The current study aims to determine physical activity levels among people living with HIV treated with high active antiretroviral therapy in Kigali, Rwanda. A cross-sectional design using quantitative method was used. The participant’s levels of physical activity participation and their association with anthropometric profiles were measured, using a structured selfadministered questionnaire adapted from the Sub-Saharan Africa Activity Questionnaire. Based on a scientific calculation, 407 clients passing through the clinics were included in the study. A convenient sample of people attending the clinics approached to participate voluntarily in the study. The findings of the current study highlighted the lack of motivation, lack of time and fear of worsening the disease amongst the strong barriers to physical activity participation. The current study recommends education about the benefits of physical activity participation and encouragement of patient treated with high active antiretroviral therapy in Rwanda to be emphasized on to improve their lives.

Amplification of the receptor tyrosine kinase ErbB-2 has been linked to the proliferation of breast cancer cells.1,2 Trastuzumab targets the extracellular domain of ErbB-2, leading to growth inhibition of approximately 15% of the breast cancers with genomic amplification of the ERBB2 gene.3 Clinical studies have demonstrated its efficacy in both early4 and metastatic breast cancers. 5,6 However, many tumors with ERBB2 amplification are not responsive to treatment.7 Moreover, the ones that initially respond, eventually progress and acquire drug resistance.8 An in vitro model for this acquired resistance was established by Chan & al.9 The breast cancer cell line, BT474, containing amplified ERBB2, was grown in the presence of trastuzumab for several months until subclones outgrew. Gene expression profiling was performed on these clones to determine differentially expressed genes between the parental and resistant cells. DARPP-32 (Dopamine and cAMP regulated phosphoprotein of 32kDa) was, by far, the most overexpressed transcript. DARPP-32 is coamplified with ERBB2 on the same amplicon of chromosome 17.10 This protein has been mostly described in neurobiology, but DARPP-32 overexpression was recently reported in gastrointestinal, esophageal, prostate and breast cancer.11 Therefore, we suggest that overexpression of DARPP-32 can cause acquired resistance of breast cancer cells to trastuzumab. The in vitro knockout of DARPP-32, using stable shRNA transfection, abolishes the resistance to trastuzumab in the clones, while overexpression of DARPP-32 in the parental cells results in de novo resistance. Overall, our results suggest that DARPP-32 may be a potential therapeutic target in breast cancer patients who develop acquired trastuzumab resistance.

Breast cancer is the most commonly diagnosed cancer in women. Despite recent advances in screening and early detection, breast cancer continues to result in a high incidence of morbidity and mortality. In its late stage the majority of patients exhibit signs of destructive skeletal metastasis. This complication is promoted by the production of growth factors by tumor cells which can induce tumor cell proliferation via their interaction with their respective receptors to initiate the vicious cycle of bone resorption. Inhibition of growth factors signaling through their receptors can therefore serve as a useful therapeutic approach to block bone metastasis. / The biological characteristics of cancer cells along with the targeting properties of immune system offer a novel approach in the treatment of breast cancer. Directed against HER-2/nue oncogene, the recombinant humanized monoclonal antibody, Trastuzumab (Herceptin), has shown significant clinical benefits for the treatment of HER-2 positive metastatic breast cancer. / In the present study, the effects of Herceptin and its molecular mechanism of action in abrogating the development and progression of osteolytic bone metastasis is investigated in an experimental mouse model of skeletal metastasis using human breast cancer cells BT-474 which are known to express high levels of HER-2. Treatment of BT-474 cells with Herceptin caused a dose dependent decrease in cell proliferation. In in vivo studies BT-474 cells were injected by into the left ventricle of female BALB/c nu/nu mice. Intraperitoneal infusion of Herceptin from the day of tumor cell inoculation or at the time of radiologically detectable skeletal metastasis either slowed the development or prevented the progression of skeletal metastasis as compared to control groups of animals receiving non-specific IgG. Bone histological analysis of long bones showed the ability of Herceptin to reduce the ratio of tumor volume to bone volume as well as mitotic index when Herceptin treatment was initiated from the day of tumor cell inoculation. Immunohistochemical analysis of long bones showed a significantly lower level of activated (phosphorylated) MAPK in bones of Herceptin treated animals. These studies demonstrate the ability of Herceptin to inhibit the development and abrogate the progression of skeletal metastasis associated with breast cancer by blocking the HER-2 mediated signaling pathways.

Dissertation (Ph.D.)--University of South Florida, 2008. / Title from PDF of title page. Document formatted into pages; contains 160 pages. Includes vita. Includes bibliographical references.

