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1.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38960062

RESUMO

INTRODUCTION AND OBJECTIVES: Long-term use of an indwelling catheter is associated with complications such as catheter encrustation and infection. Canoxidin® is a novel oral treatment that can potentially prevent catheter encrustation, as it contains a urine acidifier and a combination of two crystallization inhibitors. This study aimed to evaluate the effects of Canoxidin® on catheter encrustation in patients with indwelling Foley catheters. PATIENTS AND METHODS: This was a single-center, double-blind, randomized, placebo-controlled study. Neuro-urology patients aged ≥18 years with an indwelling catheter (urethral or suprapubic) were randomized to treatment consisting of either Canoxidin® or placebo for one month. Foley catheters (two per patient, one before treatment and one after treatment) were removed for analysis of the presence and degree of encrustation. RESULTS: A total of 40 patients were enrolled and randomized, 28 of whom had analyzable catheters (13 assigned to Canoxidin® and 15 assigned to placebo). The patients had a mean age of 51.8 years, and eight (28.6%) were female. Two patients (13.3%) in the placebo group and eight patients (61.5%) in the Canoxidin® group experienced an improvement (less encrustation). There was a significant association between Canoxidin® and improvement (odds ratio: 10.4, 95% confidence interval: 1.6 to 66.9, P = 0.016). No adverse effects attributable to the treatment were reported. CONCLUSIONS: The overall rate of catheter encrustation was high among those with indwelling Foley catheters. One-month treatment with Canoxidin® reduced the formation of these encrustations, with an excellent short-term safety profile.

3.
Sustain Sci ; 17(5): 2013-2029, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340343

RESUMO

Forests are key components of European multifunctional landscapes and supply numerous forest ecosystem services (FES) fundamental to human well-being. The sustainable provision of FES has the potential to provide responses to major societal challenges, such as climate change, biodiversity loss, or rural development. To identify suitable strategies for the future sustenance of FES, we performed a solution scanning exercise with a group of transdisciplinary forest and FES experts from different European regions. We identified and prioritized fifteen major challenges hindering the balanced provision of multiple FES and identified a series of potential solutions to tackle each of them. The most prominent challenges referred to the increased frequency and impacts of extreme weather events and the normative mindset regarding forest management. The respective solutions pointed to the promotion of forest resilience via climate-smart forestry and mainstreaming FES-oriented management through a threefold strategy focusing on education, awareness raising, and networking. In a subsequent survey, most solutions were assessed as highly effective, transferable, monitorable, and with potential for being economically efficient. The implementation of the solutions could have synergistic effects when applying the notion of leverage points. Seven emerging pathways towards the sustainable supply of FES have been identified. These pathways build on each other and are organized based on their potential for transformation: (1) shifting forest management paradigms towards pluralistic ecosystem valuation; (2) using integrated landscape approaches; (3) increasing forest resilience; (4) coordinating actions between forest-related actors; (5) increasing participation in forest planning and management; (6) continuous, open, and transparent knowledge integration; and (7) using incentive-based instruments to support regulating and cultural FES. These pathways can contribute to the implementation of the new EU Forestry Strategy to support the balanced supply of multiple FES. Supplementary Information: The online version contains supplementary material available at 10.1007/s11625-022-01111-4.

4.
Sustain Sci ; 16(2): 703-708, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33686348

RESUMO

Enduring sustainability challenges requires a new model of collective leadership that embraces critical reflection, inclusivity and care. Leadership collectives can support a move in academia from metrics to merits, from a focus on career to care, and enact a shift from disciplinary to inter- and trans-disciplinary research. Academic organisations need to reorient their training programs, work ethics and reward systems to encourage collective excellence and to allow space for future leaders to develop and enact a radically re-imagined vision of how to lead as a collective with care for people and the planet. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11625-021-00909-y.

