O câncer é uma das principais causas de morte em todo o mundo e o fator limitante na terapia antitumoral é a resistência a processos terapêuticos. Diversos são os mecanismos de resistência à drogas antitumorais e é fundamental desvendar os mecanismos envolvidos na quimiorresistência para eliminá-lo e ter-se uma melhor eficácia terapêutica. Nesse trabalho investigamos os mecanismos que determinam resistência a cisplatina em células de glioma. Primeiramente, mostramos que a resistência celular a cisplatina era independente de p53, capacidade de reparo de DNA. Utilizando modelo in vitro e in vivo foi demonstrado que os níveis de glutationa (GSH) tinha papel fundamental na resistência a cisplatina e temozolamida (TMZ). A linhagem de glioma resistente a TMZ tinha maior proteção antioxidante, maior expressão do fator de transcrição NRF2, GCLM e GST (envolvidos na geração e utilização de GSH). Utilizando modelo in vitro e in vivo mostramos que BSO (inibidor da síntese de GSH) potencializava o efeito tóxico do TMZ. Assim, a combinação de BSO com cisplatina e TMZ é uma abordagem poderosa para otimizar a citotoxicidade em tumores, sendo uma alternativa excitante para o tratamento de pacientes com glioma ou melanoma. / Cancer is one of main cause of death worldwide and the limiting factor is antitumoral therapy resistance. Several mechanisms command drug resistance and fundamental question is how is to unveil the mechanisms involved in it to get a better therapeutic efficacy. We investigated the mechanisms of cisplatin resistance in glioma cells. We demonstrated that cisplatin resistance was p53 independent and DNA repair capacity. It was demonstrated in a in vitro a in vivo model that gluthatione (GSH) is the major resistant factor for cisplatin and temozolomide (TMZ). We observed that the TMZ resistant glioma cell line counted with a high expression of the antioxidant transcription factor NFR2, GCLM and GST. We observed that NFR2 silencing greatly enhanced cell death, high levels of DNA damage upon TMZ treatment. In addition, BSO potentiated TMZ killing in human and murine melanoma using in vitro and in vivo models. Thus, combination of BSO, cisplatin and TMZ is a powerful strategy to optimize tumor killing, thus providing an exciting alternative therapeutic protocol to glioma and melanoma patients.

Bakgrund: Fler än 216 miljoner människor i världen lider av ångestsyndrom. Ångestsyndrom orsakar lidande och kan påverka patienternas liv på ett negativt sätt. Ett stort antal av Sveriges sjukskrivningar är orsakade av ångestsyndrom och ångestsyndrom påverkar också världsekonomin negativt. Tidigare forskning har visat på att fysisk aktivitet kan minska risken för hjärtsjukdomar, högt blodtryck, diabetes och osteoporos. Som sjuksköterska kan man träffa på patienter med ångestsyndrom, men även patienter med andra sjukdomar kan uttrycka ångest. Det är därför av stor vikt att ha kunskap om detta och kunna informera, erbjuda alternativa behandlingar och motivera patienterna.Syftet: Att sammanställa effekter av fysisk aktivitet hos patienter med ångestsyndrom.Metod: En litteraturstudie med innehållsanalys av 13 artiklar av kvantitativ ansats. Resultatet: Artiklarna som ligger till grund för den aktuella litteraturstudien har påvisat skiftande resultat med både goda, inga och negativa resultat. Övervägande har det framkommit goda effekter så fysisk aktivitet kan presenteras och användas som adjuvant behandling hos patienter med ångestsyndrom.Konklusion: Fysisk aktivitet har många goda effekter på människor, både fysiskt och psykiskt. Med rätt information och omvårdnad kan fysisk aktivitet användas med god effekt hos patienter med ångestsyndrom. Fysisk aktivitet i kombination med antingen läkemedel eller KBT har visat på störst effekt kring att minska ångest. Således kan fysisk aktivitet som adjuvant behandling bidra till att ångesten minskar hos dessa patienter. / Background: More than 216 million people in the world suffers from anxiety disorder. Anxiety disorder causes suffering and may affect the patients' life in a negative way. A large number of the sick leave in Sweden is caused by anxiety disorder and anxiety disorder affects the world ecomony in a negatively way. Previous research has shown that physical activity can reduce the risk of heart disease, high blood pressure, diabetes and osteoporosis. As a nurse you can encounter patients with anxiety disorder, but even patients with other diseases can express anxiety. Therefore, it is important to have knowledge of this and to be able to give information, offer alternative treatments and motivate patients. Purpose: To examine the effect of physical acitivty to patients with anxiety disorder.Method: A literatur review with content analysis of 13 articles with quantitative approach.Results: The articles underlying the current literature study have shown changing results with both good, no and negative results. Considerable, good effects have shown so physical activity can be presented and used as adjuvant therapy in patients with anxiety disorder.Conclusion: Physical activity has many good effects on people, both physically and mentally. With proper information and nursing care, physical activity can be used with good effects with patients with anxiety disorder. Physical acitivty in combination with either medication or CBT has shown the most effect to reduce anxiety. Therefore can physical activity as additional treatment contribute to reduce anxiety in these patients.