Thesis (Ph.D. in Nursing) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 190-197). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Resumo: A mucosite é uma das complicações orais mais incidentes relacionadas à quimioterapia, que provoca ulcerações, dor, dificuldade de alimentação e pode levar à interrupção do tratamento antineoplásico. O objetivo deste estudo foi testar o efeito do LED (Ligth Emitting Diode) no tratamento da mucosite induzida por quimioterapia em hamsters. Os animais do grupo experimental (G1) e do grupo controle (G2) receberam injeção de 5-fluoruracila nos dias 0 e 2 do experimento e tiveram as mucosas direita e esquerda arranhadas nos dias 3 e 4. O G1 recebeu tratamento com LED (630 nm, 160 mW, 12 J/cm2) durante 37,5 segundos nos dias 3, 4, 6, 8, 10, 12 e 14. A mucosa jugal foi evertida e fotografada a cada dois dias a partir do dia 4 até o dia 14. As fotografias foram classificadas por meio de uma escala de acordo com o grau de severidade da mucosite (0 a 5). O G2 não recebeu tratamento. O grupo controle negativo (G3) não foi submetido à indução de mucosite. Nos dias 5, 9, 13 e 14, as mucosas de 8 animais (G1 e G2) foram removidas para avaliação histopatológica. A análise estatística demonstrou haver diferenças significantes entre o grupo tratado com LED e o grupo não tratado (p<0,05) quando se comparou a severidade da mucosite, apesar de a avaliação histopatológica ter demonstrado degeneração muscular em aproximadamente 18% da amostra (G1). A aplicação do LED nos parâmetros utilizados neste estudo foi efetiva na redução da severidade da mucosite oral e na cicatrização das lesões, embora não tenha prevenido completamente o surgimento das mesmas. / Abstract: Mucositis is the most common oral complication of cancer chemotherapy that causes pain and impairs patient's ability to eat, swallow and may determine interruption of the treatment. The aim of this study was to evaluate the effect of LED (Ligth Emitting Diode) therapy on chemotherapy-induced mucositis in hamsters. The animals of both experimental (G1) and positive control group (G2) received intraperitoneal injections of 5-fluorouracil on days 0 and 2. All animals had right and left oral mucosa irritated by superficial scratching on days 3 and 4. The G1 received LED irradiation (630 nm, 160 mW, 12 J/cm2) during 37,5 seconds at days 3, 4, 6, 8, 10, 12 and 14. The cheek pouches were everted and photographed from day 4 until 14 at 2-day intervals. Photographs were randomly scored according to the severity of induced mucositis (0 to 5). The G2 received no treatment. The negative control group (G3) received no mucositis induction. The cheek pouches of 8 animals (G1 and G2) were dissected for histopathological examination on days 5, 9, 13 and 15. The statistical analysis showed significant differences between treated and non-treated groups (p<0,05), although histopathological findings have demonstrated muscular degeneration in 18% of the sample (G1), approximately. These results pointed out that LED therapy protocol established for this study was effective to reduce the severity of oral mucositis and accelerated the healing process, although it has not completely prevented the appearance of oral lesions. / Orientador: Fabio Cesar Braga de Abreu e Lima / Coorientador: Carlos Alberto de Souza Costa / Banca: Elisa Maria Aparecida Giro / Banca: Rosane de Fátima Zanirato Lizarelli / Mestre

Made available in DSpace on 2016-12-23T13:53:40Z (GMT). No. of bitstreams: 1 Marcio Paiva Barcellos.pdf: 785021 bytes, checksum: 7244ddbb83147994e7b408bc5e47e680 (MD5) Previous issue date: 2013-07-19 / American cutaneous leishmaniasis (ACL) is a widespread disease in several countries. As recommended by the Brazilian Ministry for Health, a treatment of animals is contraindicated. The aim of this study was to test the use of furazolidone (FZ) to treat lesions in dogs suffering from ACL. The study was conducted with nine dogs with lesions and the presence of ACL as confirmed by ELISA and PCR for biopsy and culture for Leishmania (V.) braziliensis. The drug was administered orally in a concentration of 20 mg / kg every twelve hours for seven days, in three steps with an interval of 10 days, accompanied by laboratory monitoring of hematological and biochemical patterns. A regression of the lesion was observed in seven animals. FZ has proven an effective drug in the remission of lesions in dogs with ACL injury / A leishmaniose tegumentar americana (LTA) é uma doença difundida em diversos países e os derivados antimoniais pentavalentes são as drogas de escolha no tratamento desta enfermidade para humanos, porém como recomendado pelo Ministério da Saúde, é contra indicado para o tratamento em animais, justificando a busca de novas terapias para o tratamento da LTA em caninos. O objetivo deste trabalho foi testar o uso da furazolidona (FZ) no tratamento de lesões cutâneas em cães portadores de LTA. O estudo foi feito em nove cães com lesões da doença confirmados por técnicas de ELISA, biópsia para PCR e cultura para Leishmania (V.) braziliensis. O medicamento foi administrado via oral na dosagem de 20 mg/Kg a cada doze horas durante sete dias, em três etapas com intervalo de 10 dias, foram realizados exames laboratoriais para monitoramento dos padrões hematológicos e bioquímicos. A regressão da lesão foi observada em 77,77% dos animais, o que demonstrou o efeito terapêutico da droga no tratamento clínico das lesões dos cães com LTA

