Interaction between gemcitabine and topotecan in human non-small-cell lung cancer cells: effects on cell survival, cell cycle and pharmacogenetic profile

The pyrimidine analogue gemcitabine is an established effective agent in the treatment of non-small-cell lung cancer (NSCLC). The present study investigates whether gemcitabine would be synergistic with the topoisomerase I inhibitor topotecan against the NSCLC A549 and Calu-6 cells. Cells were treated with gemcitabine and topotecan for 1 h and the type of drug interaction was assessed using the combination index (CI). Cell cycle alterations were analysed by flow cytometry, while apoptosis was examined by the occurrence of DNA internucleosomal fragmentation, nuclear condensation and caspase-3 activation. Moreover, the possible involvement of the PI3K-Akt signalling pathway was investigated by the measurement of Akt phosphorylation. Finally, quantitative, real-time PCR (QRT-PCR) was used to study modulation of the gemcitabine-activating enzyme deoxycytidine kinase (dCK) and the cellular target enzyme ribonucleotide reductase (RR). In results, it was found that simultaneous and sequential topotecan → gemcitabine treatments were synergistic, while the reverse sequence was antagonistic in both cell lines. DNA fragmentation, nuclear condensation and enhanced caspase-3 activity demonstrated that the drug combination markedly increased apoptosis in comparison with either single agent, while cell cycle analysis showed that topotecan increased cells in S phase. Furthermore, topotecan treatment significantly decreased the amount of the activated form of Akt, and enhanced the expression of dCK (+155.0 and +115.3% in A549 and Calu-6 cells, respectively), potentially facilitating gemcitabine activity. In conclusion, these results indicate that the combination of gemcitabine and topotecan displays schedule-dependent activity in vitro against NSCLC cells. The gemcitabine → topotecan sequence is antagonistic while drug synergism is obtained with the simultaneous and the sequential topotecan → gemcitabine combinations, which are associated with induction of decreased Akt phosphorylation and increased dCK expression

estudos artísticos

A revista Gama prossegue o aprofundamento da sua linha editorial específica e dentro do projeto mais alargado de desafiar criadores a debaterem e apresentar a obra de outros criadores, dentro do espaço descentrado que é o universo dos idiomas ibéricos. Trata-se de, dentro deste tema mais abrangente, revisitar arquivos, autores de épocas um pouco recuadas, de resgatar do esquecimento o património que existe e urge apresentar, discutir, colocar em ação, fazer funcionar, pela voz dos artistas. A arte necessita de ser ativada por intermédio do pensamento, e com ele, do discurso. Há vozes silenciosas que aguardam olhos, ouvidos, inquietações, deslumbramentos. Quando uma peça é descoberta é como se voltasse a ser feita: esse é o paradoxo do documento. A arte é vestígio e ao mesmo tempo universalidade, eternidade. É local e total. É sempre, em simultâneo, sem contradição, facto e possibilidade, presença e ausência. Os vinte e quatro artigos apresentados neste número cinco da Revista Gama oferecem outros tantos pontos de vista sobre os discursos artísticos. Recupera-se obra desconhecida, mostram-se obras, descobrem-se autores desaparecidos. Aqui a arte depositou-se, precipitou-se, tornou-se visível ao resgate. O resgate, operação de amor, é feito por artistas. Os públicos estão no futuro, à nossa espera.info:eu-repo/semantics/publishedVersio

