Evaluation of nuclear NF-κB, transglutaminase2, and ERCC1 as predictors of platinum resistance in testicular tumors

ABSTRACT Purpose: Testicular germ cells tumor (TGCT) are associated with a high cure rate and are treated with platinum-based chemotherapy. However, a group of testicular cancer patients may have a very unfavorable evolution and insensitivity to the main therapeutic agent chemotherapy (CT) cisplatin. The aim of this study was to evaluate the risk of recurrence and overall survival related to the expression of nuclear factor kappa-B (NF-κB), transglutaminase 2 (TG2) and excision repair cross-complementation group 1 (ERCC1) in patients with TGCT treated with platinum combinations. Patients and Methods: A retrospective study was performed with TGCT patients treated with platinum-based chemotherapy. Immunohistochemical analysis was performed and the expression was correlated with clinical and laboratory data. Results: Fifty patients were included, the mean age was 28.4 years (18 to 45), and 76% were non-seminoma. All patients were treated with standard cisplatin, etoposide and bleomycin or cisplatin, and etoposide. Patient's analyzed immunodetection for NF-κB, TG2, and ERCC1 were positive in 76%, 54% and 42%, respectively. Multivariate analysis identified that positive expressions to ERCC1 and NF-κB are independent risk factors for higher recurrence TGCT after chemotherapy (RR 2.96 and 3.16, respectively). Patients with positive expression of ERCC1 presented a poor overall survival rate for 10-year follow (p=0.001). Conclusions: The expression of ERCC1 and NF-κB give a worse prognosis for relapse, and only ERCC1 had an influence on the overall survival of TGCT patients treated with platinum-based chemotherapy. These may represent markers that predict poor clinical outcome and response to cisplatin.

Citotoxic activity evaluation of essential oils and nanoemulsions of Drimys angustifolia and D. brasiliensis on human glioblastoma (U-138 MG) and human bladder carcinoma (T24) cell lines in vitro

The species Drimys angustifolia Miers and D. brasiliensis Miers, commonly known as "casca-de-anta", have in their leaves essential oils that can confer cytotoxic effects. In this study, we evaluated the citotoxic effects of the volatile oils from these two species. We also proposed a nanoemulsion formulation for each of the species and assessed the in vitro cytotoxicity on U-138 MG (human glioblastoma) and T24 (human bladder carcinoma) cell lines. The plant chemical composition was evaluated by gas chromatography coupled to mass spectrometer. Furthermore, the nanoemulsions were prepared and characterized. Our results showed that; bicyclogermacrene (19.6%) and cyclocolorenone (18.2%) were the most abundant for the D angustifolia oil and D brasiliensis oil, respectively. Both nanoemulsions, D angustifolia and D brasiliensis appeared macroscopically homogeneous and opalescent bluish liquids, with nanometric mean diameters of 168 nm for D brasiliensis and 181 nm for D angustifolia. The polydispersity indices were below 0.10, with an acid pH of 4.7-6.3, and negative zeta potentials about -34 mV. The results of transmission electron microscopy showed that droplets are present in the nanometer range. Only the D brasiliensis oil was efficient in reducing the cell viability of both U-138 MG (42.5%±7.0 and 67.8%±7.8) and T24 (33.2%±2.8, 60.3%±1.6 and 80.5%±8.8) cell lines, as assessed by MTT assay. Noteworthy, similar results were obtained with cell counting. Finally, D brasiliensis oil incubation caused an increase of annexin-V and propidium iodite population, according to evaluation by cytometry analysis, what is characteristic of late apoptosis. The results presented herein lead us to consider the potential therapeutic effects of the essential oils and nanoformulations as novel strategies to inhibit tumor growth.

Toxicity of capecitabine compared with 5-fluorouracil in elderly patients with breast or gastrointestinal tract cancer

OBJECTIVES: The aim of this study was to evaluate the toxicity of capecitabine compared with 5-fluorouracil in elderly patients with breast or gastrointestinal tract cancer. MATERIAL AND METHODS: A cohort study was used to evaluate toxicity parameters in elderly patients undergoing chemotherapy treatment. This study was conducted between 2006 and 2008 and was composed of 76 patients from the Oncology Ambulatory of Hospital São Lucas, PUCRS. Eligible patients included elderly individuals (aged 60 years or above) of both sexes who suffered from breast or gastrointestinal tract cancer and who used daily oral capecitabine or intravenous 5-fluorouracil. General side effects were evaluated and graded on a four-point scale. The study also analyzed the values of blood markers such as alanine aminotransferase and aspartate aminotransferase for hepatic toxicity, and troponine I and electrocardiogram for cardiotoxicity. RESULTS: The data showed a higher frequency of general adverse effects in the patients who used 5-fluorouracil in relation of capecitabine. However, only the patients that used capecitabine suffered from hand-and-foot syndrome. Conversely, the levels of ALT in the elderly men who used capecitabine were significantly higher (p = 0.027) than those who used 5-fluorouracil. With regard to cardiac function, a significant difference (p = 0.023) in the median QT interval between the groups was found, while all the other exams presented normal results. CONCLUSION: The use of capecitabine should be frequently monitored in order to minimize or avoid the toxic effects of the chemotherapy in elderly patients. Other parameters should be subsequently analyzed to confirm this conclusion.