京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第22135号 / 生博第422号 / 新制||生||55(附属図書館) / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 藤田 尚志, 教授 朝長 啓造, 教授 永尾 雅哉 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is to systematically survey all adjuvant treatments after surgery investigated in rat and mouse models. Both PubMed and Embase were explored with a systematic bibliographic search algorithm. Inclusion criteria consisted of treatments applied to rats or mice after complete transection and microsurgical repair of lower-limb motor or mixed nerves. Effect size statistics enabled numerical comparison between outcomes of treated and untreated animals and ranked the best treatments. 1,553 articles were found according to our search strategies, and 22 of them corresponded to our pre-defined inclusion criteria. After data extraction and analysis, the top 3 adjuvant strategies in terms of combined average effect size were citicoline, neurotrophin-4, and nitric oxide synthesis inhibitor, with values of 5.52, 5.14 and 4.08, respectively. Definitive treatment comparison was difficult due to the lack of uniformity in outcome evaluation in the experiments performed. Animal studies, comparing treatments administered within the same experimental protocol, are needed to truly assess efficiency and to provide solid recommendations for future clinical investigation.

Surgical repair alone does not lead to satisfactory recovery after nerve laceration injury, yet no adjuvant clinical treatments are available. The goal of this review is to systematically survey all adjuvant treatments after surgery investigated in rat and mouse models. Both PubMed and Embase were explored with a systematic bibliographic search algorithm. Inclusion criteria consisted of treatments applied to rats or mice after complete transection and microsurgical repair of lower-limb motor or mixed nerves. Effect size statistics enabled numerical comparison between outcomes of treated and untreated animals and ranked the best treatments. 1,553 articles were found according to our search strategies, and 22 of them corresponded to our pre-defined inclusion criteria. After data extraction and analysis, the top 3 adjuvant strategies in terms of combined average effect size were citicoline, neurotrophin-4, and nitric oxide synthesis inhibitor, with values of 5.52, 5.14 and 4.08, respectively. Definitive treatment comparison was difficult due to the lack of uniformity in outcome evaluation in the experiments performed. Animal studies, comparing treatments administered within the same experimental protocol, are needed to truly assess efficiency and to provide solid recommendations for future clinical investigation.

