Thèses : « Adverse effects/therapeutic use »

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Miron, Veronique. « The effects of CNS-accessible multiple sclerosis-directed immuno-modulatory therapies on oligodendroglial lineage cells, myelin maintenance, and remyelination / ». Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115701.

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Myelin and oligodendrocytes (OLGs) are the apparent targets of the immune-mediated injury that underlies the development of multiple sclerosis (M8). Recovery from M8 clinical relapses likely reflects remyelination attributed to recruitment and differentiation of oligodendrocyte progenitor cells (OPCs), rather than to new process formation by previously myelinating OLGs. Newly emerging M8-directed immuno-modulatory therapies (statins and FTY720) can readily cross the blood-brain barrier and have been shown to impact signaling pathways implicated in cytoskeletal regulation, differentiation, migration, and survival; these are cellular events presumably important for myelin integrity and remyelination.
Statins inhibit the production of cholesterol (concentrated in the myelin membrane) and isoprenoids (post-translational attachments regulating the functions of proteins such as the Rho GTPases). We showed that treatment of human and rodent-derived OPCs with lipophilic statins induced an initial process extension associated with enhanced differentiation and impaired spontaneous migration, whereas prolonged treatment induced process retraction and cell death. Rodent and human mature OLGs demonstrated similar cytoskeletal and survival responses. Chronic simvastatin therapy of mice inhibited remyelination following demyelination induced by the OLG toxin, cuprizone, attributed to a block in OPC differentiation and consequent decrease in mature OLGs. Even fully myelinated animals treated with simvastatin over the long-term demonstrated a decrease in myelin in the brain by maintaining oligodendroglial cells in the pre-OLG state and preventing continual replacement of mature OLGs.
FTY720 is an agonist of G-protein-coupled receptors S1P1, 3, 4, and 5, that are associated with distinct receptor isotype-selective activation of Rho GTPases. In human OPCs, FTY720 could induce initial S1P3/5-dependent process retraction associated with an inhibition of differentiation, and subsequent S1P1-dependent process extension. Mature OLGs showed a dose-dependent cyclic modulation of process extension and retraction was observed over time. Both human OPCs and OLGs were rescued by FTY720 under death-promoting environments. Both cell types also demonstrated a cyclic and reciprocal modulation of S1P1 and S1P5 mRNA levels, reflected in the recurring receptor isotype-dependent functional responses over time. Studies using organotypic cerebellar slice cultures demonstrated that FTY720 did not impact myelin integrity under basal conditions, yet accelerated remyelination following lysolecithin-induced demyelination. Both treatment regimens were associated with an extension of OPC and mature OLG processes.
Our observations demonstrate that drug concentrations used to modulate immune function can have differential dose and time-dependent effects on OPCs, OLGs, as well as on myelin and remyelination processes. Our findings indicate the need to monitor the effects of putative immuno-modulatory therapies on myelin-related processes in MS patients.

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Lau, Kai-ming Eric, et 劉繼明. « Write to heal : how cognitive-change-promoting expressive writing may relieve the adverse effects of stressful lifeevents ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B37596524.

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Wilchesky, Machelle 1965. « Arrhythmia risk associated with the use of bronchodilators in patients with chronic obstructive pulmonary disease : cohort studies and methodological issues ». Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115713.

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Whereas first line therapy for chronic obstructive pulmonary disease (COPD) usually includes a short-acting bronchodilator, there are suggestions that these agents may increase the risk of cardiac arrhythmias. In this thesis, we first assessed the risks associated with short-acting beta-agonists (SABA), long-acting beta-agonists (LABA), ipratropium bromide (IB), and methyl xanthines (MX) within a cohort of COPD patients using the health databases of Saskatchewan. In order to confirm these findings and to address some methodological issues we then replicated this analysis within a larger cohort of patients using the health databases of Quebec.
Our first study cohort consisted of 6,018 adults aged 55 and older, newly treated with bronchodilator medications. We found that new users of both IB and LABA increased the risk of arrhythmia (RR 2.39 [95% CI 1.42-4.05] and (RR 4.55 [95% CI 1.43-14.45] respectively). When the cohort was restricted by excluding subjects who had recently either been hospitalised or experienced an exacerbation, the elevated risk associated with the new use of IB persisted (RR 3.65 [95% CI 1.72-7.74]), an effect was detected with new use of MX (RR 5.17 [95% CI 1.38-19.30]), but there was insufficient power to detect an effect associated with the new use of LABA.
Due to both power issues and the limited availability of LABA within the Saskatchewan data, we replicated the analysis in a larger new-user cohort of 76,661 Quebec adults aged 67 and over. This study confirmed our earlier results, with an elevated risk of arrhythmia associated with the new use of both IB and LABA (RR 1.43 [95% CI 1.08-1.88]) and (RR 1.54 [95% CI 1.00-2.36]) respectively, as well as with new use of SABA (RR 1.28 [95% CI 1.02-1.61]). Finally, using marginal structural models, we demonstrated that both exacerbations of COPD as well as minor non-event arrhythmias were moderate time-dependent confounders within this setting.
In conclusion, we found that new use of bronchodilators in COPD, particularly IB and LABA, was associated with an increase in the risk of cardiac arrhythmias. We also demonstrated the method by which the time-dependent confounder status of specific model covariates may be evaluated.

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Belfort, M. A. « The cardiovascular and cerebrovascular effects of laryngoscopy and endotracheal intubation in neonatal piglets, and the modification of these effects by topical lignocaine ». Doctoral thesis, University of Cape Town, 1990. http://hdl.handle.net/11427/26294.

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Branco, Klébia Magalhães Pereira Castello. « Análise clínica evolutiva do uso do tacrolimus como droga imunossupressora em transplante cardíaco pediátrico ». Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5131/tde-24052011-163915/.

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O Tacrolimus é uma potente droga imunossupressora introduzida no transplante cardíaco no início da década de 90. Pacientes com rejeição refratária ou intolerância à ciclosporina podem responder à terapia de resgate com o tacrolimus. Os objetivos deste estudo foram: avaliar a evolução clínica das crianças submetidas ao transplante cardíaco que necessitaram da conversão de ciclosporina para tacrolimus por rejeição refratária, tardia ou efeitos adversos de difícil controle; avaliar a incidência de rejeição após a conversão para o tacrolimus e comparar a sobrevida dos pacientes em uso de tacrolimus e ciclosporina. Realizou-se estudo coorte, observacional, prospectivo, em 28 crianças submetidas ao transplante cardíaco no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo e que foram submetidas à conversão da ciclosporina ao tacrolimus, no período de julho de 1999 a dezembro de 2009. Avaliou-se a incidência de episódios de rejeição e a sobrevida após a conversão. Realizou-se, também, a comparação entre os pacientes em uso de tacrolimus e os pacientes que permaneceram em uso de ciclosporina submetidos ao transplante cardíaco no mesmo período. A idade média no momento do transplante foi de 5,3 anos, e no momento da conversão de 8,2 anos. As causas de conversão foram efeitos adversos em 50% dos pacientes, rejeição tardia em 32% e rejeição refratária em 18%. O tempo médio de conversão e seguimento foram 36 meses e 74 meses, respectivamente. Observou-se resolução completa dos episódios de rejeição refratária e melhora dos efeitos adversos em todos os pacientes. A taxa de incidência (x100) de episódios de rejeição antes da conversão foi de 7,98 e após a conversão foi de 2,11 (p=0,0001). A taxa de episódios de infecção antes da conversão foi de 5,89 e após a conversão 4,18 (p=0,023). Pela análise das complicações pré e pós-conversão ao tacrolimus, não se evidenciou diferença estatisticamente significativa em relação a incidência de tumor, insuficiência renal, hipertensão arterial sistêmica, dislipidemia, litíase biliar, diabetes melito, anemia, alterações neurológicas, hirsutismo e hiperplasia gengival. Houve maior prevalência da doença vascular do enxerto após conversão para tacrolimus (p=0,004). Ao se comparar os pacientes com tacrolimus e os com ciclosporina, identificou-se diminuição significativa na taxa de incidência de episódios de rejeição (p=0,001), e na taxa de incidência de episódios de infecção (p=0,002), nos pacientes em uso de tacrolimus. Os pacientes convertidos ao tacrolimus apresentaram menor incidência de complicações neurológicas, hirsutismo e hiperplasia gengival, porém maior prevalência de anemia. Em relação à sobrevida, observou-se uma mortalidade de 25% nos pacientes em uso de tacrolimus, após um período médio de conversão de sessenta meses. Três óbitos foram secundários à rejeição, dos quais apenas um, no primeiro ano de transplante. Evidenciou-se menor sobrevida nos pacientes em uso de ciclosporina. O estudo clínico das crianças submetidas ao transplante cardíaco e que necessitaram de conversão do esquema de imunossupressão permitiu concluir que o tacrolimus foi eficaz como terapia de resgate para rejeição refratária e constitui opção terapêutica como droga imunossupressora de manutenção na faixa etária pediátrica
Tacrolimus is a potent calcineurin inhibitor that was introduced in heart transplantation therapy in the early 1990s. Organ transplant recipients with refractory rejection or intolerance to conventional immunosuppressant may respond to rescue therapy with tacrolimus. The aim of this study was to evaluate the clinical outcome of children undergoing heart transplantation who required conversion from a cyclosporine to a tacrolimus-based immunosuppressive regimen due to refractory rejection, late rejection or cyclosporine intolerance. We performed a prospective observational cohort study in 28 children who underwent cardiac transplantation at the Heart Institute (InCor) University of São Paulo Medical School and who required conversion from July 1999 to December 2009. The clinical outcome of the patients was evaluated after tacrolimus conversion. We also compared the patients on tacrolimus to the patients who remained on cyclosporine, and who had undergone heart transplantation during the same period. The mean age at the time of transplantation was 5.3 years and 8.2 years at the time of conversion. The causes of conversion were adverse side effects in 50% of patients, late rejection in 32% and refractory rejection in 18%. The mean time from heart transplant to conversion was 36 months and the mean follow-up period was 74 months. We observed complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (x100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (p = <0.0001). The rate of infectious episodes before conversion was 5.89 and after conversion was 4.18 (p = 0.023). There was no statistically significant difference in relation to tumor, renal failure requiring dialysis, systemic arterial hypertension, dyslipidemia, gallstones, diabetes mellitus, anemia, neurological complications, hirsutism and gingival hyperplasia after conversion. A significant incidence of cardiac allograft vasculopathy after conversion to tacrolimus was found (p = 0.004). When comparing patients on tacrolimus to patients on cyclosporine, there was a significant decrease in the incidence of rejection (p = 0.001), and infectious episodes (p = 0.002) in patients using tacrolimus. Patients converted to tacrolimus when compared to patients on cyclosporine had lower neurological complications, hirsutism and gingival hyperplasia, but higher prevalence of anemia. There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. Three deaths were secondary to rejection, and only one in the first year after transplant. Patients using tacrolimus showed greater survival rate when compared to patients taking cyclosporine. The clinical outcome of children undergoing heart transplantation and who required conversion of immunosuppressive regimen allowed us to conclude that tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option in pediatric patients

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Júnior, Otacílio de Oliveira Maia. « Efeitos do acetonido de triancinolona associado à panfotocoagulação na retinopatia diabética proliferativa ». Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5149/tde-29042008-133531/.