5.
Sci Rep ; 10(1): 15166, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938968

RESUMO

Holm oak trees (Quercus ilex L.) mortality is increasing worryingly in the Mediterranean area in the last years. To a large degree this mortality is caused by the oomycete Phytophthora spp., which is responsible for forest decline and dieback in evergreen oak forest areas of the southwestern Iberian Peninsula. This study is based on the possibility of applying chemical elicitors or filtered oomycete extracts to holm oak somatic embryos (SE) in order to induce epigenetic memory, priming, that may increase tolerance to the pathogen in future infections. To this end, we first examined the effect of priming treatments on SE development and its oxidative stress state, to avoid elicitors that may cause damage to embryogenic tissues. Both, the sterile oomycete extracts and the chemical elicitor methyl jasmonate (MeJA) did not produce any detrimental effect on SE growth and development, unlike the elicitors benzothiadiazole (BTH) and p-aminobenzoic acid (PABA) that reduced the relative weight gain and resulted in necrotic and deformed SE when were applied at high concentrations (25 µM BTH or 50 µM PABA) in accordance with their high malondialdehyde content. No significant differences among elicitation treatments were found in dual culture bioassays, although those SEs elicited with 50 µM MeJA increased H2O2 production after challenged against active oomycete indicating the activation of stress response. Since this elicitation treatment did not produce any adverse effect in the embryogenic process we suggest that could be used in further priming experiments to produce holm oak plants adapted to biotic stress.


Assuntos
Phytophthora/patogenicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Quercus/embriologia , Quercus/microbiologia , Ácido 4-Aminobenzoico/toxicidade , Acetatos/farmacologia , Ciclopentanos/farmacologia , Florestas , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Oxilipinas/farmacologia , Phytophthora/química , Proteínas/farmacologia , Quercus/efeitos dos fármacos , Sementes/efeitos dos fármacos , Sementes/embriologia , Sementes/metabolismo , Espanha , Tiadiazóis/toxicidade
6.
Cardiovasc Diabetol ; 17(1): 12, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29325553

RESUMO

BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG). Hearts and plasma were isolated for biochemical approaches. Cultured cardiomyocytes were examined for receptor distribution after incretin stimulation in high fatty acid or high glucose media. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18FDG assimilation and diastolic dysfunction. However, sitagliptin improved hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced 18FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal translocation of the glucose transporter-4 (Glut4), in detriment of the fatty acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal translocation were also increased after GLP-1 stimulation in high-fatty acid incubated cardiomyocytes. PI3K/Akt and AMPKα were involved in this response. Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar effects. CONCLUSIONS: Besides of its anti-hyperglycemic effect, sitagliptin-enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by shifting fatty acid to glucose utilization in the cardiomyocyte, and thus, improving cardiac efficiency and reducing lipolysis.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Inibidores da Dipeptidil Peptidase IV/farmacologia , Metabolismo Energético/efeitos dos fármacos , Ácidos Graxos/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Transportador de Glucose Tipo 4/metabolismo , Incretinas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Fosfato de Sitagliptina/farmacologia , Animais , Glicemia/metabolismo , Células Cultivadas , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/sangue , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Transportador de Glucose Tipo 4/genética , Masculino , Camundongos , Miócitos Cardíacos/metabolismo , Transporte Proteico , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
7.
Appl Radiat Isot ; 119: 28-35, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27829184

RESUMO

The ion exchange properties of some tin and titanium oxides with potential application in the development of a 68Ge/68Ga generator were determined. The best potential candidates, SnO2 and calcined SnO2, were further characterized by powder X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Brunauer-Emmett-Teller (BET) surface area analysis and its radiation stability was also determined. Two 68Ge/68Ga pilot generators (1.85MBq) based on SnO2 and calcined SnO2 were developed and evaluated over 100 and 200 elution cycles respectively, using as eluent different concentrations of HCl. The generator based on calcined SnO2 showed higher 68Ga elution yield and lower 68Ge content in the eluate (75-80% and <3×10-3% respectively, 1-2M HCl) than the generator based on unheated SnO2 (60-65% and <1×10-1% respectively, 1-2M HCl). Nano-crystalline calcined SnO2 proved to be a promising sorbent; therefore it should be considered as an attractive candidate to develop 68Ge/68Ga generators to produce gallium-68 for biomedical purposes.

