Este estudo descreveu a utilização do cateter venoso central totalmente implantável (CVC-TI) e o comparou ao cateter venoso periférico (CVP) para sessões de quimioterapia em cães. Foram utilizados onze cães com diagnóstico de linfoma e que necessitavam do tratamento quimioterápico. Seis cães tiveram implantado na veia jugular externa direita um CVC-TI através da técnica de “Seldinger”, pelo qual receberam a medicação durante as sessões de quimioterapia. Outros cinco cães utilizaram o CVP convencional para o tratamento. Foram comparados a variação da pressão arterial sistólica, o tempo de manipulação do animal e o número de punções necessárias nas sessões de quimioterapia de ambos os grupos. O grupo CVC-TI apresentou redução da pressão arterial sistólica e menor tempo de manipulação do animal durante as sessões. Não houve diferença quanto ao número de punções entre os grupos. Amostras sanguíneas coletadas através do dispositivo foram fidedignas às convencionais. O CVC-TI, quando comparado ao CVP, se mostrou útil para reduzir o desconforto da manipulação dos cães em tratamento quimioterápico. / This study described the use of totally implantable vascular access port (TI-VAC), compared to peripheral venous catheter (PVC) for chemotherapy sessions in dogs. Eleven dogs diagnosed with lymphoma and requiring chemotherapeutic treatment were included in the study. Six dogs had a TI-VAC implanted in the right external jugular vein through the "Seldinger” technique, for which they received the medication during the chemotherapy sessions. Five other dogs used conventional PVC for treatment. The systolic blood pressure variation, the time of animal’s manipulation and the number of punctures needed in the chemotherapy sessions of both groups were compared. The TI-VAC group presented systolic blood pressure reduction and shorter time of animal’s manipulation during the sessions. There was no difference in the number of punctures between groups. Blood samples collected through the device were reliable to conventional ones. The TI-VAC, when compared to PVC, was shown to be useful for reducing discomfort of dogs undergoing chemotherapy.

O Melanoma é um tipo de neoplasia que se origina de melanócitos normalmente presentes na epiderme. Uma das características do melanoma é a capacidade de adquirir resistência a terapias. As células de melanoma podem aumentar a liberação de vesículas extracelulares (VEs) em resposta ao tratamento com quimioterápicos. A cisplatina (CDDP) e a temozolomida (TMZ) são drogas utilizadas para o tratamento de tumores. Ambas as drogas formam adutos no DNA, mas as vias de sinalização que deflagram a morte celular são distintas. O objetivo desse estudo é investigar a morte celular da linhagem B16-F10 na presença de VEs oriundas de células B16-F10 tratadas com cisplatina CDDP ou TMZ. Inicialmente as VEs oriundas de células de melanoma murino, B16-F10, tratadas com CDDP ou TMZ e seus controles, foram isoladas por ultracentrifugações sucessivas. Para os experimentos in vitro, as células foram tratadas com as drogas em combinação com as respectivas VEs. As amostras foram realizados avaliações de ciclo celular e de morte e ensaio clonogênico. Para os experimentos in vivo, as células B16-F10 foram pré-tratadas com VEs, e posteriormente, as células foram inoculadas via subcutânea em camundongos C57BL/6 e os tumores foram mensurados diariamente. Em nosso estudo concluimos que a metodologia do isolamento de VEs é eficiente. Além disso, observamos que o tratamento com CDDP ou TMZ aumenta a liberação de VEs por células tumorais. Apesar do resultado contraditorio, as VEs liberadas por células tumorais tratadas com quimioterápicos aumentam a capacidade de sobrevivência das células de melanoma in vitro. VEs oriundas de células de melanoma não participam inicialmente da sensibilização à morte de células tumorais causada pelas mesmas drogas, mas a longo prazo, as VEs oriundas de células tratadas com a TMZ podem conferir uma resposta celular de sobrevivência às células tumorais in vitro. In vivo, o resultado é inconclusivo, uma vez que para confirmar se as VEs fazem parte da adaptação tumoral conferindo fenômenos de sobrevivência celular in vivo, é necessário avaliar em outros modelos celulares e animais / Melanoma is a neoplasm derived from melanocytes normally present in the skin specifically in the epidermis. One of the malignancies of melanoma is the ability to acquire chemoresistance. Cisplatin (CDDP) and temozolomide (TMZ) are drugs used for the treatment of tumors. Both drugs can form alkylating adducts in DNA, however, the pathways that trigger cell death are distinct. Tumor cells, including melanoma, may increase the release of extracellular vesicles (EVs) in response to chemotherapeutic treatment. The aim of this study is to investigate the cell death phenomenon in B16-F10 cell line in presence of EVs derived from chemotherapeutic-treated B16-F10 cells. For in vitro experiments, the cells were treated with CDDP or TMZ in combination with EVs from chemotherapictreated samples. For in vivo experiments, B16-F10 cells were exposed to EVs and inoculated subcutaneously in C57BL/6 mice. The growth was measured daily. In this work, we established and characterized VEs released by melanoma cells treated with chemotherapics and we established chemotherapics treatments to isolate EVs for next EVs isolation. Our results showed that CDDP or TMZ treatment increase the release of EVs by tumor cells. The EVs released by melanoma cells after CDDP or TMZ treatment seem to increase the survival capacity of melanoma cells. Thus, we concluded that EVs derived from melanoma cells do not participate in the cell death sensitization induced by CDDP or TMZ. However, EVs derived from TMZ treated cells may offer a survival effect to tumor cells in vitro a long term. In vivo, The result is inconclusive since to confirm how VEs are part of the tumor adaptation conferring cellular survival phenomena in vivo, it is necessary to evaluate in other cellular and animal models