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INTRODUÇÃO: O tratamento padrão estabelecido pelo Early Treatment Diabetic Retinopathy Study (ETDRS) para retinopatia diabética proliferativa (RDP), com ou sem edema macular clinicamente significativo (EMCS), é a panfotocoagulação com laser. Essa forma de tratamento reduz o risco de perda visual, mas não proporciona ganho de visão. O objetivo deste estudo é avaliar os efeitos do acetonido de triancinolona associado à panfotocoagulação na RDP. MÉTODOS: Realizou-se um ensaio clínico randomizado, prospectivo e aberto com portadores de RDP bilateral e simétrica, submetidos à panfotocoagulação com laser em ambos os olhos. Portadores de EMCS foram tratados com fotocoagulação focal na região macular no primeiro episódio da panfotocoagulação. A injeção intravítrea de acetonido de triancinolona (4 mg/0,1 ml) foi administrada aleatoriamente em um dos olhos (grupo estudo), após último episódio da laserterapia, e o contralateral foi adotado para comparação (grupo controle), sendo seguidos por 6 meses. Os parâmetros adotados para avaliar os efeitos terapêuticos foram: acuidade visual com melhor correção óptica (tabela do ETDRS), medidas de espessura central e de volume macular por meio da tomografia de coerência óptica e taxa de sangramento (hemorragia pré-retiniana ou vítrea). As potenciais complicações da droga foram avaliadas durante o seguimento (pressão intra-ocular, catarata, endoftalmite e pseudo-endoftalmite). RESULTADOS: Foram incluídos 28 (vinte e oito) indivíduos com diabetes melito tipo 2. Quanto ao EMCS, 22 olhos apresentaram no grupo estudo e 23, no grupo controle (p= 0,317). A média de idade foi de 61,36 ± 5,77 anos, com predominância do sexo ferminino (57,1%). A maioria era portadora de hipertensão arterial sistêmica (82,1%) e usuária de insulina (75,0%). Não houve diferença significante nas médias de número de disparos da panfotocoagulação e da fotocoagulação na região macular entre os grupos. Quanto à acuidade visual, o grupo estudo apresentou pior acuidade antes do tratamento em relação ao grupo controle (p= 0,040), não havendo diferença significativa na primeira semana do tratamento. Durante o seguimento, o grupo estudo evoluiu com melhora na acuidade visual no primeiro (p< 0,001), no terceiro (p< 0,001) e no sexto meses (p< 0,001) em relação ao controle. Em relação às medidas de espessura central e de volume macular, os grupos não apresentaram diferença significativa antes do tratamento, no entanto, o grupo estudo apresentou medidas significativamente menores na primeira semana, no primeiro, no terceiro e no sexto meses em relação ao controle. Quanto à taxa de sangramento, 9 olhos (32,1%) do grupo controle evoluíram com sangramento e nenhum do grupo estudo (p< 0,001). Os grupos apresentaram diferença na pressão intra-ocular apenas na primeira semana do tratamento, quando as medidas do grupo estudo foram maiores que as do controle (p< 0,05). Nenhum dos olhos apresentou catarata com indicação cirúrgica, endoftalmite ou pseudo-endoftalmite. CONCLUSÃO: Os resultados deste estudo sugerem que a injeção intravítrea de triancinolona é um procedimento seguro e pode melhorar o prognóstico funcional e estrutural da mácula em olhos com RDP submetidos a panfotocoagulação com laser.
INTRODUCTION: The gold standard treatment for proliferative diabetic retinopahty (PDR) with and without clinically significant macular edema (CSME), as stablished by the Early Treatment Diabetic Retinopathy Study (ETDRS), is panretinal photocoagulation (PRP). This treatment lowers the rate of severe vision loss, but does not increase vision. The aim of this study is to evaluate the efficacy and safety of triamcinolone acetonide associated to PRP for the management of PDR. METHOD: This is a prospective, randomized clinical trial for patients with bilateral and symmetrical PDR who had undergone PRP in both eyes. Patients who had CSME were treated with macular focal photocoagulation on the first episode of the PRP. Intravitreal injection of triamcinolone acetonide (4 mg/0.1 ml) was given to the study eye after the last episode of PRP and the fellow eye was used as control. Follow up was 6 months long. Best-corrected visual acuity (BCVA) using ETDRS charts, central macular thickness and macular volume as measured by the optical coherence tomography software, and the amount of bleeding (both preretinal and vitreous) were the parameters chosen to analyse outcome. Side effects of triamcinolone acetonide such as intraocular pressure, cataracts and severe inflammation, were also followed during the study. RESULTS: Twenty eight diabetes type 2 patients were included. Twenty two study eyes and 23 fellow eyes (controls) presented with CSME (p= 0.317). Mean age was 61.36 ± 5.77 years, with 57.1% females. Many patients had hypertension (82.1%) and used insulin (75.0%). There was no significant difference on the number of spots used for PRP or macular photocoagulation in between the groups. The study eyes had lower BCVA on baseline than the control eyes (p= 0.040). One week after the treatment, there was no difference on BCVA between the study and control eyes. During the follow up, the study group increased their BCVA on the first (p< 0.001), third (p< 0.001) and sixth month (p< 0.001) compared to control. Even thought there was no significant difference on central macular thickness and macular volume between groups on baseline, the study eyes had significant lower measurements on the first week and first, third and sixth months in comparison to controls. Nine control eyes (32.1%) had hemorrhages and none study eyes (p< 0.001). Injected eyes had higher intraocular pressure than controls on the first week of treatment (p< 0.05). None of the eyes developed cataracts that needed surgery, endophthalmits or severe inflammation. CONCLUSION: This study suggests intravitreal injection of triamcinolone is a safe procedure that increases funcional and anatomical prognosis of the macula in PDR eyes that underwent PRP.

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Corley, Amanda. « The use of a securement bundle to prevent peripheral intravenous catheter failure ». Thesis, Griffith University, 2022. http://hdl.handle.net/10072/413292.

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Background: Peripheral intravenous catheters (PIVCs) are the most common invasive medical device and up to 70% of hospitalised patients require one or more during their hospital stay. However, up to 69% of PIVCs fail before treatment is complete, resulting in pain and discomfort for patients from reinsertion attempts, and financial liability for healthcare institutions. Effective PIVC dressing and securement is an important nurse-led strategy to prevent PIVC complications and failure; however, the most effective way of achieving this is yet to be determined. PIVC securement bundles are a multiproduct combination consisting of a primary dressing and securement in addition to supplementary securement products to provide extra stability. Despite growing evidence that a single dressing or securement product is not effective at preventing PIVC complications and failure, there has been very limited research attention to date on the concept of a securement bundle for the prevention of PIVC failure. Aims and objectives The overarching aim of this PhD was to investigate the use of a securement bundle to reduce PIVC complications and failure. There were three objectives guiding the research: 1) describe global usage of dressing and securement products, including supplementary securements, to secure PIVCs; 2) determine associations between (a) PIVC dressing and securement products, individually and in combination, and PIVC complications, and (b) patient, PIVC, and institutional factors, and suboptimal dressing integrity; and 3) establish the feasibility of testing securement bundles to prevent PIVC complications and failure in a pilot randomised controlled trial (RCT). Design Two frameworks were used to guide this research. The Vessel Health and Preservation Framework was used to contextualise this research within the PIVC continuum of care. The methodological framework underpinning the research methods was the Canadian Critical Care Trials Group programmatic model of research. This work was informed by an integrative review of contemporaneous literature regarding medical adhesive tapes and supplementary securement products and consisted of two phases: a secondary analysis of an existing data set of PIVC insertion, maintenance, and outcome data; and a pilot RCT testing two dressing and securement bundles against standard care for the prevention of PIVC complications and failure. Phase 1 Study design: Secondary analysis of a global cross-sectional study of PIVC characteristics, management, and outcomes. Setting: 407 rural, regional, and metropolitan hospitals in 51 countries. Sample: 40,637 PIVCs in paediatric and adult patients. Measurements: Institution, PIVC, and patient-level data were collected in the parent study. Selected data were extracted from the parent study data set for the secondary analysis, specifically those focusing on PIVC dressing and securement policy and practice. Main results: Dressing and securement practices, and local hospital policy regarding dressing change frequency varied. One-fifth of dressings (21%, n = 8519) were not clean, dry, and intact. The prevalence of PIVC insertion site complications was 16% (n = 6503), with signs of phlebitis commonly observed (11.5%, n = 4587). Compared to non-bordered polyurethane dressings, sterile gauze and tape dressings were associated with fewer insertion site complications (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.50, 0.68) and better dressing integrity (OR 0.68; 95% CI 0.59, 0.77). Compared with no securement, non-sterile tape at the insertion site was associated with more site complications (OR 2.39, 95% CI 2.22, 2.57) and poorer dressing integrity (OR 1.64, 95% CI 1.51, securement combinations were associated with fewer site and dressing complications, compared with a bordered polyurethane dressing and non-sterile tape. Local PIVC guidelines advocating 4-hourly insertion site inspection (OR 0.84, 95% CI 0.72, 0.98) and dressing replacement between 1 3 days (OR 0.80, 95% CI 0.71, 0.90) were associated with better PIVC dressing integrity than those inserted prehospital (OR 1.84, 95% CI 1.52, 2.24); or with no documentation of site assessment within the last 24 hours (OR 1.63, 95% CI 1.54, 1.72); and the absence of hospital PIVC insertion and maintenance guidelines (OR 2.58, 95% CI 2.38, 2.81). Phase 2 Study design: A non-masked, single centre, three-group pilot RCT. Setting: General medical/surgical wards of a large quaternary hospital in Queensland, Australia. Sample: Adult patients requiring a PIVC for > 24 hours, who had no laboratory-confirmed positive blood culture within 24 hours of screening. Interventions: Participants were randomised into one of three groups: 1. Standard care sterile with Border 1635, 10.5 x 8.5cm, 3M, St Paul, Minnesota, USA); plus two non-H Soft Cloth Surgical Tape, 3M, St Paul, Minnesota, USA). 2. Securement bundle 1 one sterile tape strip in chevron pattern around PIVC hub and one sterile tape strip over hub (Steri- Minnesota, USA); plus Standard care 3. Securement bundle 2 Bundle 1; plus non-compression tubular bandage (Tubifast, Mölnlycke Heath Care, Belrose, Australia). Outcome measures: The primary outcome was the feasibility of conducting a fully powered definitive RCT based on a composite of eligibility, recruitment, retention, protocol fidelity, missing data, participant/staff satisfaction at insertion and removal, and the ability to provide effect estimates. Secondary outcomes included: PIVC failure, PIVC dwell time, adverse skin events, PIVC colonisation and cost. Main results: Of 109 randomised participants, 104 were included in final analyses. Feasibility outcomes were met, except for the eligibility criterion (79%) indicating that screening processes should be streamlined. Absolute PIVC failure was 38.2% (13/34) for Bundle 2, 25% (9/36) for Bundle 1, and 23.5% (8/34) for Standard care. The incidence rate ratio for PIVC failure/1000 catheter days, compared to Standard care, was 1.1 (95% CI 0.4, 2.7) and 2.1 (95% CI 0.9, 5.1) for Bundles 1 and 2, respectively. The incidence of adverse skin events, commonly bruising, was 13%. Additional securements, either non-sterile tape and/or a tubular bandage, were applied in 45% of PIVCs; however, this practice occurred more commonly in the standard care arm compared to the securement intervention arms. Conclusion: Global PIVC dressing and securement practice is associated with site complications and poor dressing integrity, both of which are highly prevalent in clinical practice. Phlebitis symptoms and poor dressing integrity are associated with the use of non-sterile tape at the PIVC insertion site, and this practice should be de-implemented. This research introduced the novel concept of securement bundles as an intervention to address current high PIVC failure rates and showed promising results, with three of the four bundles tested in a secondary analysis of a large global data set being significantly associated with fewer site complications, and two of the four associated with fewer dressing complications. Subsequent pilot testing of two securement bundles against standard care demonstrated it is feasible and safe to conduct a large definitive trial testing this intervention to address PIVC failure. Importantly, the interventions were acceptable to staff and participants. Nurses commonly apply reinforcements to PIVC dressings, the reasons for which are not clear and require further exploration. Innovative dressing and securement solutions are needed to reduce unacceptable PIVC failure rates, and securement bundles should be investigated as a matter of priority to improve patient outcomes. This doctoral research program has advanced the understanding of the role of dressing and securement in PIVC failure, demonstrated that securement bundles should be tested in a definitive trial, and has made an important contribution to addressing the pervasive problem of PIVC failure.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Nursing & Midwifery
Griffith Health
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Pessotti, Cristiane Felix Ximenes. « Estudo comparativo do uso do antiagregante plaquetário e anticoagulante oral na profilaxia de trombose em pacientes submetidos à operação cavopulmonar total com tubo extracardíaco : análise ecorcardiográfica, angiotomográfica, cintililográfica, laboratorial e clínica ». Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5156/tde-07022014-160413/.

