Inibidores dos microtúbulos

Trabalho apresentado no Serviço de Oncologia do Hospital Prof. Doutor Fernando Fonseca, numa sessão de Farmaco-Oncologia, a 14/05/2014. As sessões eram destinadas à abordagem das diversas classes de citostáticos e outros fármacos usados no tratamento do cancro. Esta apresentação contempla a classe dos inibidores dos microtúbulos ou agentes anti- tubulina, abordando a natureza química bem como a farmacodinâmica e a farmacocinética dos compostos

Abordagem dos efeitos secundários dos inibidores tirosina cinase

Os slides abordam os diversos efeitos secundários dos inibidores tirosina cinase(fármacos anti-neoplásicos relativamente recentes na prática clínica) tendo em conta a sua apresentação clínica, o seu significado e a sua abordagem terapêutica

Cycling in São Paulo, Brazil (1997-2012): Correlates, time trends and health consequences

The purpose of the study was to describe cyclists and cycling trips, and to explore correlates, time trends and health consequences of cycling in São Paulo, Brazil from 1997 to 2012. Cross-sectional analysis using repeated São Paulo Household Travel Surveys (HTS). At all time periods cycling was a minority travel mode in São Paulo (1174 people with cycling trips out of 214,719 people). Poisson regressions for individual correlates were estimated using the entire 2012 HTS sample. Men were six times more likely to cycle than women. We found rates of bicycle use rising over time among the richest quartile but total cycling rates dropped from 1997 to 2012 due to decreasing rates among the poor. Harms from air pollution would negate benefits from physical activity through cycling only at 1997 air pollution levels and at very high cycling levels (≥ 9 h of cycling per day). Exposure-based road injury risk decreased between 2007 and 2012, from 0.76 to 0.56 cyclist deaths per 1000 person-hours travelled. Policies to reduce spatial segregation, measures to tackle air pollution, improvements in dedicated cycling infrastructure, and integrating the bicycle with the public transport system in neighborhoods of all income levels could make cycling safer and prevent more individuals from abandoning the cycling mode in São Paulo.THS acknowledges funding from the Brazilian Science without Borders Scheme (Process number: 200358/2014-6) and the Sao Paulo Research Foundation (Process number: 2012/08565-4). ACD received a postdoctoral research fellowship from the Brazilian National Council for Scientific and Technological Development (249038/2013-7). MT and JW: The work was undertaken by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust (MR/K023187/1), under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged

Impact of Renal Dysfunction on Liver Transplantation: a Retrospective Study in 708 Orthotopic Liver Transplant Recipients

Renal dysfunction often complicates the course of orthotopic liver transplant recipients and is associated with increased morbid -mortality. The aims of this study were to determine the incidence of chronic renal disease and its impact on patient survival. Clinical data included age, gender and weight,aetiology of hepatic failure, presence of diabetes,hypertension, hepatitis B and C infection, renal dysfunction pretransplant and immunosuppression. Laboratory data included serum creatinine at days 1, 7, 21, month 6, 12 and yearly. The glomerular filtration rate was determined by Cockcroft-Gault equation. We studied retrospectively from September 1992 to March 2007 708 orthotopic liver transplant recipients. Mean age 44±12.6 years, 64% males, 17% diabetic, 18.8% hypertensive, 19.9% with hepatitis C and 3.8% hepatitis B. Renal dysfunction pretransplant was known in 21.6%. Mean follow-up was 3.6 years. Mean transplant survival 75% at 12 months. 154 patients died. Univariate and multivariate analyses were performed and a p<0.05 was considered significant. Acute kidney injury occurred in 33.2%. Chronic kidney disease stage 3 was observed in 34.3%,stage 4 in 6.2% and stage 5 in 5.1%. At the time of this study, 46.4% were on Cyclosporine A, 44.7% on tacrolimus and 8.9% on sirolimus. Using multivariate analysis, renal dysfunction was correlated with renal dysfunction pre -orthotopic liver transplant (p<0.001), acute kidney injury (p<0.001), haemodialysis development (p<0.001), and inversely correlated with the use of mycophenolate mophetil (p<0.001); mortality was positively correlated with renal dysfunction pretransplant (p=0.03),chronic kidney disease stage 4 (p=0.001), chronic kidney disease stage 5 (p<0.001) and inversely correlated with the use of tacrolimus (p=0.006). In conclusion orthotopic liver transplant recipients are disposed to renal complications that have a negative impact on survival of these patients

Orthotopic Liver Transplantation in Familial Amyloidotic Polyneuropathy Is Associated with Long-Term Progression of Renal Disease

