No description available.

Cyanobacterial secondary metabolites are a rich source of bioactive compounds with potential utilization in pharmacology. The aim of this study was to evaluate the effect of the novel compound nostatin A isolated from the cyanobacterium Desmonostoc muscorum. Project was focused on the extraction, purification and characterization of the cytostatic effect caused by this novel compound and its naturally occurred structural analogues. The cytostatic activity of nostatin A and its analogs was evaluated in HeLa cell line. Experiments based on microscopy, flow cytometry and HPLC-HRMS techniques were performed in order to clarify the cytostatic effect of nostatin A in HeLa cells and its mechanism of the action.

No description available.

Câncer é uma das principais causas de mortes no mundo. Foi responsável por aproximadamente 8,2 milhões de óbitos em 2012 e estima-se 13,2 milhões de mortes em 2030, o que o posiciona como um problema de saúde pública. A quimioterapia torna-se necessária para o tratamento, pois regride o crescimento tumoral e diminui as chances de metástases, as quais são responsáveis por 90% dos óbitos decorrentes do câncer. Linhagens tumorais que apresentam alta expressão de proteínas antiapoptóticas da família Bcl-2 mostram-se resistentes à ação de quimioterápicos antineoplásicos disponíveis na terapêutica. Portanto, o desenvolvimento de compostos que inibem essas proteínas, torna-se interessante para o tratamento do câncer. A queleritrina, um alcaloide presente em diversas espécies da família Papaveraceae, representa um atraente protótipo para o desenvolvimento de inibidores de Bcl-2, visto que esta molécula apresenta atividade citotóxica por meio da inibição da Bcl-XL, proteína supressora da apoptose. Face ao exposto, o objetivo deste trabalho foi sintetizar análogos da queleritrina planejados por simplificação molecular e testar sua atividade citotóxica. A síntese dos compostos foi realizada em duas etapas, com metodologias baseadas em reações de adição nucleofílica com posterior redução. Os análogos foram caracterizados por espectroscopia de ressonância magnética nuclear (RMN) 1H e 13C, cromatografia líquida de alta eficiência (CLAE) e análise elementar (CHN). A citotoxicidade dos compostos sintetizados e da queleritrina foi avaliada por meio do método de determinação da viabilidade celular por biorredução do sal de tetrazólio (MTT) nas linhagens não-tumorigênicas HUVEC e LL24, e nas linhagens tumorais Jurkat, SK-Mel-28 e A549. Os resultados obtidos no ensaio de citotoxicidade demonstraram que os compostos sintetizados não possuem citotoxicidade significante nas concentrações testadas. Ao avaliar o potencial citostático dos compostos frente à linhagem mutirresistente A549, o composto 2f (3-OH e 4-OH) apresentou atividade antiproliferativa interessante na concentração de 75 µM. Por não apresentar toxicidade em células não tumorais, o composto 2f mostra-se mais seletivo do que seu protótipo. Estudos de modelagem molecular sugerem que a perda da planaridade da queleritrina seja o principal responsável pela diminuição da atividade biológica. Dessa forma, embora os compostos tenham apresentado propriedades biológicas diferentes da esperada, os resultados obtidos podem auxiliar no planejamento de novas moléculas com atividade e seletividade potencialmente superiores à queleritrina, representando assim, potenciais candidatos a fármacos que podem ampliar o arsenal terapêutico para o tratamento de neoplasias. / Cancer is a leading cause of death and was responsible for approximately 8.2 million of deaths in 2012 and 13.2 million of demises are estimated for 2030, which made cancer a public health problem. Chemotherapy is required for cancer treatment, because it decreases the chances of metastasis and regresses tumor growth. However, tumor cell lines which overexpress anti-apoptotic Bcl-2 proteins present resistance to most of anticancer drugs. In this context, the development of molecules with inhibitory activity against these proteins is a promising therapeutic strategy for cancer treatment. Chelerythrine, an alkaloid distributed in several species of Papaveraceae family, has shown considerable antiproliferative activity due to inhibition of Bcl-XL anti-apoptotic protein, which represents an attractive prototype to anticancer drug design. Then, the aim of this study was to synthesize chelerythrine analogues designed by molecular simplification and evaluate their cytotoxic activity. The synthetic strategy was performed into two steps, with methodologies based on nucleophilic addition reaction followed by reduction. The compounds were characterized by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, high performance liquid chromatography (HPLC) and elemental analysis (CHN). The cytotoxic activity of the analogues were evaluated through MTT assay, a colorimetric assay for assessing cell viability, against human umbilical vein endothelial cells (HUVEC) and lung fibroblasts (LL24) as non-tumorigenic cell lines, and also against tumor cell lines, such as human lymphoblastoid (Jurkat), human melanoma cells (SK-Mel-28) and carcinomic human alveolar basal epithelial cell line (A549). The compounds have not shown significant citotoxicity at the tested concentrations. However, the evaluation of cytostatic activity on multiresistant A549 cell line has demonstrated an antiproliferative potential of compound 2f (3-OH and 4-OH) at 75 µM. Since compound 2f (3-OH and 4-OH) did not show citotoxicity on non-tumorigenic cell lines, it presented higher selectivity than chelerythrine. Molecular modeling results indicate that the lack of planarity of the chelerythrine analogues might be responsible for their lower citotoxicity. Thus, it is expected that the results might help directing the design of new compounds with superior activity and more selective than chelerythrine, thereby representing potential drug candidates, which may enhance the therapeutic arsenal for cancer treatment.