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Estudo prospectivo e randomizado de 30 pacientes, submetidos a derivação cavopulmonar total com tubo extracardíaco. Os dados refletem o período de 2008 a 2011, com seguimento de dois anos, por meio de avaliação clínica, laboratorial, ecocardiográfica, angiotomográfica e cintilográfica. Neste estudo, procuramos comparar a eficácia do ácido acetil salicílico (AAS) e da Varfarina na profilaxia da trombose na população estudada. Para tanto, analisamos alterações nos fatores de coagulação (VII, VIII e Proteína C ); ou nos dados clínicos que predispusessem a ocorrência de trombo no pós-operatório. Além disso, no pós-operatório, após a randomização (15 pacientes randomizados para receber Varfarina, Grupo I, e 15 pacientes randomizados para receber AAS, Grupo II), estudamos a interferência da fenestração na ocorrência de trombo; alterações hemodinâmicas que pudessem contribuir com a ocorrência de trombo (fluxo lento pelo tubo extracardíaco), por meio de ecocardiograma transesofágico realizado com até 10 dias de pós operatório, 3, 6, 12 e 24 meses de pós operatório. A presença do fenômeno tromboembólico era pesquisada, além dos ecocardiogramas acima citados, por meio de consultas clínicas realizadas com a mesma periodicidade e que avaliavam, ainda, efeitos colaterais ou complicações no uso de cada uma das drogas. Avaliamos também a viabilidade e aderência ao uso de cada uma delas. O seguimento contou igualmente com a realização de angiotomografia aos 6, 12 e 24 meses de pós-operatório para avaliação de alterações na parede interna do tubo, bem como trombos e cintilografia pulmonar, ventilação-perfusão para avaliar possível tromboembolismo pulmonar. Durante o seguimento, ocorreram dois óbitos, ambos no grupo em uso de Varfarina. Ao todo, durante os dois anos de seguimento, 33,3% dos pacientes apresentaram fenômeno tromboembólico. Sendo que, entre os paciente em uso de AAS, 46,7% apresentaram tal complicação e 20% entre os pacientes em uso de Varfarina (p=0,121). Com relação a avaliação pré-operatória, a ocorrência prévia de trombo e baixos níveis de proteína C da coagulação foram os únicos fatores que influenciaram no tempo de sobrevida livre de trombo, com valores de p de 0,035 e 0,047 respectivamente. Ao final de dois anos de seguimento, na avaliação angiotomográfica, 35,7% dos pacientes em uso de AAS tinham material hiper-refringente depositado em tubo extracardíaco com espessura superior a 2mm ( p= 0,082). Já na avaliação por cintilografia de ventilação-perfusão, dois pacientes apresentaram sinais de tromboembolismo pulmonar, ambos em uso de AAS (p=0,483), e um deles com evolução desfavorável do circuito tipo Fontan. Com relação a segurança e aderência ao tratamento, cinco pacientes tiveram dificuldade de aderência (só viabilizada por tratar-se de protocolo de estudo), entre eles, quatro em uso de Varfarina e apresentando INR variando de 1 a 6,4. Para comprovação numérica, com força estatística dos dados encontrados, uma força tarefa deve ocorrer para que se consiga um grupo maior de pacientes incluídos neste estudo. No entanto, a diferença entre os dois grupos na evolução livre de trombo nos dois primeiros anos de pós-operatório não pode, e nem deve, ser ignorada
Prospective randomized trial of 30 patients who had undergone total cavopulmonary anastomosis via an extracardiac conduit. The data reflect the period between 2008 and 2011, with two-year follow-up, through clinical, laboratorial, echocardiographic, angiotomographic, and scintigraphic assessment. In this study, we aimed to compare the efficiency of ASA (Aspirin) and Warfarin in the preventive treatment of thrombosis in the tried population. For such, we\'ve analyzed changes in coagulation factors (VII, VIII and Protein C) or in the clinical data which would predispose the occurrence of postoperative thrombus. Moreover, during postoperative care, after randomization (15 patients randomly selected to be trated with Warfarin, referred to as Group I, and 15 patients randomly selected to be treated with ASA, referred to as Group II), we also studied the influence of fenestration in the occurrence of thrombus; hemodynamic variations which could contribute to the occurrence of thrombus (slow blood flow in the extracardiac conduit), with postoperative transesophageal echocardiogram being performed within 10 days, and thereafter 3, 6, 12 and 24 months. Besides the echocardiograms aforementioned, the presence of thromboembolic events was sought after by clinical appointments taking place with the same frequency, which evaluated, apart from thromboembolism, side effects or complications from the usage of each of the drugs. We\'ve also evaluated the compliance to and feasibility of each of them. Postoperative angiotomography was also performed during the follow-up, within 6, 12 and 24 months, for the evaluation of changes on the inside wall of the extracardiac conduit, as well as thrombi, and pulmonary ventilation/perfusion scintigraphy for assessment of pulmonary thromboembolism possibility. During the follow-up, two deaths were registered, both in the group being treated with Warfarin. Overall, in the two-year follow-up, 33,3% of the patients presented thromboembolic events. Among the group being treated with ASA, 46,7% presented such complication, whereas in the group being treated with Warfarin, 20% had the same complication (p=0,121). Regarding the preoperative evaluation, prior occurrence of thrombus and low levels of coagulation factor Protein C were the only variables which influenced living time without thrombus, with p-values of 0,035 and 0,047. At the end of the two-year follow-up, in the angiotomographic evaluation, 35,7% of patients treated with ASA presented material accumulation inside the extracardiac conduit, with over 2mm of thickness (p=0,082). As for the ventilation/perfusion scintigraphy, two patients presented traces of pulmonary thromboembolism, both treated with ASA (p=0,483), one of whom with unfavorable development of the Fontan circuit. Concerning safety and compliance to the treatment, five patients had difficulty to comply with the treatment (only viable for its trial nature), among those, four under treatment with Warfarin and presenting INR values ranging from 1 to 6,4. For quantitative verification, providing statistic value to the data, an effort must be made for a larger number of patients to be gathered and tried with this treatment. However, the difference in results concerning thrombus-free recovery between the two groups during the two years following surgery cannot, and must not, be ignored

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Sauer, Herbert. « Tratamento transureteroscópico do cálculo ureteral com HOLMIUM : YAG laser ». Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-19032007-104915/.

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Objetivo: O Holmium:YAG laser é o método de litotripsia intracorpórea para cálculos urinários mais recentemente introduzido em nosso meio. O objetivo deste estudo é analisar a eficácia e as complicações imediatas do tratamento de pacientes com cálculos ureterais com essa fonte de energia. Casuística e Métodos: Foram tratados 16 pacientes, nove homens e sete mulheres, portadores de cálculos ureterais sintomáticos, maiores ou iguais a 6 mm, ou com evolução superior a 30 dias. A média de idade foi 42 anos (6- 68 anos). Quatro cálculos estavam localizados no ureter superior, seis no ureter médio e seis no ureter inferior. A técnica empregada foi a de vaporização do cálculo com Holmium:YAG laser, através de ureteroscopia. Utilizou-se exclusivamente ureteroscópio semi-rígido de 7 Fr. Resultados: A taxa de sucesso obtida foi de 87,5%, sem diferença estatisticamente significativa em relação ao relatado na literatura. Todos os cálculos foram fragmentados. Os dois insucessos da série ocorreram com cálculos localizados em ureter superior, em que fragmentos foram deslocados para o rim. As complicações observadas foram três perfurações ureterais e dois casos de febre. Conclusão: O Holmium:YAG laser é eficaz no tratamento endoscópico do cálculo ureteral. Medidas destinadas a prevenir a migração retrógrada do cálculo ou de seus fragmentos devem ser tomadas, principalmente no tratamento dos cálculos localizados em ureter superior. A litotripsia com Holmium:YAG laser não é, entretanto, um método isento de complicações, particularmente no que se refere ao tratamento de cálculos impactados de ureter superior.
Objetive: Holmium:YAG laser is the more recently method of intracorporeal lithotripsy of urinary calculi introduced in our area. The purpose of this study is to analyze the technique and to evaluate the immediate results and complications in the treatment of patients with ureteral calculi. Casuistry and Methods: Sixteen patients were treated, nine men and seven women, carrying symptomatic ureteral stones, bigger than 6 mm or with evolution superior to 30 days. The average age was 42 years old (6-88 years old). Four stones were localized in upper ureter, six in middle ureter, and six in lower ureter. The technique employed was the vaporization of the stone with Holmium:YAG laser, through ureteroscopy. It was used exclusively 7-Fr semirigid ureteroscope. Results: The rate of success attained was of 87.5%, with no statistically significant differences regarding the reports in literature. All the stones were fragmented. The two failures of the series occurred with stones localized in upper ureter, in which fragments were displaced to kidney. The complications observed were three ureteral perforations and two fever cases. Conclusion: Holmium:YAG laser is effective in the endoscopic treatment of ureteral stones. Measures aimed at preventing retrograde migration of stones or fragments should be taken, mainly when the stone are located in the upper ureter. However, lithotripsy with Holmium:YAG laser may be associated with complications, particularly in what concerns the treatment of impacted stones.

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Szabó, Zoltán. « Diabetes and coronary surgery : metabolic and clinical studies on diabetic patients after coronary surgery with special reference to cardiac metabolism and high-dose GIK / ». Linköping : Univ, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-5219.

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Carneiro, Renata Valente. « Uso de acitretina para prevenção e tratamento de câncer de pele em transplantados renais : avaliação clínica, histológica e imuno-histoquímica ». Universidade de São Paulo, 2003. http://www.teses.usp.br/teses/disponiveis/5/5133/tde-19042007-091241/.

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Os doentes transplantados renais têm alto risco para desenvolver queratoses actínicas e câncer de pele. Para verificar o efeito quimioprofilático da acitretina estudamos a evolução de 13 doentes transplantados renais com queratoses actínicas múltiplas e história de carcinomas cutâneos submetidos a tratamento por 12 meses (20mg/dia). Fez-se a avaliação clínica e laboratorial regularmente em todo o período do estudo. Realizou-se exame histopatológico, demonstração imuno-histoquímica de sub-populações de linfócitos T (CD4, CD8), células natural killer e células de Langerhans, sua quantificação e comparação em biopsias de pele, sem lesão, de área exposta e protegida do sol antes, após seis e 12 meses de tratamento. Observou-se melhora das lesões cutâneas e ausência de aparecimento de novos tumores em 12 dos 13 pacientes. Não ocorreram alterações laboratoriais relacionadas a função renal, hepatotoxicicidade e hiperlipidemia. Não houve diferenças significativas histopatológicas e da população de linfócitos T e células natural killer da pele exposta e protegida do sol com o tratamento. Verificou-se aumento numérico de células de Langerhans epidérmicas aos 12 meses quando comparado aos da pele antes e após seis meses de tratamento (p = 0,002 e p = 0,003). Em nossa casuística o uso de acitretina em doses baixas foi útil para melhorar o aspecto cutâneo e prevenir lesões cutâneas pré-cancerosas e carcinomas. O aumento das células de Langerhans epidérmicas estaria relacionado ao efeito imunomodular da acitretina.
Renal transplant recipients have an increased incidence of actinic keratosis and skin cancer. In order to examine the chemoprophylatic effects of low-dose acitretin on skin cancer development we submitted 13 renal transplanted patients to acitretin therapy (20 mg/day) for 12 month. The patients were assessed at monthly intervals during the first 6 months and every two months until the 12th month for new skin lesions and for acitretin toxicity. Normal skin biopsies of sun exposed and sun protected area were taken for histopathological exam and submitted to immunohistochemistry technique to demonstrate CD4+ and CD8+ T lymphocytes, natural killer cells and Langerhans cells wich were counted and compared in the beginning, after 6th month and 12th month of the treatment. There was an improvement of actinic keratosis and all patients but one did not develop new skin cancer. Side-effects were well-tolerated and no significant biochemical effects were observed. Although there were no differences in the microscopic aspects of the skin and in the number of CD4+ and CD8+ T lymphocytes and natural killer cells, there was a significant increase in the number of epidermal Langerhans cells after 12 months of acitretin therapy. The data obtained permit us to conclude that low dose acitretin therapy is safe, well-tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients. The increase in epidermal Langerhans cells observed may be an expression of the immunomodulatory effect of acitretin.

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Júnior, Altamiro Ribeiro Dias. « Efeitos das terapêuticas com estrogênios eqüinos conjugados ou raloxifeno sobre a rigidez arterial em mulheres na menopausa ». Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5139/tde-03102014-143049/.

