolerance intraarticular injection (IAI) with triamcinolone hexacetonide (TH) associated to joint lavage versus IAI with TH alone in patients with primary osteoarthritis (OA) of the knee. Methods: A randomized, double-blind, controlled study was carried out on 60 patients with primary OA of the knee, with pain in at least one of the knees and Grades II and III on the Kellgren-Lawrence index (KL II and III). Patients were randomized into two intervention groups: JL/TH Group – patients submitted to joint lavage with 0.9% saline solution (1000 ml) followed by a 60-mg injection of TH (3 ml); and TH Group – patients submitted to simulated joint lavage (sham) followed by a 60-mg injection of TH (3 ml). Patients were followed up for 12 weeks by a blinded observer using: visual analogue scale (VAS) for pain at rest and on movement; range of movement; Womac index; Lequesne’s questionnaire; timed 50-foot walk; subjective perception of improvement; Likert scale (0-5) for improvement assessment; the need for non-hormonal anti-inflammatory medication and analgesics; the local side effects. Results: Average age was 63.7 (± 8.59) years; mean duration of disease was 5.69 (± 5.01) years; the KL II/III proportion was 33/27; 88.3% were women and 48.3% were Caucasian. Although both groups demonstrated statistically significant improvement in the intra-group evaluation (except for Likert improvement scale according to the patient and the use of anti-inflammatory drugs), there were no statistically significant differences in the inter-group analysis for any of the variables studied over the 12-week period. In the KL II and III sub-analysis, there was a statistically significant difference regarding joint flexion among patients classified as KL II, favoring the TH group (p=0.03). For the KL III patients there were statistically significant differences favoring the JL/TH group regarding Lequesne score (p=0.021), WOMAC-pain score (p=0.01) and Likert improvement scale according to the patient (p=0.028) and the physician (p=0.034) at eight weeks. Conclusion: The combination of joint lavage and IAI with TH was more effective than IAI with TH alone in the treatment of primary OA of the knee in KL 3 patients. / TEDE / BV UNIFESP: Teses e dissertações

Durante a injeção intracitoplasmática de espermatozoides (ICSI) seleciona-se um espermatozoide móvel e morfologicamente normal para injeção em ovócito maduro. Evidências recentes indicam que mesmo espermatozoides aparentemente normais podem ocultar defeitos em nível molecular. O principal objetivo deste trabalho foi a descrição de um novo método capaz de selecionar espermatozoides maduros a partir de amostras não processadas em procedimento de ICSI. Em um estudo comparativo e prospectivo testou-se uma gota estendida modificada. A \"gota estendida com mecanismo contracorrente\" - GEMC foi montada em uma placa de ICSI padrão a partir de seis gotas de meio de cultivo (10 ?L). O posicionamento e união precisa das gotas deram origem a dois reservatórios e um canal, resultando em um fluxo de líquido através do canal. A adição de uma solução de PVP (polivinilpirrolidona) gerou um gradiente de viscosidade no final do circuito. Amostras seminais foram obtidas de 40 pacientes inférteis. Cada amostra seminal foi dividida em 4 alíquotas: uma alíquota para o processamento por centrifugação em gradiente de densidade (CGD), uma alíquota para a GEMC utilizando amostras não processadas, uma alíquota para a GEMC utilizando amostras processadas e uma alíquota para controle. Nos grupos GEMC uma média de 200 espermatozoides foram consecutivamente coletados, sem seleção, no reservatório de captura utilizando-se uma micropipeta de injeção como no procedimento convencional de ICSI. A morfologia espermática foi avaliada e demonstrou melhora, comparando-se com os controles, em todos os tratamentos utilizados. A imaturidade da cromatina foi avaliada utilizando-se o teste do azul de anilina. Em relação à imaturidade, 100% dos homens obtiveram melhores resultados tanto após o preparo por CGD quanto utilizando o método GEMC. Isto se refletiu em uma redução das formas imaturas de 28.65 ± 8.97% no sêmen fresco para 17.29 ± 7.72% após processamento por CGD (P < 0.01). Uma redução ainda maior nas formas imaturas foi obtida após o método GEMC quando comparado com o processamento por CGD: 0.89 ± 1.31% (P < 0.01) utilizando-se sêmen fresco e 1.05 ± 1.63% (P < 0.01) utilizando-se amostras processadas. Um novo método unindo seleção e captura de espermatozoides em um mesmo procedimento de ICSI foi descrito e testado. O método GEMC seleciona espermatozoides de forma fácil e permite o uso direto de amostras não processadas em procedimentos de ICSI. Este método seleciona espermatozoides maduros com mais eficiência do que o processamento por CGD. Novos estudos são necessários para se analisar o impacto do método nas taxas de fertilização, desenvolvimento embrionário, gravidez, implantação e abortamento / During intracytoplasmic sperm injection (ICSI) a motile spermatozoon with normal morphology is visually selected for insemination of an oocyte. Recent evidence indicates that even though the sperm appears morphologically normal, a possibility of defects at the molecular level still exists. The main objective of this work was to describe a novel approach capable of selecting mature spermatozoa from unprocessed semen sample in a one-step ICSI procedure. A modified extended drop was tested in a prospective comparative study. The \"Gota Estendida com Mecanismo Contracorrente - GEMC\" (Positive Rheotaxis Extended Drop - PRED) was assembled on a standard ICSI dish and consisted of six culture medium droplets (10 ?L). The precise merging of the drops created two reservoirs and a channel therefore the fluid flew through the channel. The addition of a PVP solution created a viscosity gradient in the final sector of the circuit. Semen samples were taken from 40 subfertile men. Each semen sample was divided into four aliquots: one aliquot for density gradient centrifugation (DGC), one aliquot for GEMC using fresh semen, one aliquot for GEMC using processed semen and one aliquot for the control. In GEMC a mean of 200 spermatozoa were collected consecutively, without selection, from the outlet reservoir with an injecting pipette as for conventional ICSI procedure. Sperm morphology was assessed and resulted in improvement compared to controls in all treatments. Chromatin immaturity was assessed using aniline blue assay. Regarding to chromatin immaturity, 100% of men had better results after DGC preparation and GEMC approach. This was reflected in a mean reduction from 28.65 ± 8.97% uncondensed chromatin in the native ejaculates to 17.29 ± 7.72% in DGC processed semen (P < 0.01). An even greater reduction was achieved after GEMC approach showing a mean of 0.89 ± 1.31% uncondensed chromatin compared to DGC processed sample (P < 0.01). A novel one-step ICSI approach joining sperm selection and recovery was developed and tested. This GEMC approach can select sperm easily and permits the direct use of native semen in ICSI. This approach can select sperm with lower chromatin immaturity than DGC method. Further studies need to access its relation to fertilization, embryo development, pregnancy, implantation and miscarriage rates