Prevalência de diabete mellitus e correlação entre testes de glicemia em pacientes idosos atendidos no ambulatório do Instituto de Geriatria e Gerontologia, PUCRS / Prevalence of diabetes mellitus and correlation between tests of glucose in elderly patients

Este artigo visa correlacionar os diferentes testes de glicemia em pacientes idosos atendidos no Ambulatório do IGG, PUCRS, bern como demonstrar a prevalência de Diabete Mellitus nesta população. Entre 355 idosos avaliados no estudo, 66 (18,59 %) foram diagnosticados diabéticos. Foram avaliadas a glicemia de jejum, a glicemia média estimada (GME) e o hemoglicoteste (HGT) de 33 pacientes sendo 28 mulheres e 5 homens, com uma idade media de 74 anos. Os resultados da GME, HGT e glicemia, apresentaram valores acima das metas em 16 (48,0 %), 9 (27,0 %) e 7 (21,0 %) pacientes, respectivamente. A análise estatfstica demonstra uma diferença significativa nos resultados apresentados por homens e mulheres, estando as mulheres em uma situação considerada adequada em relação aos níveis glicêmicos e os homens apresentando valores muito acima das metas. 0 estudo estatístico demonstrou existir uma correlação muito significativa (p < 0,0001) entre os valores da glicemia de jejum e da hemoglobina glicada (A1c) das mulheres, embora a correlação entre aA1ce o HGT não seja significativa (p <0,59). A correlação entre os valores da glicemia de jejum e da A1c demonstrou não ser significativa (p< 0,75). Entretanto a A1c e o HGT demonstraram-se fortemente correlacionados (p < 0,01).

This paper aims to correlate the different tests of blood glucose in elderly patients treated at the IGG, PUCRS, as well as to demonstrate the prevalence of DM in this population. Among 355 individuals evaluated in the study, 66 (18.59%) were diagnosed with diabetes. We have measured the fasting blood glucose, the estimated average glucose and hemoglucotest of 33 patients with 28 women and 5 men, with a mean age of 74 years. The results of eAG, HGT, showed values above the targets in 16 (48.0 %), 9 (27.0 %) and 7 (21.0 %) patients, respectively. The statistical analysis showed a significant difference in the results presented by men and women, with women in a situation deemed appropriate in regard to the blood glucose levels and men with values well above the targets. Statistical analysis demonstrated that there was a vety significant correlation (p <0.0001) between the values of fasting blood glucose and A1c women, although the correlation between A1c and HGT is not significant (p <0.59). The correlation between the values of fasting plasma glucose and A1c showed not significant (p <0.75). However, theA1c and HGT showed to be strongly correlated (p <0.01).

Effect of temozolomide treatment on the adenine nucleotide hydrolysis in blood serum of rats with implanted gliomas

Objective: Adenine nucleotides and adenosine have many important functions in the physiological and pathological conditions. The measurement of these nucleotides in serum may be an auxiliary tool in the identification of cellular damage in many pathological conditions. The aim of this study is to examine the effect of chemotherapy treatment on nucleotide hydrolysis in the serum of rats following glioma implantation. Methods: C6 glioma cells were injected in the right striatum of 60 day-old Wistar rats, and 20 days after the induction of gliomas, blood serum samples were prepared for measurement of ATP and AMP hydrolysis. Results: The pathological analysis showed that the malignant gliomas induced by C6 injection and treated with temozolomide exhibited a reduction in malignant characteristics. The results demonstrated that the rats that underwent temozolomide treatment had a significant decrease (p<0.05) in blood serum hydrolysis of ATP and AMP when compared with the glioma group. None of the animals included in this study presented significant alterations in the activities of the serum enzymes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Conclusion: The decrease in the enzymatic hydrolysis of the ATP and AMP is probably related to the diminished malignant characteristics caused by temozolomide treatment on the gliomas in vivo.

Efeitos dos medicamentos hipolipêmicos no perfil lipídico de população idosa de Porto Alegre, RS, Brasil / Effects of hypolipemic drugs on the lipidic profile of Porto Alegre, RS, Brasil in older population