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INTRODUÇÃO: A rigidez arterial é fator de risco cardiovascular pouco estudado e importante determinante de sobrecarga cardiovascular, estando associada ao envelhecimento. Analisou-se a ação das terapêuticas com estrogênios eqüinos conjugados (EEC) ou raloxifeno sobre os índices de rigidez, com o intuito de se observar a influência destas medicações na rigidez arterial, bem como se as mesmas são capazes de influenciar o envelhecimento vascular bem sucedido. MÉTODOS: Realizou-se estudo duplo cego, randomizado, placebo-controlado, que envolveu sessenta e sete mulheres saudáveis, normotensas e com 1 a 10 anos de menopausa, divididas em três grupos de 24, 25 e 18 mulheres. Estas receberam placebo, 0,625 mg EEC ou 60 mg de raloxifeno, respectivamente, 1 comprimido por dia, por 4 meses consecutivos. Analisou-se a rigidez arterial, através da avaliação das velocidades de onda de pulso carótida-femoral (VOP CF), fêmoro-pediosa (VOP FP), e do índice de amplificação (IA) da pressão sistólica na artéria carótida. RESULTADOS: Não se observou qualquer alteração dos índices de rigidez arterial associada às intervenções farmacológicas no grupo placebo (VOP CF pré x pós: 644 x 626 cm/s, p= 0,09; VOP FP pré x pós: 1006 x 1012 cm/s, p= 0,77; IA pré x pós = 30 x 29%, p= 0,55), no grupo EEC (VOP CF pré x pós: 642 x 600 cm/s, p= 0,11; VOP FP pré x pós: 952 x 971 cm/s, p= 0,66; IA pré x pós: 25 x 32%, p= 0,82) e no grupo raloxifeno (VOP CF pré x pós: 636 x 601 cm/s, p= 0,12; VOP FP pré x pós: 964 x 941 cm/s, p= 0,62; IA pré x pós:25 x 25%, p= 0,65). Apesar da ausência de ação das drogas sobre a rigidez arterial, houve uma correlação significativa entre o grau de rigidez arterial basal e a resposta à intervenção farmacológica, particularmente no grupo EEC, de tal maneira que a redução dos índices de rigidez neste grupo foi proporcional ao nível de rigidez basal, apresentando as seguintes relações: VOP CF (r= -0,602, p= 0,001); VOP FP (r= -0,455, p= 0,022); IA (r= -0,410, p= 0,042). CONCLUSÃO: EEC e raloxifeno não parecem afetar a rigidez arterial de mulheres sadias e normotensas com menos de 10 anos de menopausa
INTRODUCTION: Arterial stiffness has been recognized as a cardiovascular risk factor, an important determinant of the left ventricular overload and a marker of cardiovascular aging. However, the clinical impact of arterial stiffness and how it is affected by hormone therapy has not been fully investigated. This study analyzed the influence of conjugated equine estrogens (CEE) or raloxifene on arterial stiffness and how the may influence successful cardiovascular aging. METHODS: Sixty-seven healthy and normotensive women with 1 to 10 years of menopause were randomly assigned to one of three groups, with 24, 25, and 18 participants. They were given oral placebo, 0,625 mg of conjugated equine estrogen, or 60 mg of raloxifene, respectively, for 4 consecutive months. Arterial stiffness was evaluated by measurement of the carotid-femoral pulse wave velocity (PWV CF) and femoral-dorsalis pedis pulse wave velocity (PWV FP), and the systolic pressure augmentation index (AI) at the carotid artery obtained by applanation tonometry. RESULTS: None of the treatment regimens affected arterial stiffness: placebo (PWV CF before x after: 644 x 626 cm/s, p= 0.09; PWV FP before x after : 1006 x 1012 cm/s, p= 0.77; AI before x after = 30 x 29%, p= 0.55), CEE (PWV CF before x after: 642 x 600 cm/s, p= 0.11; PWV FP before x after: 952 x 971 cm/s, p= 0.66; AI before x after: 25 x 32%, p= 0.82) and raloxifene (PWV CF before x after: 636 x 601 cm/s, p= 0.12; PWV FP before x after: 964 x 941 cm/s, p= 0.62; AI before x afer:25 x 25%, p= 0.65). Despite the absence of statistically significant reduction in arterial stiffness with treatment, there was a significant correlation between basal stiffness and the degree of reduction in the indexes measured, indicating that the higher the basal stiffness, the greater the degree of reduction, particularly in the CEE group: PWV CF (r= -0.602, p= 0.001); PWV FP (r= -0.455, p= 0.022); AI (r= -0.410, p= 0.042). CONCLUSIONS: Conjugated equine estrogen and raloxifene do not seem to affect arterial stiffness of healthy normotensive women with less than 10 years of menopause

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Socher, Jan Alessandro. « Impacto da mitomicina-C tópica na deposição de colágeno em torno de enxerto de gordura na prega vogal de coelhos : estudo histológico e morfométrico ». Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5143/tde-01062009-113259/.

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Desde o início de 1990, a enxertia de gordura na prega vocal é descrita como um método para reparar a insuficiência glótica. O objetivo deste estudo é avaliar os efeitos da aplicação tópica de mitomicina-C no processo cicatricial de enxertos autólogos de gorduras inseridos em pregas vocais de coelhos através da medida da deposição de colágeno. Vinte e oito coelhos foram submetidos a enxertia de gordura em ambas pregas vocais. As pregas vocais direitas recebeu previamente a aplicação tópica de mitomicina-C (0,4mg/ml) durante cinco minutos enquanto que as pregas vocais esquerdas formavam o grupo controle (sem mitomicina-C). Quatro grupos com 6 coelhos cada foram sacrificados com 7, 14, 30 e 90 dias após a cirurgia de enxertia. As pregas vocais foram removidas para estudo histológico com a intenção de quantificar a deposição de colágeno através da coloração por Picrossírius Red sob microscopia polarizada. A deposição de colágeno foi menor em todos os grupos de pregas vocais que receberam aplicação tópica de mitomicina-C quando comparada com as pregas vocais do grupo controle. No presente estudo, a aplicação tópica de mitomicina-C antes da enxertia de gordura reduziu significativamente a deposição de colágeno (p = 0,05).
Since the early 1990s, fat implantation in the vocal fold is described as a method of repairing glottal insufficiency. The aim of this study was to evaluate the effect of topical application of mitomycin in the healing process with collagen deposition measurement around of autologous fat implants inserted in rabbits vocal folds. Twenty-eight rabbits were submitted to a fat implant in the both vocal folds. The right vocal folds received previously topical application of mitomycin (0,4mg/ml) for five minutes and the left vocal folds were the control group (without mitomycin). Four groups of 6 rabbits each were sacrificed 7, 14, 30 and 90 days after the implantation. The samples of the vocal folds were collected for histological analysis with the purpose of quantifying the collagen deposition by Picrosirius Red stain under polarization microscopy. The collagen deposition was lower in all groups of vocal folds with topical application of mitomycin than in control groups. In the present study, the topical application of mitomycin before the fat grafts reduced significantly the collagen deposition (p = 0,05).

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Vesna, Mijatović. « Procena kardiološke bezbednosti pri primeni metadona u supstitucionoj terapiji zavisnika od opijata ». Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2014. http://www.cris.uns.ac.rs/record.jsf?recordId=87273&source=NDLTD&language=en.

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Metadon je sintetski agonist opijatnih receptora koji se primenjuje u sklopu supstitucione terapije opijatnih zavisnika metadonom (STM) i u terapiji hroničnog bola. Dugoročna primena STM je praćena blagim, uglavnom prolaznim, neželjenim delovanjima. Međutim, metadon pripada grupi lekova koji mogu da prouzrokuju prolongaciju korigovanog QT intervala (QTc) u elektrokardiogramu (EKG-u) i povećaju rizik za nastanak potencijalno fatalnih aritmija tipa torsades de pointes. Opijatni zavisnici metadon najčešće koriste u kombinaciji sa benzodiazepinima, i ova kombinacija lekova predstavlja faktor rizika za nastanak smrtnog ishoda. Iako je najveći broj lekara upoznat sa rizikom za razvoj respiratorne depresije prilikom primene opijata u kombinacji sa benzodiazepinima, velika studija otkriva da su ventrikularne aritmije i srčani zastoj najčešće prijavljivana neželjena delovanja metadona, primenjenog u kombinaciji sa benzodiazepinima. Ciljevi ovoga radu su da se analizom smrtnih slučajeva povezanih sa upotrebom metadona (MRDs) tokom desetogodišnjeg perioda na teritoriji Vojvodine i sprovođenjem kliničkog ispitivanja kod opijatnih zavisnika na STM proceni kardiološka bezbednost primene metadona, posebno u kombinaciji sa benzodiazepinima. Sprovedena je retrospektivna studija za određivanje karakteristika MRDs na teritoriji Vojvodine, kao i kliničko ispitivanje u kome su učestvovali opijatni zavisnici koji počinju sa STM. Snimanje EKG-a (za izračunavanje QTc intervala) i uzorkovanje krvi (za određivanje koncentracije metadona i diazepama i vrednosti troponina) je sprovedeno kod svih učesnika istraživanja u 5 vremenskih tačaka (pre početka primene STM, 8. i 15. dana i nakon 1. i 6. meseca primene STM). Koncentracije metadona i diazepama u serumu su određivane metodom tečne hromatografije sa masenom spektrometrijom (LC-MS). U Vojvodini je zapažena rastuća tendencija MRDs, ali ni jedan od umrlih nije bio na STM, i najverovatnije su samoinicijativno koristili metadon i benzodiazepine. Patohistološki nalaz na srcu može govoriti u prilog kardiotoksičnosti metadona i njegove kombinacije sa benzodiazepinima, pogotovo kod slučajeva sa pronađenim akutnim miokardijalnim oštećenjem. Što se tiče hroničnih promena na srcu, ne postoji mogućnosti da se potvrdi niti opovrgne uloga psihostimulanasa. Detektovane koncentracije metadona i diazepama kod MRDs su bile u opsegu terapijskih (<1 μg/ml). Poredeći socio-demografske karakteristike opijatnih zavisnika koji su počeli sa STM u ovom istraživanju sa podacima iz sličnih studija sprovedenih širom sveta, zapažena je sličnost u pogledu velikog broja karakteristika. Srednje doze metadona 8., 15. dana i nakon 1. i 6. meseca primene STM su bile 40,23±17,11 mg, 47,11±16,79 mg, 50,00±17,55 mg i 78,63±18,14 mg, dok su srednje doze diazepama u istim vremenskim tačkama bile 35,92±10,47 mg, 33,89±9,23 mg, 28,33±11,55 mg i 28,12±11,67 mg. Srednje koncentracije metadona su u posmatranim tačkama ispitivanja iznosile 153,44±111,51 ng/ml, 157,43±112,39 ng/ml, 176,77±118,56 ng/ml i 342,86±181,54 ng/ml, dok su srednje koncentracije diazepama bile 923,00±537,89 ng/ml, 923,76±739,96 ng/ml, 560,74±436,72 ng/ml i 1045,32±932,72 ng/ml. Dužina QTc intervala pre primene STM je bila 411,87±27,22 ms, tj. 414,64±29,38 ms 8. dana STM, 416,97±26,39 15. dana, i 425,20±17,71 ms nakon 1. meseca tj. 423,50±14,72 ms nakon 6. meseca primene STM. Pokazan je statistički značajan porast dužine QTc intervala nakon 1. i nakon 6. meseca primene STM u odnosu na vrednost pre primene STM, kako u grupi svih ispitanika, tako i u podgrupi muškog pola. Pokazano je postojanje statistički značajne korelacije između koncentracije metadona i dužine QTc intervala nakon 15. dana, 1. i 6. meseca primene STM, kako kod svih ispitanika, tako i u podgrupi muškog pola. Ova korelacija ostaje statistički značajna i ukoliko se uključe i drugi faktori – koncentracija diazepama i dužina perioda upotrebe heroina, kod svih ispitanika i u podgrupi muškog pola nakon 15 dana i mesec dana primene STM, kao i u podgrupi muškog pola nakon 6. meseca STM. Iako nijedan pacijent nije prijavio neko neželjeno delovanje metadona na nivou kardiovaskularnog sistema, najveći broj pacijenata oba pola se nakon prvog meseca primene STM žalio na pojačano znojenje i opstipaciju. Koncentracije metadona i diazepama u uzorcima krvi kod MRDs se nalaze u rasponu koncentracija ovih lekova u krvi ispitanika koji su učestvovali u prospektivnoj studiji. Trećina umrlih je imala samo znake akutnog oštećenja srca, dok do porasta troponina i vrednosti QTc intervala preko 500 ms nije došlo ni kod jednog ispitanika iz prospektivne studije. Potrebno je sprovesti dalja istraživanja sa ciljem razjašnjenja moguće uloge benzodiazepina u povećanju kardiotoksičnosti metadona kod opijatnih zavisnika na STM.
Methadone is a synthetic agonist of opioid receptors which is used in methadone maintenance tratment (MMT) of opiate addicts as well as in the treatment of chronic pain. A long-term use of MMT is followed by mild, mostly transient, adverse effects. However, methadone belongs to a group of medicines which can provoke a prolongation of QTc (corrected QT) interval in electrocardiogram (ECG) and thus increase the risk from the development of potentially fatal arrhythmias – torsades de pointes. Moreover, methadone is widely associated with benzodiazepines use in heroin addicts, and this combination is considered as a risk factor for lethal outcome. Despite the fact that most of health care professionals are aware of possible respiratory depressant effect of methadone and benzodiazepines co-administration, recently published data reveal that ventricular arrhythmia and cardiac arrest are currently the most frequent adverse event attributed to methadone and benzodiazepine co-medication. The aim of this study is to assess cardiac safety of methadone use, especially in combination with benzodiazepines, by analyzing characteristics of methadone-related deaths (MRDs) during 10-year period as well as by conducting a clinical trial among opiate addicts in MMT. A retrospective study to determine the characteristics of MRDs in Vojvodina, as well as a clinical trial in which participated opiate addicts at the start of MMT were performed. ECG (to calculate QTc interval) and blood sampling (to determine methadone and diazepam concentrations and troponin values) were performed in all study participants at five time points (before the introduction of MMT, on 8th, on 15th day, after 1 and 6 months of MMT). Methadone and diazepam concentrations in serum were determined by using liquid chromatography-mass spectrometry (LC-MS). An increasing tendency of MRDs was observed in the region of Vojvodina, but none of the victims were under healthcare professionals’ control, and, most commonly, they used methadone and benzodiazepines, on their own initiative. Pathohistological findings in the heart in MRDs might support cardiac adverse effects of methadone and its combination with benzodiazepines, especially in cases with acute myocardial damage. As for the chronic heart changes, we can neither confirm nor exclude the role of psychostimulants. Detected concentrations of methadone and diazepam were in therapeutic range (<1 μg/ml). Comparing socio-demographic characteristics of opiate addicts who started with MMT in this study with data from similar studies conducted worldwide, the similarity in terms of large number of features was observed. The mean methadone dose on the 8th, 15th days, and after 1 and 6 months of MMT was 40.23±17.11 mg, 47.11±16.79 mg, 50.00±17.55 mg and 78.63±18.14 mg, respectively, while the mean diazepam dose at the same time points was 35.92±10.47 mg, 33.89±9.23 mg, 28.33±11.55 mg and 28.12±11.67 mg, respectively. The mean methadone concentration at observed time points was 153.44±111.51 ng/ml, 157.43±112.39 ng/ml, 176.77±118.56 ng/ml and 342.86±181.54 ng/ml, respectively, while the mean diazepam concentration was 923.00±537.89 ng/ml, 923.76±739.96 ng/ml, 560.74±436.72 ng/ml and 1045.32±932.72 ng/ml, respectively. The length of QTc interval before the introduction of MMT was 411.87±27.22 ms, 414.64±29.38 ms on the 8th day of MMT, 416.97±26.39 on the 15th day of MMT, after 1 month of MMT 425.20±17.71 ms and after 6 months of MMT 423.50±14.72 ms. There was a statistically significant increase in the length of QTc interval after 1 and 6 months of MMT in comparison to the value before the application of MMT, within the whole group of patients and in the subgroup of men. A statistically significant correlation between the concentration of methadone and QTc interval length after 15 days, 1 and 6 months of MMT, both in the whole group and in the subroup of men was observed. The correlation remained statistically significant if the other factors, such as concentration of diazepam and the length of heroin use, were included, in all patients and in the subgroup of men after 15 days and one month of MMT as well as in the subgroup of men after 6 months of MMT. Although none of the patients reported any cardiac adverse effect of methadone, the majority of them complained of sweating and constipation after the first month of MMT. Concentrations of methadone and diazepam in blood samples in MRDs were within the range of concentrations of these drugs in blood of patients who participated in the prospective study. In one third of MRDs only signs of acute myocardial damage were detected, while an increase in troponin values and the length of QTc interval over 500 ms did not occur in any patient in the prospective study. Further studies could clarify the possible role of benzodiazepines in the increasing cardiotoxicity of methadone in opiate addicts in MMT.