No description available.

Câncer é uma das principais causas de mortes no mundo. Foi responsável por aproximadamente 8,2 milhões de óbitos em 2012 e estima-se 13,2 milhões de mortes em 2030, o que o posiciona como um problema de saúde pública. A quimioterapia torna-se necessária para o tratamento, pois regride o crescimento tumoral e diminui as chances de metástases, as quais são responsáveis por 90% dos óbitos decorrentes do câncer. Linhagens tumorais que apresentam alta expressão de proteínas antiapoptóticas da família Bcl-2 mostram-se resistentes à ação de quimioterápicos antineoplásicos disponíveis na terapêutica. Portanto, o desenvolvimento de compostos que inibem essas proteínas, torna-se interessante para o tratamento do câncer. A queleritrina, um alcaloide presente em diversas espécies da família Papaveraceae, representa um atraente protótipo para o desenvolvimento de inibidores de Bcl-2, visto que esta molécula apresenta atividade citotóxica por meio da inibição da Bcl-XL, proteína supressora da apoptose. Face ao exposto, o objetivo deste trabalho foi sintetizar análogos da queleritrina planejados por simplificação molecular e testar sua atividade citotóxica. A síntese dos compostos foi realizada em duas etapas, com metodologias baseadas em reações de adição nucleofílica com posterior redução. Os análogos foram caracterizados por espectroscopia de ressonância magnética nuclear (RMN) 1H e 13C, cromatografia líquida de alta eficiência (CLAE) e análise elementar (CHN). A citotoxicidade dos compostos sintetizados e da queleritrina foi avaliada por meio do método de determinação da viabilidade celular por biorredução do sal de tetrazólio (MTT) nas linhagens não-tumorigênicas HUVEC e LL24, e nas linhagens tumorais Jurkat, SK-Mel-28 e A549. Os resultados obtidos no ensaio de citotoxicidade demonstraram que os compostos sintetizados não possuem citotoxicidade significante nas concentrações testadas. Ao avaliar o potencial citostático dos compostos frente à linhagem mutirresistente A549, o composto 2f (3-OH e 4-OH) apresentou atividade antiproliferativa interessante na concentração de 75 µM. Por não apresentar toxicidade em células não tumorais, o composto 2f mostra-se mais seletivo do que seu protótipo. Estudos de modelagem molecular sugerem que a perda da planaridade da queleritrina seja o principal responsável pela diminuição da atividade biológica. Dessa forma, embora os compostos tenham apresentado propriedades biológicas diferentes da esperada, os resultados obtidos podem auxiliar no planejamento de novas moléculas com atividade e seletividade potencialmente superiores à queleritrina, representando assim, potenciais candidatos a fármacos que podem ampliar o arsenal terapêutico para o tratamento de neoplasias. / Cancer is a leading cause of death and was responsible for approximately 8.2 million of deaths in 2012 and 13.2 million of demises are estimated for 2030, which made cancer a public health problem. Chemotherapy is required for cancer treatment, because it decreases the chances of metastasis and regresses tumor growth. However, tumor cell lines which overexpress anti-apoptotic Bcl-2 proteins present resistance to most of anticancer drugs. In this context, the development of molecules with inhibitory activity against these proteins is a promising therapeutic strategy for cancer treatment. Chelerythrine, an alkaloid distributed in several species of Papaveraceae family, has shown considerable antiproliferative activity due to inhibition of Bcl-XL anti-apoptotic protein, which represents an attractive prototype to anticancer drug design. Then, the aim of this study was to synthesize chelerythrine analogues designed by molecular simplification and evaluate their cytotoxic activity. The synthetic strategy was performed into two steps, with methodologies based on nucleophilic addition reaction followed by reduction. The compounds were characterized by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, high performance liquid chromatography (HPLC) and elemental analysis (CHN). The cytotoxic activity of the analogues were evaluated through MTT assay, a colorimetric assay for assessing cell viability, against human umbilical vein endothelial cells (HUVEC) and lung fibroblasts (LL24) as non-tumorigenic cell lines, and also against tumor cell lines, such as human lymphoblastoid (Jurkat), human melanoma cells (SK-Mel-28) and carcinomic human alveolar basal epithelial cell line (A549). The compounds have not shown significant citotoxicity at the tested concentrations. However, the evaluation of cytostatic activity on multiresistant A549 cell line has demonstrated an antiproliferative potential of compound 2f (3-OH and 4-OH) at 75 µM. Since compound 2f (3-OH and 4-OH) did not show citotoxicity on non-tumorigenic cell lines, it presented higher selectivity than chelerythrine. Molecular modeling results indicate that the lack of planarity of the chelerythrine analogues might be responsible for their lower citotoxicity. Thus, it is expected that the results might help directing the design of new compounds with superior activity and more selective than chelerythrine, thereby representing potential drug candidates, which may enhance the therapeutic arsenal for cancer treatment.