Auto-retrato e auto-representação

info:eu-repo/semantics/publishedVersio

Lo sbrigliamento delle ulcere cutanee

The aim of this study is to review different methods of debridement in chronic wounds and to identify the evidence of debriding agents in wound healing. Debridement is an essential part of the tissue repair process and is defined as the removal of devitalized tissue from the wound bed. The accumulation of this tissue is regarded to prevent or delay granulation and epithelialization. Debridement techniques are divided into mechanical and non-mechanical methods on the basis of the physical peculiarities of the means employed and into selective and non-selective methods regarding the preservation or not of vital tissue from the wound bed. Advantages and disadvantages of each procedure are taken in to account to select the best form of debridement for each type of chronic wound. Surgical debridement is the most aggressive form and the more rapid compared to other techniques. It is essential to prevent infection and to remove dry thick eschars mainly in pressure ulcers. Autolytic debridement is the most easy and well tolerated from the patient and it is obtained through the use of occlusive dressings. Other forms of debridement such as the larva-therapy were used in the past and today have been reconsidered as useful and safe methods. The enzymatic and wet to dry debridements are the most common methods in our country and this is mainly due to the availability of these products. Chronic wounds are often contaminated with devitalized tissue and foreign material, which represent a barrier to cells migration and a source of infection. Selection of the debridement technique must consider the patient compliance, the wound size, the amount of exudate and the skill of the operator

Valutazione clinica e strumentale dell'attività terapeutica di un vasoprotettore contenente vitamina PP,vitamina C ed estratti fitoterapici titolati in escina,bromelina,antocianosidi nella cura delle ulcere

Background. Chronic leg ulcers due to venous insufficiency represent a significant burden for the national sanitary system. Although the role of venous hypertension as a key pathogenetic factor of this lesion is clear, several microcirculatory mechanisms involved in the tissue repair process remain to be clarified. The purpose of this study was to evaluate the efficacy and tolerability of a vasoactive drug for the treatment of varicose leg ulcers. Methods. The study was a prospective randomized trial lasting eight weeks. Twenty patients matched for sex, age, wound dimensions and with clinical and instrumental evidence of chronic venous insufficiency were enrolled in this study. Patients attended a weekly consultation at the outpatients clinic for chronic leg ulcers of the Department of Dermatology at the University of Pisa and they were randomized into two groups according to treatment: G1 (n=10) vasoactive drug, occlusive dressing, elastic bandage, G2 (n=10) occlusive dressing, elastic bandage. During the study, subjective parameters were evaluated: intensity of pain, paresthesia, heaviness and objective parameters: intensity of oedema, wound area, transcutaneous tissue gas monitoring (O2 - CO2). Results. At the end of the study a marked reduction of subjective symptoms such as pain and paresthesia was observed with an increase of oxygen tissue perfusion in the G1 group compared to the G2 group. No significant differences were observed in the two groups about the remaining parameters investigated. Conclusions. The drug investigated in this study showed a good tolerability and efficacy in weakening the clinical symptoms related to venous insufficiency. The positive effect of the vasoactive drug on transcutaneous oxygen tension confirms a direct action on the microcirculatory system, which could positively modulate the tissue repair process

The "phone and mail" system in a teledermatology service for chronic psychiatric patients

AIM: We aimed to test a new teledermatologic method that permits to match a high level of diagnostic accuracy, comparable with or higher to that of the "Store and Forward" method, with the highest handiness, comparable to that achievable with a video call, without suffering from the limitations of the two methods. METHODS: We used latest-generation cell phones with a HSDPA network broad-band internet access system for video calling and for sending via e-mail high-definition images, chosen by the specialist-at-a-distance during the video call, in times comparable to those achievable with fixed-wired access systems. We tested the diagnostic reliability, the compliance and the efficacy of the method. RESULTS: We found a significant concordance both between direct and via video call description of the objective signs and between direct and on high definition image description. The Spearman Rank showed a higher correlation between direct observation and high definition image observation than between direct and via video call observation: this last finding matched the experimenters' subjective experience. The compliance was positive and the efficacy comparable with the ambulatorial follow-up. CONCLUSION: In conclusion, the "Phone and Mail" method can be seen as being capable of joining together the necessary diagnostic precision and effectiveness with a high degree of practicality and simplicity, thanks to the ease of use of the cell phone, within the reach of everybody, to the ubiquity of its utilization, to the allowed rapidity of diagnosis, practically in real time, and to the low cost of the system

Thalidomide in chronic sarcoidosis: two-year follow-up

Sarcoidosis Vasculitis and Diffuse Lung Disease