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Hillert, Lena. « Hypersensitivity to electricity : symptoms, risk factors and therapeutic interventions / ». Stockholm : Karolinska Univ. Press, 2001. http://diss.kib.ki.se/2001/91-7349-016-4/.

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Wyrwoll, Caitlin Sarah. « Adverse developmental programming of the adult phenotype by fetal glucocorticoid excess and its prevention by postnatal dietary Omega-3 fatty acids ». University of Western Australia. School of Anatomy and Human Biology, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0164.

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[Truncated abstract] Increased incidence of hypertension, insulin resistance, obesity and dyslipidemia, collectively referred to as the metabolic syndrome, has been linked to low birth weight, an indicator of a poor fetal environment. This association reflects developmental programming, a process by which organ systems are affected during early development such that disease states are more likely to emerge in adult life. Fetal glucocorticoid overexposure is thought to be a key factor that mediates developmental programming. Accordingly, maternal treatment with the synthetic glucocorticoid dexamethasone retards fetal growth and leads to delayed puberty, hypertension, hyperinsulinemia, and hyperleptinemia, either with or without increased adiposity, in adult offspring. Importantly, the postnatal environment can either amplify or attenuate the long-term outcome of developmental programming. The focus of this thesis was whether adverse developmental programming outcomes can be attenuated by the postnatal environment and thus provide therapeutic potential. Specifically, the effects of a postnatal diet rich in omega-3 fatty acids on glucocorticoid-induced developmental programming outcomes was investigated. ... The adipocyte phenotype was examined in Study 6, with hyperleptinaemia evident in offspring at 6 and 12 months of age in dexamethasone-exposed animals on a standard omega-3 diet, but this effect was prevented by a high omega-3 diet. The pattern of plasma leptin was paralleled by changes in leptin mRNA in retroperitoneal fat. Similarly, plasma levels of the inflammatory markers IL-6 and IL-1β were upregulated by prenatal glucocorticoid exposure and these were attenuated by postnatal dietary omega-3 fatty acids. Overall, omega-3 ingestion reduced adiposity, as indicated by measures of body composition. In conclusion, the studies presented in this thesis demonstrate for the first time that many of the detrimental effects of excess glucocorticoid exposure in utero on the adult phenotype can be attenuated by a postnatal diet rich in omega-3 fatty acids. This beneficial effect of omega-3 fatty acids was associated with a reversal of some (e.g. adiposal leptin) but not all (e.g. renal GR) 'programmed' changes in gene expression. These findings raise the possibility that dietary supplementation with omega-3 fatty acids may provide a viable therapeutic option for preventing and/or reducing adverse programming outcomes in humans.

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Wiegleb, Edström Desiree. « Long-wave ultraviolet radiation (UVA1) and visible light : therapeutic and adverse effects in human skin / ». Stockholm : [Karolinska Univ. Press], 2001. http://diss.kib.ki.se/2001/91-7349-003-2/.

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余詩德 et Sze-tak Yu. « Effects of Chinese green tea and tea catechins on lipolysis ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31969677.

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Wong, Sze-wan Emily, et 黃詩韻. « Vascular effects of the intravenous anaesthetic dexmedetomidine ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46925612.

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Xiang, Hong. « Effects of myo-inositol and, or triiodothyronine (T₃) treatment on cardiac dysfunction and elevated myocardial lipid levels in STZ-diabetic rats ». Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26675.

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A number of experimental studies have implied a link between diabetes-induced lipid accumulation in the myocardium and the development of cardiomyopathy. Since diabetics excrete large amounts of myo-inositol which is a lipotropic agent, this study was undertaken to investigate the effects of myo-inositol on the elevated myocardial lipid levels and the depressed cardiac performance of diabetic rats. Diabetes was induced in female Wistar rats (190-215 g) with streptozotocin (STZ) (55 mg/kg, i.v.). Three days after diabetes induction, myo-inositol was administered in the drinking water (2.5 g/kg/day) for a 8 week period. Untreated diabetics exhibited a loss of body weight, hyperglycemia, hypoinsulinemia and hypothyroidism. These effects were not altered after myo-inositol treatment. STZ-diabetes also produced a significant elevation of plasma and myocardial triacylglycerol, cholesterol and phospholipid. Myo-inositol treatment decreased these lipid levels. In addition, hearts from diabetic animals had a decreased ability to develop left ventricular developed pressure (LVDP) and both the rate of pressure rise (+dP/dt) and the rate of pressure decline (-dP/dt) were also reduced. Hearts from myo-inositol-treated diabetic animals showed a partial but definite improvement of cardiac function. As diabetes-induced hypothyroidism was not altered after myo-inositol supplementation, a combination treatment of both myo-inositol (2.5 g/kg/day, p.o. daily) and T₃ (30 ug/kg/day, s.c. daily) was then undertaken to determine whether heart function of diabetic rats could be further improved. STZ-diabetic rats were characterized by a loss of body weight, hyperglycemia and hypoinsulinemia; none of which were altered by either T₃ or myo-inositol plusT₃ treatment. T₃ treatment normalized the thyroid state of diabetic animals as shown by Tahiliani and McNeill (1984). However, plasma and myocardial triacylglycerol, cholesterol and phospholipid levels of diabetic rats either remained elevated or were further increased with T₃ or myo-inositol plus T₃ treatment. In addition, T₃ treatment alone did not prevent cardiac dysfunction in diabetic rats. There was, however, some improvement in heart function in the groups treated with both myo-inositol and T₃, but the improvement was not as pronounced as with myo-inositol treatment alone.
Pharmaceutical Sciences, Faculty of
Graduate

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Stapleton, Graham Neil. « A study of the effects of sucralfate in the bile duct litigated pig peptic ulcer model with particular reference to the effects on the physico-chemical properties of gastric mucus and including comparisons with famotidine and misoprostol ». Master's thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/25727.

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Sucralfate is a drug that effectively heals duodenal, gastric and oesophageal ulcers. It is not absorbed systemically and it has been shown to act locally by coating the ulcer base. However when it was also shown to prevent stress ulcers and ethanolinduced gastric mucosa! lesions, it seemed likely that it acted in some way to improve the effectiveness of the gastric mucosa! barrier. Some investigators suggested that it did so by stimulating local prostaglandin release. The Slomiany group, on the basis of in vitro work on the effects of Sucralfate on pig gastric mucus, claimed that Sucralfate acted by altering the physico-chemical properties of mucus to increase the viscosity and retard the back diffusion of H+ ions. The work described in this dissertation set out to verify, in vivo, these claimed effects on mucus, using an experimental porcine model of peptic ulceration, the bile duct ligated pig. In addition, the effects of Sucralfate were compared with those of Famotidine and Misoprostol, and changes in mucous prostaglandins, gastric juice pepsin and gastric flora were sought. By way of introduction, the known and postulated actions of Sucralfate, current understanding of gastric mucus physiology and pathogenesis of peptic ulceration, have been reviewed, as have experimental animal models of peptic ulceration, in order to justify using the bile duct ligated pig model.

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Kerr, Daniel Paul. « The use of acupuncture in physiotherapy practice and its efficacy in the management of low back pain ». Thesis, University of Ulster, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342533.

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Chen, Xiaoyu. « Investigation of liposomes and liposomal gel for prolonging the therapeutic effects of pharmaceutical ingredients ». HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1524.

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Cheung, Chat-pan Kenneth, et 張質彬. « The effects of berberine on hepatocellular carcinoma ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44661757.

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Hedberg, Andrew Robert. « The effects of fluorides on oral microorganisms ». Master's thesis, Faculty of Dentistry, 1987. http://hdl.handle.net/2123/4786.

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This work was digitised and made available on open access by the University of Sydney, Faculty of Dentistry and Sydney eScholarship . It may only be used for the purposes of research and study. Where possible, the Faculty will try to notify the author of this work. If you have any inquiries or issues regarding this work being made available please contact the Sydney eScholarship Repository Coordinator - ses@library.usyd.edu.au

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Dib, Ricardo Anuar. « Avaliação de sintomas e lesões esôfago-gastroduodenais secundários ao uso de antiinflamatórios ». Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-08112013-110643/.