Bakgrund: Idag erbjuder sjukhus i Sverige gruppträning som rehabilitering för cancerpatienter i syfte att minska eventuella behandlingsframkallade biverkningar. Träning kan bromsa sjukdomsförlopp, förhindra spridning av sjukdomen och minska sjukdomsrelaterad ångest och oro. Det anses vara en brist på evidens gällande cancerpatienters upplevelser kring träning i grupp som rehabiliteringsform.   Syfte: Syftet är att undersöka hur patienter med cancersjukdom upplever gruppträning, under eller efter cancerrelaterad behandling.    Metod: I en kvalitativ intervjustudie med en induktiv ansats inkluderades sex kvinnliga intervjupersoner. Det utfördes sex semistrukturerade intervjuer. Intervjuerna utfördes på patienter som tidigare har genomgått en hel gruppträningsperiod handledd av en fysioterapeut. Materialet analyserades enligt kvalitativ innehållsanalys.     Resultat: Intervjuernas innehåll delades upp i 8 underkategorier och 4 huvudkategorier. Huvudkategorierna bestod av Motivation att träna, Träningsmiljö, Hinder för träning och Upplevda positiva effekter efter avslutad träning   Slutsats: Resultatet av studien visar vikten av det sociala stödet och att det upplevdes spela en nyckelroll för intervjupersonernas trygghet och förståelse. Positiva effekter upplevdes av träningen i sig, såsom bättre styrka, kondition och högre energinivå. Författarparet identifierade att informationsbrist, brist på energi och negativa tankar kunde upplevas som centrala negativa faktorer som i sin tur kunde påverkat motivationen att träna. / Background: Hospitals in Sweden offers group exercise as a possibility for rehabilitation to patients with cancer to aim the possible side effects cancer treatment may induce. Exercise may delay, or stop, proliferation of the disease and may even reduce cancer related depression and anxiety. It is considered that it lacks evidence describing the experiences cancer patients have after using exercise as rehabilitation form.   Aim: The purpose is to investigate how patients with cancer experience group exercise, during or after completed cancer treatment.   Method: In a qualitative interview study with an inductive approach six female interview persons were included. Six semi-structured interviews were performed. The authors interviewed patients who completed a whole group exercise-period supervised by a physical therapist. The results were then analysed using a qualitative content analysis.   Result: The interview results was divided into 8 sub-categories and 4 main categories. The main categories were Exercise motivation, Exercise environment, Exercise obstacles and Experienced positive effects after completed exercise.   Conclusion: The results shows that the importance of the social environment plays a key role according to the experience of support and understanding. It was also described that physical effects from the exercise itself was present. The individuals felt both stronger and experienced having a higher energy level. The authors did identify that lack of information, lack of energy and negative thoughts were described as obstacles, these obstacles were the main negative factors that could lower the individual’s motivation towards the exercise.