Aim: To determine and compare the prevalence of CCR5-Δ32 and CCRV64I genes in HIV positive and HIV negative population of pregnant women from Harare, in Zimbabwe.Results: The proportion of pregnant women with the homozygous CCR2V64I gene was 24.38% and this gene was two times more associated with HIV infection than in those without it ( RR= 2.32, 95% CI-1.38-3.92). No CCR5-Δ32 deletion was detected in the studied population. Conclusion: The homozygous CCR2V64I gene and STIs were more prevalent in HIV infected pregnant women than in uninfected pregnant women and no homozygous CCR5-Δ32 gene was detected in this study.

Aim: To determine and compare the prevalence of CCR5-Δ32 and CCRV64I genes in HIV positive and HIV negative population of pregnant women from Harare, in Zimbabwe.Results: The proportion of pregnant women with the homozygous CCR2V64I gene was 24.38% and this gene was two times more associated with HIV infection than in those without it ( RR= 2.32, 95% CI-1.38-3.92). No CCR5-Δ32 deletion was detected in the studied population. Conclusion: The homozygous CCR2V64I gene and STIs were more prevalent in HIV infected pregnant women than in uninfected pregnant women and no homozygous CCR5-Δ32 gene was detected in this study.

OBJECTIVE: Low level light therapy (LLLT) is being widely used in wound healing and pain relief, and its use is expected to be expanded rapidly to treatment of other disorders as well in a foreseeable future. However, before its expansion, the fear that LLLT could initiate or promote metastasis must be addressed thoroughly. As an initial effort towards this end, the current study evaluates the safety of LLLT in vitro using two different human cancer cell lines (Michigan Cancer Foundation-7 (MCF-7) and Jurkat E6-1) by determining the viability of cells after low level light (LLL) application while treatment under anti-cancer chemotherapeutic drugs (5-fluorouracil (5-FU) and cisplatin) separately on each cell line. METHODS: Two human cancer cell lines (MCF-7 and Jurkat E6-1) were cultured throughout the experiments. Two different anti-cancer chemotherapeutic drugs (5-FU and cisplatin) were used to treat both cell lines. The half maximal inhibitory concentration (IC50) of each drug on each cell line was determined by treating each cell line with varying concentrations of each drug. A total of 3 or 4 trials were done for each cell line with each drug, and the range of concentration was narrowed closer to the IC50 value at each successive trial. Once the IC50 concentrations were determined, each cell line was treated with 808 nm LLL at varying energy densities in a single dose using a light emitting diode (LED) source both in the absence and the presence of each drug at one IC50. A total of 3 or 5 trials were done for each cell line with each drug, and for each trial, six different energy densities ranging from 0 J/cm2 (control) to 10 J/cm2 were applied. The energy densities were varied for each trial with control always being used. After application of LLL, the viability of cells was determined, and three different 1-way ANOVA (Analysis of Variance) analyses were done to compare the viability of cells at each energy density to that of control. RESULTS: The IC50 of 5-FU in MCF-7 and Jurkat E6-1 cells was determined as 70 µM and 20 µM respectively. The IC50 of cisplatin in MCF-7 and Jurkat E6-1 cells was determined as 17 µM and 7 µM respectively. No significant difference (P > 0.05) in the viability of MCF-7 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of 5-FU at IC50 (70 µM). No significant difference (P > 0.05) in the viability of MCF-7 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of cisplatin at IC50 (17 µM). No significant difference (P > 0.05) in the viability of Jurkat E6-1 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of 5-FU at IC50 (20 µM). However, a significant increase (0.01 < P < 0.05) in the viability of cells was observed when treating Jurkat E6-1 cells with 10 J/cm2 of LLL in the presence of cisplatin at IC50 (7 µM) compared to control group (0 J/cm2). Except for the comparison mentioned previously, no significant difference in the viability of Jurkat E6-1 cells was observed between each group treated with different energy density of LLL and control group (0 J/cm2) both in the absence and the presence of cisplatin at IC50 (7 µM). No definite trend in the viability of cells was observed with increasing energy density of LLL for each cell line either in the absence of the presence of each drug at IC50. CONCLUSIONS: The application of LLL at 808 nm with energy densities ranging from 0.1 J/cm2 to 10 J/cm2 under an LED source did not induce cell proliferation or death compared to control (0 J/cm2) for each cell line in the absence or the presence of each drug, and no definite trend was observed with increasing energy density. The study suggests that LLLT at these parameters may be safe to use on cancer patients, but further studies on different cancer cell lines and animal models with different parameters (wavelength, energy density, dosage) of LLL are warranted.