Orthotopic liver transplantation has become the treatment of choice for familial amyloidotic polyneuropathy. The aims of this study were to evaluate the renal complications post orthotopic liver transplantation in familial amyloidotic polyneuropathy and their impact. We retrospectively studied 185 recipients who underwent 217 orthotopic liver transplants. Mean age 36.8±9.5 years, 59% males, 14.3% with renal dysfunction pre orthotopic liver transplantation. Mean follow-up 3.6±3.7 years. Thirty-two patients died. Univariate and multivariate analysis were performed, and p<0.05 was considered significant. Acute kidney injury occurred in 57 patients and renal replacement therapy was needed in 16/57. In multivariate analysis, acute kidney injury was correlated with development of chronic kidney disease (p<0.001). Relating to development of chronic kidney disease, 23.5% had progress to stage 3, 6% to stage 4 and 5.1% to stage 5d. According to Spearmen correlation, risk factors for chronic kidney disease development were age (p<0.001), renal dysfunction pre orthotopic liver transplantation (p<0.001) and acute kidney injury post orthotopic liver transplantation (p<0.001). Mortality was correlated with age (p<0.001), retransplantation need (p=0.004), renal dysfunction pre orthotopic liver transplantation (p<0.001), acute kidney injury post orthotopic liver transplantation (p=0.04), and chronic kidney disease stage 5 (p<0.001). Using binary regression, mortality was correlated with chronic kidney disease development (p=0.02). In conclusion, familial amyloidotic polyneuropathy patients are disposed to renal complications that have a negative impact on the survival of these patients

Dhvar5-chitosan nanogels and their potential to improve antibiotics activity

Infection is one of the main causes of orthopedic implants failure, with antibiotic-resistant bacteria playing a crucial role in this outcome. In this work, antimicrobial nanogels were developed to be applied in situ as implant coating to prevent orthopedic-device-related infections. To that regard, a broad-spectrum antimicrobial peptide, Dhvar5, was grafted onto chitosan via thiol-norbornene "photoclick" chemistry. Dhvar5-chitosan nanogels (Dhvar5-NG) were then produced using a microfluidic system. Dhvar5-NG (1010 nanogels (NG)/mL) with a Dhvar5 concentration of 6 μg/mL reduced the burden of the most critical bacteria in orthopedic infections - methicillin-resistant Staphylococcus aureus (MRSA) - after 24 h in medium supplemented with human plasma proteins. Transmission electron microscopy showed that Dhvar5-NG killed bacteria by membrane disruption and cytoplasm release. No signs of cytotoxicity against a pre-osteoblast cell line were verified upon incubation with Dhvar5-NG. To further explore therapeutic alternatives, the potential synergistic effect of Dhvar5-NG with antibiotics was evaluated against MRSA. Dhvar5-NG at a sub-minimal inhibitory concentration (109 NG/mL) demonstrated synergistic effect with oxacillin (4-fold reduction: from 2 to 0.5 μg/mL) and piperacillin (2-fold reduction: from 2 to 1 μg/mL). This work supports the use of Dhvar5-NG as adjuvant of antibiotics to the prevention of orthopedic devices-related infections.The authors B. Costa, P.M. Alves and D. R. Fonseca would like to thank the Portuguese Foundation for Science and Technology (FCT) (Refs. SFRH/BD/147027/2019, SFRH/BD/145471/2019 and SFRH/BD/146890/2019), FCT/MCTES (Ref. CEECIND/01921/2017). C. Monteiro Thanks FCT by her contract-program (art. 23 of Law no. 57/2016 & 57/2017). Paula Gomes thanks FCT/MCTES for financial support to the LAQV-REQUIMTE Research Unit (UIDB/50006/2020; DOI 10.54499/UIDB/50006/2020) through national funds. A. Gomes thanks FCT/MCTES for Junior Researcher Contract 2022.08044.CEECIND/CP1724/CT0004 (DOI:10.54499/2022.08044.CEECIND/CP1724/CT0004). M.C.L. Martins also acknowledges FCT (LA/P/0070/2020) and MOBILIsE Project, which has received funding from the European Union’’s Horizon 2020 research and innovation program under grant agreement no. 951723

Impact of RIFLE Classification in Liver Transplantation

Acute renal failure (ARF) is common after orthotopic liver transplantation (OLT). The aim of this study was to evaluate the prognostic value of RIFLE classification in the development of CKD, hemodialysis requirement, and mortality. Patients were categorized as risk (R), injury (I) or failure (F) according to renal function at day 1, 7 and 21. Final renal function was classified according to K/DIGO guidelines. We studied 708 OLT recipients, transplanted between September 1992 and March 2007; mean age 44 +/- 12.6 yr, mean follow-up 3.6 yr (28.8% > or = 5 yr). Renal dysfunction before OLT was known in 21.6%. According to the RIFLE classification, ARF occurred in 33.2%: 16.8% were R class, 8.5% I class and 7.9% F class. CKD developed in 45.6%, with stages 4 or 5d in 11.3%. Mortality for R, I and F classes were, respectively, 10.9%, 13.3% and 39.3%. Severity of ARF correlated with development of CKD: stage 3 was associated with all classes of ARF, stages 4 and 5d only with severe ARF. Hemodialysis requirement (23%) and mortality were only correlated with the most severe form of ARF (F class). In conclusion, RIFLE classification is a useful tool to stratify the severity of early ARF providing a prognostic indicator for the risk of CKD occurrence and death