A cyclopalladated complex interacts with mitochondrial membrane thiol-groups and induces the apoptotic intrinsic pathway in murine and cisplatin-resistant human tumor cells

<p>Abstract</p> <p>Background</p> <p>Systemic therapy for cancer metastatic lesions is difficult and generally renders a poor clinical response. Structural analogs of cisplatin, the most widely used synthetic metal complexes, show toxic side-effects and tumor cell resistance. Recently, palladium complexes with increased stability are being investigated to circumvent these limitations, and a biphosphinic cyclopalladated complex {Pd₂[<it>S_(-)</it>C², N-dmpa]₂(μ-dppe)Cl₂} named C7a efficiently controls the subcutaneous development of B16F10-Nex2 murine melanoma in syngeneic mice. Presently, we investigated the melanoma cell killing mechanism induced by C7a, and extended preclinical studies.</p> <p>Methods</p> <p>B16F10-Nex2 cells were treated <it>in vitro </it>with C7a in the presence/absence of DTT, and several parameters related to apoptosis induction were evaluated. Preclinical studies were performed, and mice were endovenously inoculated with B16F10-Nex2 cells, intraperitoneally treated with C7a, and lung metastatic nodules were counted. The cytotoxic effects and the respiratory metabolism were also determined in human tumor cell lines treated <it>in vitro </it>with C7a.</p> <p>Results</p> <p>Cyclopalladated complex interacts with thiol groups on the mitochondrial membrane proteins, causes dissipation of the mitochondrial membrane potential, and induces Bax translocation from the cytosol to mitochondria, colocalizing with a mitochondrial tracker. C7a also induced an increase in cytosolic calcium concentration, mainly from intracellular compartments, and a significant decrease in the ATP levels. Activation of effector caspases, chromatin condensation and DNA degradation, suggested that C7a activates the apoptotic intrinsic pathway in murine melanoma cells. In the preclinical studies, the C7a complex protected against murine metastatic melanoma and induced death in several human tumor cell lineages <it>in vitro</it>, including cisplatin-resistant ones. The mitochondria-dependent cell death was also induced by C7a in human tumor cells.</p> <p>Conclusions</p> <p>The cyclopalladated C7a complex is an effective chemotherapeutic anticancer compound against primary and metastatic murine and human tumors, including cisplatin-resistant cells, inducing apoptotic cell death via the intrinsic pathway.</p

Bauru School of Dentistry Tele-Health League: an educational strategy applied to research, teaching and extension among applications in tele-health

Tele-health is more than an innovative alternative; it is an excellent tool that enables access to health and education in health, making it possible to minimize distances, optimize time and reduce costs. Based on these advantages, some Brazilian Universities have used these actions in strategies of education, research and extension, aiming at the application of Tele-health in Brazil. In that way, the Bauru School of Dentistry - University of São Paulo (FOB-USP) has applied the use of information and communication technologies in health by means of a "Tele-Health League" (TL), in order to diagnose, prevent and treat diseases, in addition to educate the population and health services. OBJECTIVE: The present study aims to introduce the characteristics of the Tele-Health League of FOB-USP, as well as the development of its projects. MATERIAL AND METHODS: The Tele-Health League consisted as a Diffusion Course approved by the Provost of Culture and Academic Extension of the University of São Paulo. It is composed as a large group enclosing professoriate coordinator, academician principal, contributing professors and league members, those, diversified between undergraduates students, graduated, health employees, technology and information areas. The participant members are evaluated by the presence frequency (minimum of 85%), and by the performance of tests and paperwork about the theoretical content provided. RESULTS: In four years of activities, the TLFOB-USP obtained a high satisfaction index (90%), an increased number of vacancies due to the interest to become a member, more commitment of the professors of the University and the accomplishment of association with other Brazilian leagues. It is emphasized that the approval percentage of the course results in approval from approximately half of its members. Also, it is important to identify and repair the causes related to the quitting of some members. CONCLUSIONS: The results showed that the TLFOB-USP members, adjoining to the professor's participants, develop projects in Tele-helth, in Tele-aid and Tele-education areas, thus resulting in the involvement of the University and the community

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013

Estimated costs of treatment of benign prostate hyperplasia in Brazil

INTRODUCTION: The treatment of benign prostate hyperplasia (BPH) presents 2 options: medical or surgical, and there are doubts about what is the best treatment since 80% of patients who undergo surgery become asymptomatic and 10 to 40% of those under medical regimen undergo surgery within a 5 years period. It is difficult to assess the actual costs of treating BPH in Brazil due to several factors, among them regional particularities and the scarcity of current statistical data. PATIENTS AND METHODS: Recently, in the Ribeirão Preto area, São Paulo, Brazil, the IPSS (International Prostatic Symptoms Score) and quality of life were verified in 934 volunteers. It was determined the percentage of individuals with ages ranging from 40 to 79 years with moderate symptoms (score 8-19) and with severe symptoms (score 20-35), values for which are indicated medical and surgical treatment, respectively, according to the Brazilian Society of Urology consensus on BPH. Data on Brazilian population in that age range were obtained from the Brazilian Institute of Geography and Statistics referent to the year of 2000. It was determined the number of patients, according to the criteria above, subjected to either one of the treatments mentioned. Surgical costs of prostate transurethral resection were researched according to Unified Health System - SUS tables (US$173) and of Brazilian Medical Society - AMB with a mean cost in 3 hospitals of US$ 933. Drug costs were calculated by the annual mean price (US$355) of 4 alpha-blockers (tamsulosin, alfuzosin, doxazosin and terazosin). RESULTS: The estimated population for medical treatment was 5,397,321 individuals, with a cost corresponding to US$ 1,916,489,055.00. The estimated population for surgical treatment was 2,040,299 men, what would represent a cost of US$353,291,204.00 based on the SUS table and of US$ 1,904,279,066.00 based on AMB with hospital expenses included. CONCLUSION: All theses facts induce us to predict that the treatment of BPH in a not-so-far future can become a public health problem for Brazilian society, since the current estimate would be, approximately, costs around 2.26 - 3.83 billion dollars, added by the yearly increase in the risk population (24.99%) for the group under medical treatment and over the non-operated amount of the surgical group

Antígeno MIB-1 em nefroblastomas MIB-1 antigen in nephroblastomas

Foram estudados 35 pacientes tratados com nefrectomia radical e quimioterapia, em 17 (48,5%) dos quais se associou também a radioterapia. A idade média dos pacientes foi de 38± 29 meses e o tempo de seguimento pós-operatório de 69± 66 meses. Óbito pela neoplasia ocorreu em 5 pacientes, todos com histologia favorável. As peças conservadas em formol ou blocos de parafina para imunhistoquímica com anticorpo MIB-1, método da avidina-biotina-peroxidase. Em 13/35 (37,1%) dos tumores a marcação para o MIB-1 foi positiva. As proporções respectivas de marcação para blastema, epitélio e estroma foram: 34,6%, 18,7% e 0%. Não houve diferença estatística entre a marcação imunohistoquímica e com o tipo histológico, estádio e sobrevida dos pacientes