Este estudo descreveu a utilização do cateter venoso central totalmente implantável (CVC-TI) e o comparou ao cateter venoso periférico (CVP) para sessões de quimioterapia em cães. Foram utilizados onze cães com diagnóstico de linfoma e que necessitavam do tratamento quimioterápico. Seis cães tiveram implantado na veia jugular externa direita um CVC-TI através da técnica de “Seldinger”, pelo qual receberam a medicação durante as sessões de quimioterapia. Outros cinco cães utilizaram o CVP convencional para o tratamento. Foram comparados a variação da pressão arterial sistólica, o tempo de manipulação do animal e o número de punções necessárias nas sessões de quimioterapia de ambos os grupos. O grupo CVC-TI apresentou redução da pressão arterial sistólica e menor tempo de manipulação do animal durante as sessões. Não houve diferença quanto ao número de punções entre os grupos. Amostras sanguíneas coletadas através do dispositivo foram fidedignas às convencionais. O CVC-TI, quando comparado ao CVP, se mostrou útil para reduzir o desconforto da manipulação dos cães em tratamento quimioterápico. / This study described the use of totally implantable vascular access port (TI-VAC), compared to peripheral venous catheter (PVC) for chemotherapy sessions in dogs. Eleven dogs diagnosed with lymphoma and requiring chemotherapeutic treatment were included in the study. Six dogs had a TI-VAC implanted in the right external jugular vein through the "Seldinger” technique, for which they received the medication during the chemotherapy sessions. Five other dogs used conventional PVC for treatment. The systolic blood pressure variation, the time of animal’s manipulation and the number of punctures needed in the chemotherapy sessions of both groups were compared. The TI-VAC group presented systolic blood pressure reduction and shorter time of animal’s manipulation during the sessions. There was no difference in the number of punctures between groups. Blood samples collected through the device were reliable to conventional ones. The TI-VAC, when compared to PVC, was shown to be useful for reducing discomfort of dogs undergoing chemotherapy.