The blood-brain barrier (BBB) maintains brain homeostasis by limiting entry of substances to the central nervous system through interaction of transmembrane and intracellular proteins that make up endothelial cell tight junctions (TJs). Recently it was shown that the BBB can be modulated by disease pathologies including inflammatory pain. This study examined the effects of chronic inflammatory pain on the functional and molecular integrity of the BBB. Inflammatory pain was induced by injection of complete Freund's adjuvant (CFA) into the right plantar hindpaw in female Sprague-Dawley rats under halothane anesthesia; control animals were injected with saline. Edema and hyperalgesia were assessed by plethysmography and infrared pawwithdrawal latency. At 72 h postinjection, significant edema formation and hyperalgesia were noted in the CFA-treated rats. Examination of permeability of the BBB by in situ perfusion of [14C]sucrose while rats were under pentobarbital anesthesia demonstrated that CFA treatment significantly increased brain sucrose uptake. Western blot analysis of BBB TJ proteins showed no change in expression of zonula occludens-1 (an accessory protein) or actin (a cytoskeletal protein) with CFA treatment. Expression of the transmembrane TJ proteins occludin and claudin-3 and -5 significantly changed with CFA treatment with a 60% decrease in occludin, a 450% increase in claudin-3, and a 615% increase in claudin-5 expression. This study demonstrates that during chronic inflammatory pain, alterations in BBB function are associated with changes in specific transmembrane TJ proteins.

京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第19668号 / 薬科博第56号 / 新制||薬科||7(附属図書館) / 32704 / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 髙倉 喜信, 教授 橋田 充, 教授 佐治 英郎 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Bakgrund: Depression är en av världens vanligaste sjukdomar, som över 350 miljoner människor i världen lider av. I Sverige lider fem procent av befolkningen av depression och 80 % av dessa behandlas med antidepressiva läkemedel. Alternativa åtgärder rekommenderas då läkemedelsanvändningen ökar och ofta kommer med bieffekter. Sjuksköterskan möter personer med depression överallt i vården och bör därför ha kunskap om andra åtgärder. En sådan åtgärd kan vara fysisk aktivitet. Kunskapen kan användas som incitament och omvårdnadsåtgärd. Syftet: Att undersöka effekten av fysisk aktivitet för patienter med diagnostiserad depression. Metod: Litteraturstudie med innehållsanalys av 11 artiklar med kvantitativ ansats. Resultatet: Fysisk aktivitet hade god effekt på depression, speciellt när det användes som adjuvant behandling. Intensiteten på den fysiska aktiviteten hade ingen påverkan på depressiva symtom. Slutsats: Fysisk aktivitet bör rekommenderas till personer med depression då det enligt denna studies resultat ger god effekt. / Background: Depression is one of the world’s most common diseases, that over 350 million people worldwide suffer from. In Sweden, five percent of the people suffer with depression and 80 % of them are treated with antidepressants. Alternative measures should be recommended as drug usage increases and often come with side effects. Nurses meets people with depression everywhere in healthcare and should have knowledge of other alternative measures. Such a measure could be physical activity. This knowledge can be used as incentives and nursing intervention. Purpose: To examine the effect of physical activity for patients diagnosed with depression Method: A Literature review with content analysis of 11 articles with quantitative approach. Results: Physical activity had a positive effect on depression, especially when used as an adjuvant treatment. The intensity of the physical activity had no effect on depressive symptoms. Conclusion: Physical activity should be recommended to people with depression because according to this study´s result it provides good effect on depression.

No description available.

<p>  </p> <p>The study presented within demonstrates that Nano-11, a plant-derived nanoparticle adjuvant, can be utilized in conjunction with innate immune stimulators, including the TLR3 agonist poly(I:C) and the STING agonist cyclic-di-AMP, to provoke enhanced immune responses when administered through intradermal vaccines. The study demonstrated that the utilization of a combination adjuvant consisting of Nano-11 and a synthetic STING agonist, ADU-S100, in intradermal vaccination exhibited dose-sparing characteristics and resulted in enhanced immunity in both mice and pigs when compared to intramuscular immunization. The utilization of Nano-11-based adjuvant technology has demonstrated both prophylactic and therapeutic efficacy in mouse models of lymphoma and melanoma. The proposed adjuvant platform for intradermal vaccines, which is based on Nano-11, aims to enhance the accessibility of vaccines for the purposes of controlling infectious diseases and cancers.</p>