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Introdução: Os antiinflamatórios não esteróides (AINEs), incluindo a aspirina, são drogas largamente utilizadas para tratamento das doenças inflamatórias e da dor, e que podem causar efeitos colaterais sérios, causando considerável morbidade e mortalidade, relacionadas á doença ulcerosa, duodenal e gástrica, particularmente ao sangramento gastrointestinal. O risco relativo global de complicações gastroduodenais é de três a dez vezes, maior nos usuários de AINEs, quando comparado com indivíduos sadios. Cerca de 25% dos usuários crônicos dos antiinflamatórios não esteroides (AINEs) deverão desenvolver doença ulcerosa, e de 2 a 4% deverão apresentar sangramento ou perfuração. Mais de 17.000.000 de norte americanos utilizam vários tipos de drogas antiinflamatórios não esteróides (AINEs) diariamente e que provocam mais de 100.000 hospitalizações e cerca de 7000 a 10.000 mortes por ano nos Estados Unidos da América do Norte, fazendo desta família de drogas uma das mais comumente usadas em todo planeta. Cerca de 50% das lesões observadas em endoscopias de controle, ocorrem sem que o paciente tenha qualquer tipo de sintoma. Acredita-se que houve recrudescimento da prevalência de lesões digestivas pela substituição dos antiinflamatórios COX-2 pelos antiinflamatórios tradicionais, principalmente pela ausência de cuidados na prevenção deste tipo de ocorrência, em populações consideradas de risco. Objetivos: a) avaliar a prevalência de lesões e complicações digestivas secundárias ao uso de AINEs; b) qual é o perfil clínico deste paciente atendido em razão de queixas digestivas e a relação destas com os achados endoscópicos. Materiais e métodos: estudo aberto, prospectivo, multicêntrico avaliando consecutivamente 1.231 pacientes submetidos a exame de endoscopia digestiva alta em virtude de queixas digestivas, única ou associadas, como: 1) pirose; 2) dor epigástrica; 3) dor abdominal; 4) náusea; 5) vômito. Antes da realização do exame de endoscopia digestiva alta, os pacientes respondiam a questionário cujo objetivo era avaliar o início e o tipo de queixa clínica, o uso de medicamentos e possíveis complicações associadas como sangramento digestivo. Os critérios de inclusão foram: pacientes de ambos os sexos com idade mínima de 18 anos e que tivessem sintomas prévios iniciados, no máximo, há 14 dias antes da realização do exame de endoscopia digestiva alta. Os critérios de exclusão foram os de pacientes que se recusaram a participar do estudo e/ou de assinar o Termo de Consentimento Livre e Esclarecido, os incapazes de responder ao questionário, os com idade inferior aos 18 anos, os pacientes que já haviam realizado cirurgia gástrica e pacientes portadores de insuficiência renal ou hepática. Resultados: Foram avaliados 1.213 pacientes de 18 a 82 anos sendo que 65% destes eram do sexo feminino, 13,1% eram fumantes e 15,6% referiam ingestão de bebidas alcoólicas. A utilização de AINEs foi mais frequente no sexo feminino, porém número de complicações foi maior nos pacientes do sexo masculino (sangramentos foi duas vezes maior; p=0,045 e a ocorrência de úlcera quase 1,5 vezes maior; p=0,041). Os principais sinais e sintomas relatados foram epigastralgia e pirose (67% e 62%, respectivamente). Os 1.213 pacientes foram alocados em dois grupos: Grupo I - AINE composto por 228 (18,8%) e o Grupo II - Não AINEs (NAINEs) por 985 (81,2%) pacientes.. O exame de endoscopia digestiva alta foi normal em 3,9% dos pacientes do grupo I e em 10,7% dos do grupo II (p< 0,001). A probabilidade de um paciente que não utiliza AINE ter endoscopia digestiva alta normal é 2,5 vezes maior quando comparado aos que utilizaram AINEs (p=0,001). As presenças de lesões erosivas ou ulceradas no estômago e duodeno também foram mais frequentes nos pacientes do Grupo I quando comparado aos do Grupo II. Observa-se que é maior a incidência de lesões, tanto erosivas quanto ulceradas no estômago quando comparadas ao duodeno (erosões: 49,12% vs 13,60 respectivamente, p=0,001; úlceras: 14,04% vs 11,84% respectivamente, p= 0,05). O risco de hemorragia digestiva, 12 vezes maior (6,14% vs 0,51%) nos pacientes que fizeram uso de AINEs sendo o estômago o sítio de maior prevalência de sangramento. Não se observou diferença estatística quando analisada a presença de esofagite erosiva nos dois grupos. Conclusões: Evidenciamos frequência maior de úlcera gástrica, úlcera duodenal e sangramento digestivo nos pacientes que utilizaram AINEs. Não foram encontradas relações entre os achados endoscópicos e os sintomas dispépticos. Não observamos influência dos AINEs no aparecimento de esofagite erosiva
Introduction: The non steroidal anti-inflammatory drugs (NSAID), including aspirin, are drugs widely used in the treatment of inflammatory diseases and pain. This use may cause serious side-effects, leading to considerable morbidity and mortality related to ulcer, duodenal and gastric disease, especially gastrointestinal bleeding. The overall relative risk of gastroduodenal complications is three to ten times higher in users of NSAID, compared to healthy individuals. Around 25% of the chronic users of non steroidal anti-inflammatory drugs (NSAID) will develop ulcer disease, and 2 to 4% will present bleeding or perforation. More than 17,000,000 North Americans use several kinds of non steroidal anti-inflammatory drugs (NSAID) on a daily basis. This causes more than 100,000 hospitalizations and from 7,000 to 10,000 deaths every year in the USA, which makes this drug one of the most commonly used on the planet. About 50% of the lesions observed in endoscopies occur without any kind of symptom. It is believed that there was an increase in the prevalence of digestive lesions due to the replacement of COX-2 anti-inflammatory drugs with traditional anti-inflammatory drugs, especially because of the lack of preventive care of this kind of occurrence in at-risk populations. Goals: a) Evaluate the prevalence of lesions and digestive complications, secondary to the use of NSAID; b) Evaluate the clinical profile of the patient seen for digestive complaints and the relation of these complaints with the endoscopic findings. Materials and Methods: Prospective, multi-centric, open study, evaluating consecutively 1,231 patients who underwent upper gastrointestinal endoscopy exam due to digestive complaints in isolation or associated, such as: 1) pyrosis; 2) epigastric pain; 3) abdominal pain; 4) nausea; 5) vomiting. Before performing the exam of upper gastrointestinal endoscopy, patients answered a questionnaire whose goal was to evaluate the onset and kind of clinical complaint, the use of medication and possible complications associated to digestive bleeding. The inclusion criteria were: Patients of both sexes with the minimum age of 18 and whose symptoms had begun up to 14 days before undergoing the upper gastrointestinal endoscopy. Exclusion criteria: patients who refused to participate in the study and/ or who refused to sign the Informed Consent Term, the ones who were unable to respond to the questionnaire, the ones who were under 18 years old, patients who had undergone a previous gastric surgery and patients with kidney or hepatic failure. Results: 1,213 patients with ages ranging from 18-82 were evaluated, 65% of which were female and 13,1% were smokers, 15,6% mentioned they ingested alcoholic beverages. The use of NSAID was more frequent among females. However, the number of complications was higher among males (bleeding occurred twice as much; p=0,045 and the occurrence of ulcer was almost 1,5 times higher; p=0,041). The main signs and symptoms reported were epigastralgia and pyrosis (67% and 62%). The 1,213 patients were divided into two groups: Group I- NSAID, made up by 228 (18,8%) and Group II- Non NSAID, made up by 985 patients (81,2%). The upper gastrointestinal endoscopy was normal in 3,9% of the patients in Group I and in 10,7% of the patients in Group II (p<0,001). A patient who does not use NSAID will be 2,5 times more likely to have normal upper gastrointestinal endoscopy than the one who used NSAID (p=0,001). The presence of erosive or ulcer lesions in the stomach and duodenum was more frequent in Group I patients when compared to those of Group II. It is observed that the incidence of lesions in the stomach, both erosive and ulcer is higher when compared to the duodenum (erosions: 49,12% vs. 13,60, p=0,001; ulcers: 14,04% vs. 11,84, p= 0,05). The risk of digestive bleeding is 12 times higher (6,14% vs. 0,51%) in patients who used NSAID, and the stomach is the site with higher prevalence of bleeding. No statistic difference was observed when the presence of erosive esophagitis in both groups was analyzed. Conclusions: We observed that the frequency of gastric ulcer, duodenal ulcer and digestive bleeding was higher in patients who used NSAID. Relations between the endoscopic findings and the dyspeptic symptoms were not found. The influence of NSAIDs on the appearance of erosive esophagitis was not observed

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Zhang, Xiao, et 張瀟. « The effects of l-tetrahydropalmatine and rhynchophylline, alkaloids derived from herbal medicines, on cellular and molecular neurotoxicityof cocaine in PC12 cells ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43572248.

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Faghihi, Shahabeddin. « Effects of crystal size and orientation of novel titanium-based substrates on cell adhesion : implication for medical implants ». Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111882.

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The high performance of bone implants depends on the positive response of osteoblasts to the surface of the materials manufactured for the implant. Cell response in turn strongly depends on the nature of the initial interaction of macromolecules involved in cell adhesion and proliferation with the atomic structure of the surface of the material used for the implant. The initial interaction between bone specific extracellular matrix proteins and the solid substrate influences cell response at the cell-implant interface. This interaction is crucial for implant stability, long-term durability, and osseointegration. Despite extensive research undertaken to develop high-quality material for implants in order to improve the cell-substrate interaction, little is known about the significance of the atomic structure of the substrate and the role of molecular machinery involved in cell-substrate interaction. Using a combined approach involving material sciences and cell and molecular biology, the objectives of this research are to evaluate the response of pre-osteoblast and fibroblast cell lines to novel bulk polycrystalline and single crystal titanium based material and assess the role of crystal size and orientation.
Novel bulk nano-structured titanium substrates were produced by the process of high-pressure torsion (HPT). These materials have a significant advantage compared to conventional titanium-based materials by having higher surface wettablity, mechanical properties as well as a distinct surface oxide layer and atomic structure. A co-culture system was adapted to investigate the differential response of pre-osteoblast and fibroblast cell lines to titanium and titanium dioxide single-crystal substrates.
The results of this study provide clear evidence that crystal size and specific crystallographic orientation can be used to improve cell adhesion and proliferation. The nanostructured titanium substrates show strong interaction with pre-osteoblast cells as evident by the higher expression of fibronectin and the formation of extensive focal adhesion. Differential cell behaviour of pre-osteoblasts and fibroblasts are observed in cultures grown on the substrates with specific crystallographic orientations. The degree of cell attachment of the pre-osteoblasts is considerably higher on Ti-(1120) crystal face compared with the fibroblasts. These findings have profound implications for the improved osseointegration and inhibition of fibrosis leading to long-term implant consolidation and stability.

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Vezmar, Marko. « Pharmacological effects of quinoline-related compounds in human tumour cells overexpressing the multidrug resistance protein (MRP) ». Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0003/MQ37175.pdf.

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Chan, Chung-ling Pansy, et 陳鍾靈. « The long-term effects of yoga and aerobic exercise on cognitive function and clinical symptoms in early psychosis : a follow-up randomized control trial ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206585.

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Background: A study of the impact of yoga and aerobic exercise and psychosis was conducted in 2012 by Lin et al., from The University of Hong Kong. The study indicated significant improvement in the aspects of physical fitness, cognitive functions, psychosocial and emotional functioning in patients with psychosis after a 12-week yoga or aerobic intervention program. Long-term effect of exercise intervention, however, had yet been determined. The aim of the present study was to evaluate the long-term effects of yoga and aerobic exercise on cognitive functioning and clinical symptoms in early psychosis. Patients who originally participated in Lin et al.’s 2012 study were recruited and re-assessed in this current 18-month follow-up study. Methods: Two intervention groups (yoga and aerobic exercise group) and one control group (wait-list control group) of a total 57 subjects from the initial study were recruited in this follow-up study. Cognitive functioning and clinical symptoms were assessed at three time points (T1:Baseline, T2:12-week, T3:18-month). Results: No significant changes or significant deterioration were found in cognitive functioning, clinical symptoms and depression between T2 (12-week) and T3 (18-month) in both intervention groups (yoga and aerobic group). Significant improvement of clinical symptoms was observed in wait-list control group at T3. Conclusions: Although there is no significant finding in this current study, it is still recommended that further study on the relationship between physical exercise intervention and psychosis should carried out in order to explore other adjunct, and especially low cost, treatment to antipsychotics in treating people with psychosis.
published_or_final_version
Psychological Medicine
Master
Master of Psychological Medicine

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31

Osborne, Connie M. Brajkovich (Connie Marie Brajkovich). « Brief Imagery Training : Effects on Psychological, Physiological and Neuroendocrinological Measures of Stress and Pain ». Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc277739/.

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The present study investigated the influence of a brief, intensive biofeedback-assisted imagery training regimen on psychological, physiological and neuroendocrinological measures of pain and stress in injury related chronic pain patients. The subjects were 36 patients (myelography examcandidates) who were assigned to the imagery or wait-list control group by order of referral presentation and to formulate equivalent groups.

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何禮昌 et Lai-cheong Ho. « Effects of green tea on ovariectomized rats ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970540.

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Sagar, Mohamed. « The importance of the CYP2C19 polymorphism for disposition and effects of omeprazole treatment / ». Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3624-2/.

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Cheung, Chi-leung, et 張智良. « Effects of tomato juice supplementation on the antioxidant status of Chinese adults ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B31227235.

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London, Leslie. « The health hazards of chemical use in agriculture ». Master's thesis, University of Cape Town, 1996. http://hdl.handle.net/11427/27007.