Si les risques liés à la présence de résidus médicamenteux dans l'environnement sont encore méconnus, les premiers cas avérés et l'introduction récente de trois médicaments (2013) sur une liste de surveillance de l'UE imposent d'ores et déjà le développement de procédés de traitement capables d'éliminer cette pollution spécifique. C'est dans ce contexte que le traitement des effluents d'un service d'oncologie par un bioréacteur à membranes a été évalué dans cette thèse. Les effluents collectés sont caractérisés par une importante variabilité de la charge polluante et des concentrations médicamenteuses très élevées, parfois supérieures à 1 mg.L-1. Ces conditions n'ont pas favorisé le développement continu de la biomasse épuratrice. Il a toutefois été démontré que la toxicité de ces effluents n'est pas proportionnelle à la charge appliquée puisqu'une charge massique supérieure à 0.20 kgDCO.kgMVS-1.j-1 permet la croissance de la biomasse. Le colmatage des membranes a permis une rétention significative des médicaments sélectionnés. L'élimination des médicaments sélectionnés a par ailleurs été systématiquement améliorée par les boues acclimatées avec notamment le développement de capacités de biotransformation sur des molécules parfois uniquement éliminées par sorption dans les stations d'épuration. / The risks concerning the presence of pharmaceutical residues into the environment are still unknown. However, the first confirmed cases and the recent introduction of three drugs (2013) on a surveillance list of EU already require the development of processes able to remove this specific pollution. It is against that background that oncological ward wastewater treatment by a membrane bioreactor was investigated in this thesis. These effluents are characterized by a very variable charge and high pharmaceutical concentrations, sometimes above 1 mg.L-1. These conditions did not favor the continuous development of the biomass. However, it could be demonstrated that the toxicity of these effluents is not related to the applied charge since a food to microorganisms ratio above 0.20 kgCOD.kgMLVSS-1.d-1 allows biomass growth. Membrane fouling played a major role in the significant retention of the investigated drugs. In comparison to unacclimated activated sludge from WWTP pharmaceutical removal was systematically enhanced by the acclimated biomass with the development of biotransformation possibilities.

<p><strong>Bakgrund:</strong> Hand-fot syndrom är en form av perifer sensorisk neuropati orsakad av cytostatikabehandling. Syndromet kan ge biverkningar såsom smärta, obehag, domningar, svullnad och nedsatt balans. Utvärderade behandlingsmetoder saknas.</p><p><strong>Syfte:</strong> Undersöka hur tolv veckors sjukgymnastisk behandling med långvågsdiametri, interferens och balansträning påverkar biverkningar i fot/underben orsakad av cytostatikabehandling hos sju patienter med hand-fot syndrom.</p><p><strong>Metod:</strong> Gruppstudie, kvasiexperimentell resultatstudie. Sju patienter deltog. Variabler som mättes var, smärta, obehag, domningar och balans. Tre mätningar utfördes, före, efter samt åtta veckor efter interventionen. Självrapporterad skattning och fysisk mätning användes.</p><p><strong>Resultat: </strong>Gruppens smärta, obehag och domningar minskade vid samtliga mätningar. För smärta visade mätning efter intervention samt åtta veckor efter signifikans (p=0,027), (p=0,042). Obehag visade signifikans efter interventionen (p=0,018). Domningar visade ingen signifikans. Balans visade signifikans i: Skärpt Romberg, höger, blundande, åtta veckor efter interventionen (p=0,043). Skärpt Romberg, vänster, blundande, efter interventionen (p=0,027), åtta veckor efter interventionen (p=0,028). Stående på ett ben, höger, blundande, efter interventionen (p=0,042), åtta veckor efter interventionen (p=0,027). Inga mätningar visade försämringar.</p><p><strong>Slutsats: </strong>Restultaten visade att behandling med långvårdsdiametri, interferens och balansträning minskade smärta, obehag, domningar och delvis förbättrade balans vid hand-fot syndrom. Dock går det inte att påvisa vilken behandlingskomponent som påverkat mest. Ytterligare studier behövs för att ge resultat större giltighet.</p> / <p><strong>Background</strong>: Hand-foot syndrome is a form of perifier sensory neuropathy caused by chemotherapy. The syndrome can cause side effects such as pain, discomfort, numbness, swelling and impaired balance. Evaluated treatment is lacking.</p><p><strong>Purpose:</strong> Examine how twelve week physiotherapy treatment short-wave diathermy, interference and balance training affects side effects of the foot/lower leg caused by chemotherapy in seven patients with hand-foot syndrome.</p><p><strong>Method:</strong> Study group, quasi-experimental outcome study. Seven patients participated. Variables measured were, pain, discomfort, numbness, and balance. Three measurements were carried out, before, after, and eight weeks after the intervention. Self-reported estimates and the physical measurement were used. <strong></strong></p><p><strong>Results:</strong> The group's pain, discomfort and numbness decreased in all measurements. For pain measurement after the intervention and eight weeks after showed significance (p = 0,027),(p = 0,042). Discomfort showed significance after the intervention (p = 0,018). Numbness showed no significance. Balance showed significance in: Sharpened Romberg, left, eyes closed, eight weeks after intervention (p = 0,043). Sharpened Romberg, left, eyes closed, after the intervention (p = 0,027), eight weeks after intervention (p = 0,028). Standing on one leg, the right, eyes closed, after the intervention (p = 0,042), eight weeks after intervention(p = 0,027). No measurements showed deterioration.</p><p><strong>Conclusion:</strong> The results showed that treatment with short-wave diathermy, interference and balance training reduced pain, discomfort, numbness and partial improvements in balance in hand-foot syndrome. However, it is not possible to demonstrate which treatment component that affected the most. Further studies are needed to produce results more valid.</p>