BACKGROUND: Despite the high number of methamphetamine users in the Czech Republic, the treatment is still only abstinent. Pharmacotherapy in terms of substitution treatment is not yet in place. No study has yet been conducted to examine the views of workers working with methamphetamine users on the possibility of introducing substitution treatment for methamphetamine dependence in the Czech Republic. OBJECTIVE: The aim of the practical part was to map the opinions of outpatient staff on the possibility of introducing substitution treatment for methamphetamine dependence. The monitored area included the evaluation of the success of the treatment of methamphetamine dependence in outpatient settings, disparity in working with users by substance use, percentage of methamphetamine users in the facilities, the suitability of drug addiction to methamphetamine for clients of outpatient facilities and position of substitution treatment for methamphetamine, according to respondents. METHOD: The sample was elected on the basis of deliberate targeted selection through the institutions. Data capture was performed using a semi-structured interview method, which was recorded using audio recording and then transcribed. The data capture method was used to analyze the data. FILES: The research team consisted of...

INTRODUCTION. The greater predisposition to chronic diseases and consequent use of various medications in the elderly increases the chances of the use of potential inappropriate drug therapy (PIDT). The damaging effects of PIDT boosted professionals to develop methods to identify patterns of prescription PIDT in different countries and practice scenarios. PURPOSE Assess FPII the light of the scientific literature. METHODOLOGY. The study was structured in three stages. The first corresponded to a systematic review to identify what are the assessment tools used by the world FPII and investigate what are the terms used to refer to FPII. The second stage corresponded to a systematic review aimed to assess the methodological rigor of studies evaluating FPII. The third step corresponds to a meta-analysis that evaluated the association FPII with risk factors, age, sex and polypharmacy. RESULTS. The instrument most commonly used in the literature is the one proposed by Beers. Found more than 50 terms to refer to PIDT. Of the studies reviewed, none fulfilled all items proposed by the Strengthening the Reporting of Observational Studies in Epidemiology. Only polypharmacy had a positive association with the use of FPII. CONCLUSION. These findings should guide future research in this area, offering a more complete approach on aspects related to the use of medications for this specific population. / INTRODUÇÃO. A maior predisposição a doenças crônicas e consequente uso de vários medicamentos nos idosos, aumenta a chances do uso de farmacoterapia potencialmente inapropriada ao idoso (FPII). Os efeitos prejudiciais da FPII impulsionaram profissionais a desenvolverem métodos para identificar padrões de prescrição de FPII em diferentes países e cenários de prática. OBJETIVO. Avaliar a FPII à luz da literatura científica. METODOLOGIA. O estudo foi estruturado em três etapas. A primeira correspondeu a uma revisão sistemática a fim de identificar quais são os instrumentos de avaliação de FPII utilizados pelo mundo, bem como investigar quais são os termos utilizados para se referir a FPII. A segunda etapa correspondeu a uma revisão sistemática que objetivou avaliar o rigor metodológico dos estudos que avaliam FPII. A terceira etapa correspondeu a uma metanálise que avaliou a heterogeneidade de estudos que avaliam a associação de FPII com os fatores de risco; idade, sexo e polifarmácia. RESULTADOS. O instrumento mais utilizado pela literatura é o proposto por Beers. Foram encontrados mais de 50 termos para se referir a FPII. Dos estudos analisados, nenhum cumpriu todos os itens propostos pela Strengthening the Reporting of Observational Studies in Epidemiology. Apenas a polifarmácia teve associação positiva com o uso de FPII. CONCLUSÃO. Estes resultados devem orientar futuras pesquisas nesta área, oferecendo uma abordagem mais completa sobre os aspectos relacionados com o uso de medicamentos por esta população específica.