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Photocopies of journal articles. * Agrichemical safety practices on farms in the Western Cape. London L. SA Med J 1994 ; 84 : 273-278. * Notification of pesticide poisoning in the Western Cape 1987 - 1991. London L, Ehrlich R, Rafudien S, Krige F, Vurgarellis P. SA Med J 1994 ; 84 : 269-272. * Critical Issues in agrichemical safety in South Africa. London L, Myers JE. Am J Ind Med 1995 ; 27(1) : 1-14. * Repeatability and validity of a field kit for estimation of cholinesterase in whole blood. London L, Thomson ML, Sacks S, Fuller B, Bachmann OM, Myers JE. Occupational and Environmental Medicine 1995; 52 : 57-64. * Biological Monitoring of workers exposed to organophosphate pesticides: Guidelines for field application. London L. Occupational Health Southern Africa July/August 1995 ; 1(4) : 13-17.
Despite playing an important role in crop protection and increasing food production, chemicals used in agriculture may have a range of unanticipated effects on human health. Such effects may range from overt and acute poisonings to gradual-onset chronic morbidity. In South Africa, data on such morbidity are sparse, and subject to much underreporting as one of the included papers illustrates. The dearth of such data has much to do with the marginalised living and working conditions in agriculture and the lack of attention to occupational and environmental health on farms in the country. We have little sense of the extent of hazardous exposures in agriculture, nor of their health impacts on rural populations. Even less so, have methods for the control of poisoning by pesticides been investigated amongst farm workers in South Africa. A public health response to this problem should aim at all levels of prevention (primary, secondary and tertiary), by characterising the extent and distribution of the problems caused by pesticides, identifying risk factors and groups at highest risk for poisoning, as well as testing intervention strategies and technologies. The set of papers presented below attempts to do that by linking a series of investigations into different aspects of agrichemical hazards in South Africa, with a focus on the Western Cape. The first paper examined various aspects of potential exposure to agrichemicals on farms in the Stellenbosch region, taking into account both environmental and occupational routes of exposure. The second paper describes the profile of agrichemical poisoning in the province from 1987 to 1991, identifying high risk groups and characterising the completeness and nature of reported poisonings. The third paper developed from the author's growing realisation of the need to contextualise problems related to agrichemical exposures and effects within the overall legislative and public health framework in South Africa. This paper therefore identifies the key public health issues that need addressing with regard to pesticide safety. Finally, the last two papers address aspects related to workplace interventions for the prevention of agrichemical poisoning. One paper deals with the evaluation of a field kit (for validity and repeatability) for monitoring workers exposed to organophosphate and carbamate insecticides, while the last paper elaborates guidelines for the use of cholinesterase testing in the primary and secondary prevention of organophosphate and carbamate poisoning. In this series, therefore, the papers attempt to address the problem of agrichemical hazards within a public health framework, tracing the problem from potential exposure to acute outcomes, through reviewing the legislative and occupational health environments, through to technologies and policy guidelines related to workplace intervention. In doing so, the papers use the term "agrichemical" to refer to all chemicals used in agriculture for pest and weed control. This supersedes the term "pesticide" which has ambiguous meanings in the technical environment. Readers are therefore advised to understand the term "agrichemical" to include the generic aspects of chemical usage on crops in agriculture. The research on which these papers was based was spawned by the involvement of the author in a larger research project investigating long-term neurobehavioural effects of organophosphate exposure on deciduous fruit farm workers over the period 1991 - 1994. This latter piece of research is not referred to here as it was the basis for another degree at the University of Cape Town.

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Chan, Wing-yan Veronica, et 陳詠恩. « An examination of neuroprotective effects of 17B-estradiol and extracts from Panax Quinquefolius L., Ginkgo Biloba and HypericumPerforatum against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)induced nigral-striatal neuronal degeneration ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B3122720X.

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Fu, Xiuqiong. « A study on the involvement of TLR4/STAT3 signaling in the antimelanoma effects of atractylenolide II /Fu Xiuqiong ». HKBU Institutional Repository, 2017. http://repository.hkbu.edu.hk/etd_oa/370.

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Melanoma is the leading cause of skin cancer-related death. The STAT3 (signal transducer and activator of transcription 3) and TLR4 (toll-like receptor 4) signaling pathways have been shown to be activated in melanoma. Activation of each of the two pathways can promote melanoma growth, angiogenesis and metastasis. Suppressing TLR4 signaling or STAT3 signaling has been proposed as an approach for melanoma management although the TLR4/STAT3 pathway has not yet been established in melanoma. Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), a Qi-tonifying Chinese medicinal herb, is commonly prescribed by Chinese medicine doctors for treating melanoma. Our previous studies demonstrated that atractylenolide II (AT-II), isolated from Atractylodis Macrocephalae Rhizoma, could induce apoptosis, and inhibit proliferation and migration in B16 melanoma cells. However, the antimelanoma properties of AT-II and the underlying molecular mechanisms have not been fully understood. In this study, we further investigated the antimelanoma effects of AT-II in vivo and in vitro, and explored the TLR4/STAT3 signaling-related mechanism of action of AT-II. In conclusion, we established the TLR4/STAT3 pathway in melanoma, which provides novel insight into melanoma pathophysiology. We demonstrated that AT-II exerted antimelanoma effects in vivo and in vitro, and inhibition of TLR4/STAT3 signaling contributed to these effects. These findings advanced our understanding of the antimelanoma properties and the underlying mechanism of action of AT-II, and provided a chemical and pharmacological justification for the clinical application of Atractylodis Macrocephalae Rhizoma in melanoma management. This contribution is significant because it is one step in a continuum of research that is expected to lead to future clinical trials of AT-II as a novel antimelanoma agent. Results showed that AT-II induced apoptosis, and inhibited proliferation, migration and invasion in multiple melanoma cells, and significantly inhibited melanoma growth, angiogenesis and metastasis in mice. AT-II suppressed the activation of STAT3 and Src (a STAT3 upstream tyrosine kinase) in mouse melanoma tissues and inhibited the EGFR/Src/STAT3 signaling in cultured melanoma cells. The free binding energy of AT-II with EGFR (an upstream receptor tyrosine kinase of STAT3) was relatively low in molecular docking assays, suggesting that AT-II might inhibit EGFR activation via other molecules. We found that activation of TLR4 enhanced EGFR/Src/STAT3 signaling in melanoma cells, and activation of the TLR4/STAT3 pathway contributed to melanoma progression in vivo and in vitro. These observations suggested that the TLR4/STAT3 pathway was established in melanoma. Molecular docking showed that AT-II could bind to the TLR4/MD-2 receptor complex. AT-II reduced the binding of LPS (a TLR4 ligand) to TLR4, and inhibited LPS-triggered activation of EGFR/Src/STAT3 signaling as well as LPS or MPLAs (synthetic monophosphoryl lipid A, a TLR4 agonist) induced invasion in melanoma cells. Overexpression of a constitutively active variant of STAT3 (STAT3C) in A375 cells diminished anti-proliferative, apoptotic and anti-invasive effects of AT-II; and overexpression of an active form of TLR4 in A375 cells diminished AT-II-exerted anti-invasive effects in cultured cells, and attenuated the inhibitory effects of AT-II on tumor growth and angiogenesis in mice. These suggested that suppression of TLR4/STAT3 signaling contributed to the antimelanoma effects of AT-II.

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Tsang, Ting Fung. « Mechanistic study of Chinese herbal medicines on melanogenesis and anti-melanoma effects ». HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1506.

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Gu, Baoying. « Selective increase of neuronal cyclooxygenase-2 (COX-2) expression in vulnerable brain regions of rats with experimental Wernicke's encephalopathy : effects of nimesulide ». Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112627.

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Wernicke's encephalopathy is a neuropsychiatric disorder resulting from thiamine deficiency (TD) and is characterized by neuronal loss, astrocytic proliferation and microglial activation. Cyclooxygenases (COX) are enzymes which catalyze the first step in the synthesis of prostanoids. COX-1 is expressed constitutively and COX-2 is the inducible isoform. Groups of TD rats and pair-fed controls were killed at presymptomatic and symptomatic stages of encephalopathy. Cresyl violet and NeuN staining showed decreased numbers of neuronal cells in vulnerable regions (medial thalamus and inferior colliculus) but not in a spared region (frontal cortex). Numbers of GFAP-positive and OX-42-positive cells were increased at symptomatic stage of encephalopathy. Expression of COX-2 mRNA and neuronal COX-2 immunoreactivity were selectively increased in vulnerable regions of TD rats at symptomatic stages of encephalopathy. Nimesulide, a highly selective COX-2 inhibitor, lowered PGE2 levels and precipitated the progression of encephalopathy suggesting that COX-2 in this model is conferring neuroprotection.

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Liu, Zhongqiu. « Mechanism of pharmacokinetic interaction between paeoniflorin and sinomenine ». HKBU Institutional Repository, 2006. http://repository.hkbu.edu.hk/etd_ra/720.

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Bellows, Jennifer L. « The effects of humor on mood state of older adults ». Virtual Press, 1995. http://liblink.bsu.edu/uhtbin/catkey/941361.

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The purpose of this study was to determine if exposure to humor media improves mood states of older adults. The humor media consisted of four thirty minute videos. Ten subjects from a retirement community in East Central Indiana participated in the study. A control group and experimental group were assigned by the Activities Director of the retirement community. Each participant was administered the Profile of Mood States for the pretest and posttest measurement. The Profile of Mood States lists sixty-five adjectives and participants ranked on a scale of 0 to 4 how much they felt that mood within the past week. Members of the experimental group participated in fifteen minute interviews after the completion of the intervention.Total mood score means for the experimental group indicated an increase in positive mood from the pretest to the post-test. Total Mood Score means for the control group showed either no change or a decrease in positive mood. Because the sample size was very small,no statistical test of significance could be executed to test the null hypothesis. Based upon the qualitative interviews and the simple analysis of quantitative data humor media appears to have positive effects on the subjects in nursing homes and retirement communities. However, this intervention deserves further investigation with a larger sample that would allow for more rigorous statistical analysis.
Fisher Institute for Wellness

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42

Norda, Rut A. C. « Plasma as a Therapeutic Principle in Clinical Practice : With Special Reference to Sweden ». Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7838.

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Wang, Liangjie, et 王亮节. « Differential effects of Radix Paeoniae Rubra on cytokine and chemokineexpression inducible by mycobacterium ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44523543.

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Tsang, Hing Yan. « Anti-tumour and anti-angiogenic effects of euxanthone ». HKBU Institutional Repository, 2001. http://repository.hkbu.edu.hk/etd_ra/363.

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葉衍葳 et Aaron Yip. « Effects of Angelica sinensis extract on mucus synthesis and cell proliferation of the stomach ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31969884.

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Xiao, Haitao. « Therapeutic effects and the underlying mechanisms of qing-dai powder against experimental colitis in mice ». HKBU Institutional Repository, 2015. https://repository.hkbu.edu.hk/etd_oa/213.

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Ulcerative colitis (UC), a subset of inflammatory bowel disease (IBD), is a chronic uncontrolled inflammatory condition of the intestinal mucosa. As its etiology remains unclear, no specific effective treatment is available. Therefore, development of novel strategies for IBD treatment remains a major medical need. Qing-dai Powder (QDP), an ancient herbal medicinal formula, exerted potent therapeutic effect on intractable UC patients; however, evidence-based support is needed. The aims of this study are: i) to delineate the anti-colitis effect of QDP and its underlying mechanisms in murine colitis; 2) to explore the rationality of QDP formula; 3) to investigate the anti-colitis effects of major component(s) or/and active ingredient(s) of QDP and their underlying mechanisms in murine colitis. In the present study, the therapeutic effect of QDP on UC was investigated on dextran sulfate sodium (DSS)-induced acute murine colitis. Results showed that i) QDP dose-dependently attenuated disease activity index (DAI), colon shortening, histological damage and colonic myeloperoxidase (MPO) activity of DSS-treated mice; ii) QDP significantly decreased the infiltration of immune cells, particularly macrophages and CD4+ T cells, colonic levels of pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6, and plasma level of chemokine MCP-1. In RAW 264.7 cells, QDP significantly suppressed lipopolysaccharide (LPS)-induced the production of TNF-α and IL-6, and the expression levels of COX-2 and iNOS via inhibiting IкB-α degradation and p65 nuclear translocation; Also, in primary CD4+ T cells, QDP significantly suppressed the differentiation of Th1 and Th17 cells. These findings indicate that the anti-colitis effects of QDP might be associated with inhibition of inflammatory responses of colonic macrophages and CD4+ T cells. QDP is composed of Qing-dai and Ku-fan. The comparative study of anti-colitis of QDP, Qing-dai and Ku-fan revealed that QDP is a reasonable TCM formula, and Qing-dai is mainly responsible for the anti-colitis effect of QDP and Ku-fan exhibits a weak beneficial effect. Mechanistically, it was found that Qing-dai significantly suppressed Th1 and Th17 responses, characterized as i) suppressing mRNA expression of Th1 cytokine IFN-γ and Th17 cytokine IL-17A, inhibiting the production of Th1 and Th17-related cytokines IFN-γ, IL-17A/F and TNF-α in the colon of DSS-treated mice; ii) restraining the proportions of Th1 and Th17 cells in mesenteric lymph nodes of DSS-treated mice; iii) suppressing the differentiation of Th1 and Th17 cells in vitro. Indirubin is the principle active component of Qing-dai. It was found that indirubin significantly suppressed the generation of Th17 cells in DSS-treated mice, evidenced by i) suppressing the mRNA expression of IFN-γ, IL-17A, and RORγt, and inhibiting the production of IL-17A/F, TNF-α, IL-1β and IL-6 in the colon of DSS-treated mice; ii) reducing Th17 cells in mesenteric lymph nodes of DSS-treated mice through reducing GSK-3β activity and p-STAT3 expression; iii) suppressing the differentiation of Th17 cells through down-regulating the expression of GSK-3β and p-STAT3 in vitro. In summary, the present study provides evidence-based support for the clinical use of QDP in the management of UC, and indicates that indirubin is the main active compound of QDP responsible for its anti-colitis effect.