8.
PLoS One ; 11(7): e0158634, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27462980

RESUMO

BACKGROUND: A critical challenge in the management of Glioblastoma Multiforme (GBM) tumors is the accurate diagnosis and assessment of tumor progression in a noninvasive manner. We have identified Membrane-type 1 matrix metalloproteinase (MT1-MMP) as an attractive biomarker for GBM imaging since this protein is actively involved in tumor growth and progression, correlates with tumor grade and is closely associated with poor prognosis in GBM patients. Here, we report the development of an immunoPET tracer for effective detection of MT1-MMP in GBM models. METHODS: An anti-human MT1-MMP monoclonal antibody (mAb), LEM2/15, was conjugated to p-isothiocyanatobenzyl-desferrioxamine (DFO-NCS) for 89Zr labeling. Biodistribution and PET imaging studies were performed in xenograft mice bearing human GBM cells (U251) expressing MT1-MMP and non-expressing breast carcinoma cells (MCF-7) as negative control. Two orthotopic brain GBM models, patient-derived neurospheres (TS543) and U251 cells, with different degrees of blood-brain barrier (BBB) disruption were also used for PET imaging experiments. RESULTS: 89Zr labeling of DFO-LEM2/15 was achieved with high yield (>90%) and specific activity (78.5 MBq/mg). Biodistribution experiments indicated that 89Zr-DFO-LEM2/15 showed excellent potential as a radiotracer for detection of MT1-MMP positive GBM tumors. PET imaging also indicated a specific and prominent 89Zr-DFO-LEM2/15 uptake in MT1-MMP+ U251 GBM tumors compared to MT1-MMP- MCF-7 breast tumors. Results obtained in orthotopic brain GBM models revealed a high dependence of a disrupted BBB for tracer penetrance into tumors. 89Zr-DFO-LEM2/15 showed much higher accumulation in TS543 tumors with a highly disrupted BBB than in U251 orthotopic model in which the BBB permeability was only partially increased. Histological analysis confirmed the specificity of the immunoconjugate in all GBM models. CONCLUSION: A new anti MT1-MMP-mAb tracer, 89Zr-DFO-LEM2/15, was synthesized efficiently. In vivo validation showed high-specific-contrast imaging of MT1-MMP positive GBM tumors and provided strong evidence for utility of MT1-MMP-targeted immunoPET as an alternate to nonspecific imaging of GBM.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Metaloproteinase 14 da Matriz/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Animais , Anticorpos Monoclonais/imunologia , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/enzimologia , Linhagem Celular Tumoral , Glioblastoma/enzimologia , Humanos , Metaloproteinase 14 da Matriz/imunologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Prognóstico , Microtomografia por Raio-X
9.
Oncogene ; 31(9): 1073-85, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21841826

RESUMO

5-Fluorouracil (5-FU), together with other drugs such as oxaliplatin, is one of the most important pharmacological agents in the treatment of colorectal cancer. Although mitogen-activated protein kinases (MAPKs) have been extensively connected with resistance to platinum compounds, no role has been established in 5-FU resistance. Here we demonstrate that p38MAPK activation is a key determinant in the cellular response to 5-FU. Thus, inhibition of p38MAPKα by SB203580 compound or by short-hairpin RNA interference-specific knockdown correlates with a decrease in the 5-FU-associated apoptosis and chemical resistance in both HaCaT and HCT116 cells. Activation of p38MAPK by 5-FU was dependent on canonical MAP2K, MAPK kinase (MKK)-3 and MKK6. In addition, ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR) showed a redundancy of function for the final activation of p38MAPK. Resistance associated with p38MAPK inhibition correlates with an autophagic response that was mediated by a decrease in p53-driven apoptosis, without effect onto p53-dependent autophagy. Moreover, the results with colorectal cancer-derived cell lines with different p53 status and patterns of resistance to 5-FU suggest that de novo and acquired resistance was controlled by similar mechanisms. In summary, our data demonstrate a critical role for the p38MAPK signaling pathway in the cellular response to 5-FU by controlling the balance between apoptosis and autophagy.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Apoptose , Autofagia , Fluoruracila/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Mutadas de Ataxia Telangiectasia , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Ativação Enzimática/efeitos dos fármacos , Células HCT116 , Células HT29 , Humanos , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/metabolismo
10.
Trauma (Majadahonda) ; 22(4): 264-271, oct.-dic. 2011. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-93859