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / To evaluate the impact of a drug therapy follow up program in a group of elderly patients with Diabetes Mellitus assisted in the Farmácia Popular of Aracaju-SE. Methodology: A longitudinal, prospective and intervention study was carried out from February to November 2009, in the Farmácia Popular of Brazil, in the city of Aracaju - SE. A sample of convenience and not probabilistic of elderly between 60 and 75 years, of both genders, was obtained. It was scheduled monthly visits during a period of 10 months. The nine steps of good practice of Pharmaceutical Care (PC) were followed in this study. Throughout the visits were obtained sociodemographic, clinical and drug therapy profiles (glycated hemoglobin - HbA1c, capillary glucose, blood pressure - BP, body mass index - BMI, and waist circumference). Assessment of Quality of Life was made by a generic tool called Medical Outcomes Studies 36 - item Short Form - SF-36 ®. In total, 50 patients were invited to participate in the PC program, in which 34 of them completed the study (dropout rate = 32%). The mean age of the elderly was 65.94 ± 4.73 years, and 18 (52.94%) were female. Regarding marital status, there was a predominance of married patients (73.52%, n = 25) and 50% (n = 17) of them had basic educational level. In this study, the mean number of medications by elderly was 6.23 (± 2.20) and 28 patients (82.35%) used five or more medications, featuring the use of polypharmacy. A total of 117 Drug Therapy Problems (DTP) were identified, with a mean of 3.44 (+1.94) DTP per patient. The highest incidence of DTP was categorized as effectiveness (29.06%), followed by DTP compliance (25.64%). During follow-up, 101 were solved DTP (86.32%). There were significant differences in measures of HbA1c, capillary glucose, BP (systolic and diastolic) and waist circumference before and after PC interventions (p <0.05). It was also found significant differences between baseline and final evaluation in the domains of quality of life assessed, such as physical functioning, role physical, bodily pain, general health, vitality and mental health. The educational PC interventions were factors that contribute to the awareness of elderly on the Diabetes reducing and preventing DTP and its complications. Thus, co-responsibility and active participation of the elderly may have improved the use of drug therapy and its clinical and humanistic outcomes. / Avaliar o impacto de um programa de acompanhamento farmacoterapêutico em um grupo de idosos com Diabetes Melito assistidos na Farmácia Popular de Aracaju-SE. Metodologia: foi realizado um estudo longitudinal, prospectivo e com intervenção no período de fevereiro a novembro de 2009, na Farmácia Popular do Brasil, no município de Aracaju SE. Foi obtida uma amostra por conveniência e não probabilística com faixa etária entre 60 e 75 anos, de ambos os gêneros. Foram agendadas consultas mensais, durante o período de dez meses e as nove etapas de boa prática da AtenFar foram seguidas. Ao longo dos atendimentos foram obtidos dados sócio-demográficos, farmacoterapêuticos e clínicos (Hemoglobina Glicosilada HbA1c, Glicemia Capilar, Pressão Arterial PA, Índice de Massa Corporal IMC, e Circunferência da Cintura). A avaliação da Qualidade de Vida foi realizada por um instrumento genérico denominado Medical Outcomes Studies 36 - item Short Form - SF36®. No total, 50 pacientes foram convidados a participar do programa de Atenfar, destes 34 completaram o estudo (taxa de abandono = 32%). A média de idade dos idosos foi 65.94 ± 4,73 anos, sendo 18 (52,94%) participantes do gênero feminino. Quanto ao estado civil, houve predominância de pacientes casados (73,52%, n = 25) e 50% (n = 17) dos idosos apresentaram nível fundamental de escolaridade. Neste estudo, a média de medicamentos por idoso foi de 6,23 (± 2,20) e 28 pacientes (82,35%) usavam cinco ou mais medicamentos, caracterizando a utilização de polifarmácia. No total, 117 PRM foram identificados, com uma média de 3,44 (+1,94) PRM por paciente. A maior incidência de PRM categorizado foi de Efetividade (29,06%), seguido por PRM de Cumprimento (25,64%). Durante o acompanhamento aos pacientes, 101 PRM foram resolvidos (86,32%). Os pacientes obtiveram diferença significativa das medidas de HbA1c, Glicemia Capilar, PA (sistólica e diastólica) e Circunferência da Cintura, antes depois das intervenções farmacêuticas (p < 0,05). Os domínios da Qualidade de Vida avaliados pelo SF36®: capacidade funcional, aspectos físicos, dor, estado geral de saúde, vitalidade e saúde mental tiveram diferença significativa entre a linha de base e avaliação final. As intervenções farmacêuticas destinadas a resolver e prevenir PRM, associadas às intervenções educativas, são fatores que contribuem para a conscientização dos idosos sobre o DM e suas complicações. Assim, a coresponsabilização e a participação ativa dos idosos podem ter melhorado o uso da farmacoterapia e os seus resultados clínicos e humanísticos.