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Li, Hongying, et 李洪英. « Secondary degeneration after partial optic nerve transection : mechanisms and the neuroprotective effects of lycium barbarum ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/197129.

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Glaucoma is a neurodegenerative disease and one of the major causes of blindness in the world. Secondary degeneration is involved in glaucoma. The retinal ganglion cells (RGCs) which are vulnerable to secondary degeneration in glaucoma are the promising target population for therapeutic intervention. Partial optic nerve transection (PONT) model has been established in the last decade. Primary and secondary degeneration can be separated in different regions of retinas in this model. Therefore, PONT is a good model for the study of mechanisms of secondary degeneration and the drug screening for secondary degeneration. Lycium barbarum (L. barbarum) has been shown to be neuroprotective for cortical neurons in vitro. It has also been shown that L. barbarum could delay RGCs death in a rat ocular hypertension model. In order to further investigate the effects of L. barbarum for RGCs, two models, complete optic nerve transaction (CONT) model and PONT model, were employed in my study. My results showed that the polysaccharide extract from L. barbarum (LBP) could partly prevent RGCs from death in the inferior retinas 4 weeks after PONT whereas it could not reduce the loss of RGCs after CONT. The1,1'-dioctadecyl-3, 3, 3’, 3’-tetramethylindocarbocyanine perchlorate(DiI) labeling of RGCs whose axons were transected showed that the majority of labeled cell bodies existed in the superior retinas. The result meant that more cell bodies in the superior retinas would die from primary degeneration than in the inferior retina after PONT. Therefore my results indicated that LBP protected RGCs which would die from secondary degeneration rather than primary degeneration. The results of Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) staining showed that RGCs underwent apoptosis 1 week after PONT. Western-blot analysis demonstrated that oxidative stress was involved in the degeneration of RGCs after PONT. Furthermore, c-Jun N-terminal kinases (JNKs) pathway was activated which was indicated by an increase ofphospho-JNK2/3(p-JNK2/3)and phospho-c-jun(p-c-jun). Our results also revealed that orally feeding of LBP could increase the expression of manganese superoxide dismutase (MnSOD) and insulin growth factor-1 (IGF-1)and decrease the expression of p-JNK2/3 and p-c-jun. The results from optic nerve (ON) study showed that glial cells, including astrocytes and microglias/macrophages, were activated after PONT. Oxidative stress and inflammation were involved in the process. Secondary degeneration of ON was not obvious and LBP exerted no protective effects on the survival of axons in the ON. The multifocal electroretinography (mfERG) study showed that both the functions of inner retinas and outer retinas were damaged after PONT. The results indicated that other cell types or the synapses between different cell types were damaged in addition to RGCs. LBP could improve the function of the whole retinas, including both inner retinas and outer retinas after PONT. In conclusion, our results indicated that LBP protected RGCs from secondary degeneration via inhibiting oxidative stress and the activation of JNK pathway.LBP could also improve the function of both inner retinas and outer retinas after PONT.
published_or_final_version
Anatomy
Doctoral
Doctor of Philosophy

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« Search for treatment strategies to enhance the cytotoxic effects of doxorubicin and mitomycin C on tumor cells and to lower their adverse side effects on the host ». 1998. http://library.cuhk.edu.hk/record=b5889691.

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by Chan Hung Chuen.
Thesis (M.Phil.)--Chinese University of Hong Kong, 1998.
Includes bibliographical references (leaves 143-151).
Abstract also in Chinese.
Acknowledgments --- p.i
Abstract --- p.ii
Abstract (Chinese version) --- p.v
Abbreviations --- p.viii
Content --- p.ix
Chapter CHAPTER ONE --- INTRODUCTION
Chapter 1. --- Free radical and free radical-mediated antitumor drugs --- p.1
Chapter 2. --- Mitomycin C (MC)
Chapter 2.1 --- Drug actions of MC --- p.2
Chapter 2.2 --- Adverse side effects of MC --- p.5
Chapter 3. --- Doxorubicin (DOX)
Chapter 3.1 --- Drug actions of DOX --- p.7
Chapter 3.2 --- Adverse side effects of DOX --- p.8
Chapter 4. --- Antioxidants --- p.14
Chapter 5. --- Effects of exogenous ATP on the antitumor activity of Doxorubicin and Mitomycin C
Chapter 5.1 --- Glutathione (GSH) and related enzymes --- p.17
Chapter 5.2 --- Glutathione (GSH) and Anticancer Quinones --- p.19
Chapter 5.3 --- Glutathione and the cardiac toxicity of the anticancer drugs --- p.20
Chapter 5.4 --- Glutathione depletion in tumor cells by exogenous ATP --- p.21
Chapter 6. --- Aim of research --- p.24
Chapter CHAPTER TWO --- THE EFFECT OF ANTIOXIDANTS ON DOXORUBICIN- OR MITOMYCIN C-INDUCED CYTOTOXICITY ON HUMAN TUMOR AND NORMAL CELL LINES
Chapter 2.1 --- Introduction --- p.26
Chapter 2.2 --- Materials and Methods --- p.28
Chapter 2.3 --- Results --- p.36
Chapter 2.4 --- Discussion --- p.60
Chapter CHAPTER THREE --- STUDY OF CARDIOPROTECTIVE EFFECTS OF ANTIOXIDANTS AGAINST DOXORUBICIN- OR MITOMYCIN C-INDUCED TOXICITY BY LANGENDORFF PERFUEED ISOLATED RAT HEART MODEL
Chapter 3.1 --- Introduction --- p.64
Chapter 3.2 --- Materials and Methods --- p.67
Chapter 3.3 --- Results --- p.75
Chapter 3.4 --- Discussion --- p.76
Chapter CHAPTER FOUR --- THE EFFECT OF ANTIOXIDANTS DURING CHEMOTHERAPY OF DOXORUBICIN OR MITOMYCIN C IN TUMOR-BEARING MICE
Chapter 4.1 --- Introduction --- p.78
Chapter 4.2 --- Materials and Methods --- p.80
Chapter 4.3 --- Results --- p.83
Chapter 4.4 --- Discussion --- p.93
Chapter CHAPTER FIVE --- HISTOLOGICAL STUDY AND LIPID PEROXIDATION STUDY OF PROTECTIVE EFFECT OF ANTIOXIDANTS IN TUMOR-BEARING MICE TREATED WITH DOXORUBICIN OR MITOMYCIN C
Chapter 5.1 --- Introduction --- p.95
Chapter 5.2 --- Materials and Methods --- p.98
Chapter 5.3 --- Results --- p.103
Chapter 5.4 --- Discussion --- p.117
Chapter CHAPTER SIX --- EFFECT OF EXOGENOUS ATP ON THE ANTITUMOR ACTIVITY OF DOXORUBICIN AND MITOMYCIN C ON CULTURED HUMAN HEPATOMA CELLS
Chapter 6.1 --- Introduction --- p.122
Chapter 6.2 --- Materials and Methods --- p.124
Chapter 6.3 --- Results --- p.126
Chapter 6.4 --- Discussion --- p.136
Chapter CHAPTER SEVEN --- CONCLUSION
Chapter 7.1 --- Conclusion --- p.139
Chapter 7.2 --- Future perspective --- p.141
Bibliography --- p.142

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PETRONI, GIULIA. « Immunogenicità dei Farmaci Biologici : Analisi dei Meccanismi Fisiopatologici e Sviluppo di Test in vitro per il suo Monitoraggio ». Doctoral thesis, 2013. http://hdl.handle.net/2158/852105.

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I farmaci biologici stanno assumendo un ruolo sempre più importante per la terapia di molte patologie sia nell’ambito dell’oncologia che della medicina interna. In particolare trovano largo impiego per il trattamento di varie malattie immunomediate, quali le connettiviti, le vasculiti, le malattie infiammatorie croniche dell’intestino e la psoriasi. I farmaci biologici presentano una caratteristica propria ed in parte anche intrinseca che è quella della immunogenicità, ossia della capacità di indurre una risposta immune diretta contro il farmaco stesso. Questa risposta indesiderata che si esprime innanzitutto con la formazione di anticorpi anti-farmaco (anti-drug antibodies: ADAs), può essere di tipo transiente in assenza di qualsiasi rilevanza clinica, oppure può associarsi ad eventi clinicamente significativi quali la perdita di efficacia della proteina terapeutica o la comparsa di reazioni di ipersensibilità, talvolta fatali, al momento della somministrazioni del farmaco. L’incidenza della formazione di ADA varia notevolmente sulla base del tipo di farmaco e sul tipo di assay utilizzato per il dosaggio. La sensibilità e la specificità dei tests possono essere influenzati da vari fattori, quali la presenza di farmaco circolante nel siero che può condurre a risultati falsamente negativi. La maggior parte degli ADA appartengono all’isotipo IgG, tuttavia molto recentemente sono stati descritti anche anticorpi anti-farmaco di tipo IgE per vari anticorpi monoclonali quali cetuximab, infliximab e tocilizumab. Il progetto dello studio è stato quello di studiare sia la risposta umorale che cellulare indotte dalla terapia con farmaci biologici in soggetti affetti da malattie immunomediate. In particolare sono stati presi in esame i seguenti anticorpi monoclonali: infliximab, rituximab (entrambi anticorpi monoclonali chimerici) ed adalimumab (anticorpo monoclonale umano). Successivamente sono state effettuate correlazioni cliniche tra lo sviluppo di anticorpi anti-farmaco e la perdita di efficacia e/o comparsa di reazioni avverse, soprattutto allo scopo di poter utilizzare i suddetti assays a scopo preventivo per incrementare la safety. Durante il suo corso di Dottorato, la Dott.ssa Petroni Giulia ha appreso tecniche di coltura cellulare e di messa a punto e validazione di test ELISA durante la realizzazione del progetto di ricerca “Immunogenicità dei Farmaci Biologici: Analisi dei Meccanismi Fisiopatologici e Sviluppo di Test in vitro per il suo Monotoraggio”.

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50

« Effect of co-treatment of flavonoids with doxorubicin in chemotherapy ». 2001. http://library.cuhk.edu.hk/record=b5890755.

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Chan Ching-Man Loren.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2001.
Includes bibliographical references (leaves 126-144).
Abstracts in English and Chinese.
Acknowledgement --- p.ii
Abstract --- p.iii
Table of Content --- p.vii
List of Figure --- p.ix
List of Abbreviations --- p.xii
Chapter Chapter One --- General Introduction
Chapter 1.1 --- Doxorubicin --- p.1
Chapter 1.2 --- Antioxidants --- p.11
Chapter 1.3 --- Flavonoids --- p.17
Chapter 1.4 --- Protection against doxorubicin-induced cardiotoxicity by antioxidant --- p.25
Chapter 1.5 --- Aim of research --- p.25
Chapter Chapter Two --- Study of Cardioprotection Effect of Flavonoids Against Doxorubicin-induced Toxicity in Sprague-Dawley Rats
Chapter 2.1 --- Introduction --- p.27
Chapter 2.2 --- Materials and Methods --- p.29
Chapter 2.3 --- Results --- p.37
Chapter 2.4 --- Discussion --- p.51
Chapter ChapterThree --- Study of Effect of Flavonoids in Chemotherapy of Doxorubicinin Tumor-bearing Mice
Chapter 3.1 --- Introduction --- p.54
Chapter 3.2 --- Materials and Methods --- p.56
Chapter 3.3 --- Results --- p.63
Chapter 3.4 --- Discussion --- p.80
Chapter ChapterFour --- Study of the Effect of Flavonoids on Doxorubicin-induced Cytotoxicity on Human Tumor Cell Line and Doxorubicin-resistant Human Tumor Cell Line
Chapter 4.1 --- Introduction --- p.83
Chapter 4.2 --- Materials and Methods --- p.86
Chapter 4.3 --- Results --- p.94
Chapter 4.4 --- Discussion --- p.120
Chapter Chapter five --- Conclusion --- p.122
References --- p.126

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Thèses sur le sujet « Adverse effects/therapeutic use »

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