Made available in DSpace on 2016-06-02T19:19:55Z (GMT). No. of bitstreams: 1 MARTINS_Kelly_2013.pdf: 1489805 bytes, checksum: 32aed5a1b752893511324c4670fcbcd5 (MD5) Previous issue date: 2013-02-05 / Financiadora de Estudos e Projetos / In order to minimize the side effects of chemotherapy concurrently with the enhancement of its therapeutic action is to use it on devices that enable a controlled drug release, by vectors, such as polymeric microspheres, which act as a drug carrier, modifying its distribution pattern in the organism. Paclitaxel ((Taxol®) is a drug used primarily in the treatment of ovarian, breast, lung and bladder cancer. Due to its antimitotic and antiproliferative action, there is a potential interest in cancer therapy. However, the success of this clinical application is limited to low solubility in water and toxic action. The objective of this study was to obtain and characterize physic-chemically the bioresorbable and biocompatible copolymer poly (L-co-D, L lactic acid) (PLDLA) microspheres encapsulating the paclitaxel chemotherapy. The simple emulsion technique allowed to obtain spherical microspheres, verified by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The average size of the microspheres PLDA pure and containing paclitaxel were, respectively, 10.3 &#956;m ± 1.7 and 12.7 &#956;m ± 1.3, obtained by the technique of laser light scattering (LLS). Moreover the essay of differential scanning calorimetry (DSC) suggests that the drug paclitaxel is homogeneously dispersed in the microspheres PLDLA. The encapsulation efficiency of the microspheres PLDLA paclitaxel was 98.0% ± 0.3, obtained by high performance liquid chromatography (HPLC). The in vitro release study performed on HPLC showed initial burst release followed by a slower release, which characterizes large diameter distribution systems. PLDLA microspheres released 90% ± 4.0 of the drug paclitaxel up to 30th day of study while the degradation process occurred. Thus, the microspheres obtained PLDLA devices are promising as carriers of paclitaxel, with potential for future applications in drug delivery systems. / Uma forma de minimizar os efeitos colaterais de quimioterápicos concomitantemente ao processo de potencialização de sua ação teraupêutica é empregá-los em dispositivos de liberação controlada de drogas, por meio de veículos, como microesferas poliméricas, que agem como carreadores de fármacos, modificando seu perfil de distribuição no organismo. O paclitaxel (Taxol®) é um quimioterápico utilizado principalmente no tratamento do câncer de ovário, mama, pulmão e bexiga. Devido à sua relevante ação antimitótica e antiproliferativa, existe potencial interesse de seu uso na terapia do câncer, porém o sucesso de sua aplicação clínica é limitado devido sua baixa solubilidade em água e sua ação tóxica. O objetivo desse estudo foi o de obter e caracterizar, físico-quimicamente, microesferas do copolímero biorreabsorvível e biocompatível poli(L-co-D,L ácido láctico) (PLDLA) encapsulando o quimioterápico paclitaxel. A técnica de simples emulsão permitiu a obtenção de microesferas na forma esférica, verificado por microscopia eletrônica de varredura (MEV) e microscopia de força atômica (AFM). O tamanho médio das microesferas de PLDLA puro e contendo paclitaxel, foi, respectivamente, de 10,3&#956;m±1,7 e 12,7&#956;m±1,3, obtidos pela técnica de espalhamento de luz laser (LLS). Já o ensaio de calorimetria diferencial exploratória (DSC), sugere que o fármaco paclitaxel está disperso de forma homogênea nas microesferas de PLDLA. A eficiência de encapsulação do paclitaxel nas microesferas de PLDLA foi de 98,0%±0,3, obtidos pela cromatografia líquida de alta eficiência (HPLC). O estudo de liberação do fármaco in vitro realizado no HPLC apresentou liberação inicial em explosão, seguida de uma liberação mais lenta, características de microesferas que apresentam diâmetros variados. As microesferas de PLDLA liberaram 90%±4,0 do fármaco paclitaxel até o 30° dia de estudo enquanto se degradavam. Assim, as microesferas de PLDLA obtidas são dispositivos promissores como carreadores do paclitaxel, com potencial para futura aplicação em sistemas de liberação de fármacos.

Este estudo descreveu a utilização do cateter venoso central totalmente implantável (CVC-TI) e o comparou ao cateter venoso periférico (CVP) para sessões de quimioterapia em cães. Foram utilizados onze cães com diagnóstico de linfoma e que necessitavam do tratamento quimioterápico. Seis cães tiveram implantado na veia jugular externa direita um CVC-TI através da técnica de “Seldinger”, pelo qual receberam a medicação durante as sessões de quimioterapia. Outros cinco cães utilizaram o CVP convencional para o tratamento. Foram comparados a variação da pressão arterial sistólica, o tempo de manipulação do animal e o número de punções necessárias nas sessões de quimioterapia de ambos os grupos. O grupo CVC-TI apresentou redução da pressão arterial sistólica e menor tempo de manipulação do animal durante as sessões. Não houve diferença quanto ao número de punções entre os grupos. Amostras sanguíneas coletadas através do dispositivo foram fidedignas às convencionais. O CVC-TI, quando comparado ao CVP, se mostrou útil para reduzir o desconforto da manipulação dos cães em tratamento quimioterápico. / This study described the use of totally implantable vascular access port (TI-VAC), compared to peripheral venous catheter (PVC) for chemotherapy sessions in dogs. Eleven dogs diagnosed with lymphoma and requiring chemotherapeutic treatment were included in the study. Six dogs had a TI-VAC implanted in the right external jugular vein through the "Seldinger” technique, for which they received the medication during the chemotherapy sessions. Five other dogs used conventional PVC for treatment. The systolic blood pressure variation, the time of animal’s manipulation and the number of punctures needed in the chemotherapy sessions of both groups were compared. The TI-VAC group presented systolic blood pressure reduction and shorter time of animal’s manipulation during the sessions. There was no difference in the number of punctures between groups. Blood samples collected through the device were reliable to conventional ones. The TI-VAC, when compared to PVC, was shown to be useful for reducing discomfort of dogs undergoing chemotherapy.

Magister Public Health - MPH / Aim: To determine and compare the prevalence of CCR5-Δ32 and CCRV64I genes in HIV positive and HIV negative population of pregnant women from Harare, in Zimbabwe. Results: The proportion of pregnant women with the homozygous CCR2V64I gene was 24.38% and this gene was two times more associated with HIV infection than in those without it ( RR= 2.32, 95% CI-1.38-3.92). No CCR5-Δ32 deletion was detected in the studied population. Conclusion: The homozygous CCR2V64I gene and STIs were more prevalent in HIV infected pregnant women than in uninfected pregnant women and no homozygousCCR5-Δ32 gene was detected in this study. / South Africa

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