Background:Lower back pain is one of the most common health-related complaints in the adult population. Thirty percent of Americans 65 years and older reported symptoms of lower back pain in 2004. With an aging population, the proportion of people over the age of 65 is expected to reach 20% by the year 2030. Because of this increase in older adults, lumbar spinal stenosis (LSS) associated with arthritic changes will also likely increase. In older adults, lower back pain is most often caused by degenerative lumbar spinal stenosis. Stenosis is the narrowing ofthe spinal canal, causing pressure on the nerve roots and is frequently treated surgically. Lumbar spinal stenosis is one of the most common reasons for back surgery in patients 65 years and older 2. However, risks associated with surgery increase with age 3-5 and older patients may choose non-surgical treatment for their lower back pain, including injection treatment. Injection treatment, usually consisting of anti-inflammatory medications and analgesics, has improved since the mid-1990's when fluoroscopic guidance was developed. Information about injection treatment for lower back pain is limited, especially in the older population. An extensive review of published literature regarding injection treatment revealed a paucity of information about older adults diagnosed with lumbar spinal stenosis. In this study, three aims were designed to gain more information about the effectiveness of injection treatment in older patients with lumbar spinal stenosis. In the first (retrospective) study, information about receipt of second injections and time between injections was collected to examine injection usage. In the second and third (prospective) studies, information about pain relief and functional return following injection treatment was collected to examine the effectiveness of injection treatment in patients age 60 and older diagnosed with lumbar spinal stenosis. To our knowledge, such results have not been repolted for this population in the literature. Objective:Injection treatment is a commonly used non-surgical procedure to alleviate lower back pain in older adults. However, older patients do not have enough information about how long pain relief will last after treatment or the amount of pain relief and functional return they will experience. These studies focused on three topics: 1) usage of injection treatment; 2) effectiveness of injection treatment on pain relief; 3) effectiveness of injection treatment on functional return. In addition, the variations of the effectiveness were examined by selected patient attributes. Methods:In a retrospective study, medical records of patients aged 60 years or older from a high volume dedicated spine center at the University of Massachusetts Memorial Hospital were retrospectively reviewed. This study included those diagnosed with degenerative LSS, who had not received an injection for lower back pain within six months, and whom were treated between June I, 2006 and May 31, 2007. In two prospective studies, patients scheduled for lumbar injection treatment between January 1 and June 30, 2008 were selected from the University of Massachusetts Memorial Hospital Spine Center. Selection criteria included patients age 60 and over, diagnosed with degenerative lumbar spinal stenosis and no previous lumbar injection within 6 months or lumbar surgery within 2 years. The Pain sub-score of the SF-36 questionnaire was used to measure pain at baseline and at one and three months post injection. The Physical Component Score (PCS) of the SF-36 questionnaire and the Oswestry Disability Index (ODI) were used to measure function at baseline and at one and three months post injection. Variations in longitudinal changes in scores by patient characteristics were analyzed in both unadjusted (univariate) analyses using one-way analysis of variance (ANOVA), and adjusted (multiple regression) analyses using linear mixed effects models. Results: In the retrospective cohort, the mean age of the cohort was 68, 64% were female, 59% were married, with a mean Body Mass index of 32 kg/m2. Of 92 eligible patients, 57% returned for a second injection within six months of the first. The mean number of months between injections was 4.8 for all patients, ranging from 1 to 22 months. When patient characteristics were examined, the only variable that showed a statistically significant difference was age. Patients aged 70 years and older were found to be 67% less likely to return for a second injection when compared to patients age 60-69 (OR=0.33 (0.12 - 0.94)p In the prospective cohort, information was collected on 62 patients. Mean Pain scores improved significantly from baseline to one month (14.1 points), and from baseline to three months (8.3 points). Post injection changes in Pain scores varied by Body Mass Index (BMI) and baseline emotional health. Based on a linear mixed effects model analysis, higher baseline emotional health, as measured by the SF-36 Mental Component Score (MCS>50), was associated with greater reduction in pain over three months when compared to lower emotional health (MCS Conclusion: Patients over age 70 do not return for repeat injection as frequently as patients age 60-69. In addition, each year a patient ages over age 60, they are 10% less likely to return for a repeat injection. Lower back pain in older adults with LSS is clinically significantly alleviated after injection treatment. In addition, injection treatment for LSS is associated with return of lost function needed for daily living activities in older adults. Pain relief and functional return varies by patient personal and clinical characteristics. Higher emotional health was associated with more pain relief and more functional return experienced over three months following injection treatment. Additional information is needed about why older patients do not return for second injections at the same rate as younger patients and how emotional health affects response to injection treatment in older adults.