Bakgrund: Hand-fot syndrom är en form av perifer sensorisk neuropati orsakad av cytostatikabehandling. Syndromet kan ge biverkningar såsom smärta, obehag, domningar, svullnad och nedsatt balans. Utvärderade behandlingsmetoder saknas. Syfte: Undersöka hur tolv veckors sjukgymnastisk behandling med långvågsdiametri, interferens och balansträning påverkar biverkningar i fot/underben orsakad av cytostatikabehandling hos sju patienter med hand-fot syndrom. Metod: Gruppstudie, kvasiexperimentell resultatstudie. Sju patienter deltog. Variabler som mättes var, smärta, obehag, domningar och balans. Tre mätningar utfördes, före, efter samt åtta veckor efter interventionen. Självrapporterad skattning och fysisk mätning användes. Resultat: Gruppens smärta, obehag och domningar minskade vid samtliga mätningar. För smärta visade mätning efter intervention samt åtta veckor efter signifikans (p=0,027), (p=0,042). Obehag visade signifikans efter interventionen (p=0,018). Domningar visade ingen signifikans. Balans visade signifikans i: Skärpt Romberg, höger, blundande, åtta veckor efter interventionen (p=0,043). Skärpt Romberg, vänster, blundande, efter interventionen (p=0,027), åtta veckor efter interventionen (p=0,028). Stående på ett ben, höger, blundande, efter interventionen (p=0,042), åtta veckor efter interventionen (p=0,027). Inga mätningar visade försämringar. Slutsats: Restultaten visade att behandling med långvårdsdiametri, interferens och balansträning minskade smärta, obehag, domningar och delvis förbättrade balans vid hand-fot syndrom. Dock går det inte att påvisa vilken behandlingskomponent som påverkat mest. Ytterligare studier behövs för att ge resultat större giltighet. / Background: Hand-foot syndrome is a form of perifier sensory neuropathy caused by chemotherapy. The syndrome can cause side effects such as pain, discomfort, numbness, swelling and impaired balance. Evaluated treatment is lacking. Purpose: Examine how twelve week physiotherapy treatment short-wave diathermy, interference and balance training affects side effects of the foot/lower leg caused by chemotherapy in seven patients with hand-foot syndrome. Method: Study group, quasi-experimental outcome study. Seven patients participated. Variables measured were, pain, discomfort, numbness, and balance. Three measurements were carried out, before, after, and eight weeks after the intervention. Self-reported estimates and the physical measurement were used. Results: The group's pain, discomfort and numbness decreased in all measurements. For pain measurement after the intervention and eight weeks after showed significance (p = 0,027),(p = 0,042). Discomfort showed significance after the intervention (p = 0,018). Numbness showed no significance. Balance showed significance in: Sharpened Romberg, left, eyes closed, eight weeks after intervention (p = 0,043). Sharpened Romberg, left, eyes closed, after the intervention (p = 0,027), eight weeks after intervention (p = 0,028). Standing on one leg, the right, eyes closed, after the intervention (p = 0,042), eight weeks after intervention(p = 0,027). No measurements showed deterioration. Conclusion: The results showed that treatment with short-wave diathermy, interference and balance training reduced pain, discomfort, numbness and partial improvements in balance in hand-foot syndrome. However, it is not possible to demonstrate which treatment component that affected the most. Further studies are needed to produce results more valid.