O perfil lipídico pode estar relacionado com doenças crônico-degenerativas e suas complicações. Alguns dos medicamentos usados para controlar os níveis lipêmicos são estatinas e fibratos. O objetivo deste trabalho foi verificar o perfil lipídico da população idosa de Porto Alegre, RS, Brasil, que faz uso desses medicamentos. Foram coletadas amostras de sangue de 456 idosos e as dosagens foram realizadas através da metodologia química seca. Para análise estatística foram utilizados os testes Student e Qui-quadrado. Analisou-se o perfil lipídico de 22 homens e 51 mulheres que faziam uso de medicamentos hipolipêmicos e comparou-se esse perfil com o de 85 homens e 161 mulheres que não faziam uso destes. Os resultados demonstraram diferença significativa na classificação dos riscos e nos valores médios de colesterol total, LDL e triglicerídeos, nas idosas que usavam hipolipêmicos em relação às quenão os utilizavam. No entanto, para os homens, ocorreu uma diminuição significativa nos resultados de LDL, nos que faziam uso dos hipolipêmicos, apresentando valores controlados para todos os índices. É necessário um maior acompanhamento para a utilização correta dos medicamentos citados pelas pacientes idosas, a fim de se obter um melhor controle da lipemia e uma melhoria nas condições de saúde dessas pacientes.

The lipidic profile can be related to chronic degenerative diseases and their complications. Some of the drugs used to control the lipidic levels are statins and fibrates. The aim of the study was to verify the lipidic profile of the elderly population of Porto Alegre, RS, Brazil that makes use of these medicines. Blood samples were collected from 465 elderly and the dosages were determined by drought chemical methodology. For statistical analysis were used the Student t test and Chi-square test. There were examined the lipidic profile of 22 men and 51 women that made use of hypolipemic drugs and compared with 85 men and 161 women that did not use these. The results showed significant differences in the classification of risk and the average values of total cholesterol, LDL and triglycerides in the elderly that used hypolipemic in relation to those that did not use. However, for men there was a significant decrease in LDL results of those that made use of hypolipemic drugs, presenting controlled values for all indexes. It’s necessary a better monitoring for the correct use of the drugs mentioned by elderly women patients in order to get a better control of lipidic profile and an improvement in the health conditions of these patients.

Terapia anti-hipertensiva utilizada por pacientes idosos de Porto Alegre/RS, Brasil / Antihypertensive therapy used by elderly patients fron Porto Alegre/RS, Brasil

Objetivos: Descrever o perfil de utilização de medicamentos com ação no sistema cardiovascular, especialmente anti-hipertensivos, por idosos residentes na cidade de Porto Alegre. Métodos: Estudo transversal exploratório e observacional com base populacional, realizado em 2006, sobre a utilização qualitativa e quantitativa de medicamentos por pacientes idosos. O instrumento utilizado para a coleta de dados foi uma ficha de seguimento farmacológico. Resultados: Do total de 385 pacientes entrevistados, 62,3% utilizavam medicamentos com ação do sistema cardiovascular, sendo que destes, 86,3% utilizavam anti-hipertensivos. Entre os 35,3% pacientes que faziam uso de monoterapia, 38,4% utilizavam inibidores da enzima conversora de angiotensina (ECA) E 26% utilizavam beta-bloqueadores. Dos 207 pacientes em monoterapia ou terapia combinada de dois ou mais medicamentos, 59,4% utilizavam diuréticos e 51,2% inibidores da ECA. Conclusões: Os diuréticos, inibidores da ECA e betabloqueadores foram anti-hipertensivos mais utilizados. Muitas vezes o usuário comete erros na medicação, o que pode ser resolvido com uma assistência correta a esse paciente. Diante da prevalência da hipertenção entre os idosos, observa-se a necessidade de uma maior atenção dos profissionais de saúde a esses pacientes.

Study of enteroparasites infection frequency and chemotherapeutic agents used in pediatric patients in a community living in Porto Alegre, RS, Brazil

As parasitoses provocadas por protozoários ou helmintos patogênicos afetam mais de dois bilhões de pessoas no mundo. Considerando os problemas gerados por infecções parasitárias e a necessidade do uso correto dos medicamentos prescritos, o objetivo deste trabalho foi detectar a freqüência de infecção por enteroparasitos e o uso de agentes quimioterápicos em crianças moradoras na periferia de Porto Alegre, RS, Brasil. Foram analisadas noventa e seis crianças em idade pré-escolar, que realizaram o exame parasitológico de fezes e que fizeram uso de antiparasitários. A eficácia do tratamento foi avaliada pelo exame parasitológico repetido seis meses após o tratamento. O mesmo teste diagnóstico foi utilizado para avaliar a cura que foi definida como a ausência de ovos e cistos nas fezes. Das crianças estudadas, 79 (82,3 por cento) estavam infectadas com um ou mais parasitas, os mais prevalentes foram Ascaris lumbricoides, Trichuris trichiura e Giardia lamblia. Os antiparasitários mais utilizados foram mebendazol (86 por cento das prescrições) e metronidazol (30,3 por cento) de acordo com a prevalência da infecção. A porcentagem de cura das 79 crianças estudadas após 6 meses do tratamento foi 65,3 por cento para A. lumbricoides e 66,1 por cento para T. trichiura. Este estudo sugere que um programa de educação continuada voltado para a prevenção e tratamento das infecções parasitárias tem se mostrado uma ferramenta útil na erradicação destas patologias.