RESUMO

Objetivo: Introducir la estimulación eléctrica del nervio pudendo como un procedimiento capaz de tratar la hiperactividad neurogénica del detrusor en un contexto hospitalario y domiciliario. Pacientes y Métodos: Para el primer estudio (Programa de autoestimulación en ambiente domiciliario) se reclutaron 11 pacientes. La duración del protocolo fue de una semana e incluía dos urodinámicas, una al principio y otra al final del proceso. En el segundo protocolo se incluyeron doce pacientes (Estimulación eléctrica mediante EMG del nervio dorsal del pene/clítoris) donde se realizaron dos urodinámicas sucesivas, la primera sin y la segunda con estimulación. En los dos estudios se valoró la capacidad cistométrica. En el primer estudio, a los pacientes se les pedía que rellenaran un diario miccional. Resultados: Tanto para el primero como para el segundo estudio, los pacientes mostraron un aumento significativo de las capacidades cistométricas en las urodinámicas posteriores comparadas con las iniciales (p=0,045) (p=0,002). El volumen medio de micción diaria se incrementó conforme avanza la estimulación (p=0,035). Conclusión: La viabilidad y los resultados globalmente positivos de los estudios prueban que la estimulación eléctrica del nervio pudendo puede ser una opción para el tratamiento de la hiperactividad neurogénica del detrusor (AU)


Objetive: To introduce the electrical stimulation of the pudendal nerve as an effective procedure to treat neurogenic detrusor overactivity in both hospital and home settings. Patients and Methods: For this purpose, two studies were designed and performed. Eleven patients were recruited in the first study (Autostimulation program in home setting). The duration of the protocol was one week and it included two urodynamics, first at baseline and the second at the end of the study. In the second study (EMG electrical stimulation of the dorsal penile/clitoral nerve), twelve patients were included. Patients underwent two successive urodynamics, first without and second with electrical stimulation. In both studies, cystometric capacities were used to assess objectively the outcome of the treatment. In the first study, patients were asked to fill a bladder diary. Results: In both first and second studies, patients show an statistically significant improvement of the cystometric capacities in posterior urodynamics compared to baseline urodynamics (p=0.045 and p=0.002, respectively). Mean micturition volume per day increased significantly as long as stimulation days advanced (p=0.035). Conclusion: The feasibility and the globally positive outcomes of t both studies show that the stimulation of the pudendal nerve can be an option to the treatment of the neurogenic detrusor overactivity (AU)


Assuntos
Humanos , Masculino , Estimulação Elétrica/métodos , Bexiga Urinária Hiperativa/reabilitação , Bexiga Urinária Hiperativa , Urodinâmica/fisiologia , Eletromiografia/métodos , Eletromiografia , Estimulação Elétrica/instrumentação , Bexiga Urinaria Neurogênica/reabilitação , Bexiga Urinaria Neurogênica , Autoestimulação/fisiologia , Autoestimulação/efeitos da radiação , Raízes Nervosas Espinhais/efeitos da radiação , Raízes Nervosas Espinhais
11.
Cell Death Dis ; 1: e52, 2010 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-21364657

RESUMO

During partial hepatectomy, ischemia-reperfusion (I/R) is commonly applied in clinical practice to reduce blood flow. Steatotic livers show impaired regenerative response and reduced tolerance to hepatic injury. We examined the effects of tauroursodeoxycholic acid (TUDCA) and 4-phenyl butyric acid (PBA) in steatotic and non-steatotic livers during partial hepatectomy under I/R (PH+I/R). Their effects on the induction of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress were also evaluated. We report that PBA, and especially TUDCA, reduced inflammation, apoptosis and necrosis, and improved liver regeneration in both liver types. Both compounds, especially TUDCA, protected both liver types against ER damage, as they reduced the activation of two of the three pathways of UPR (namely inositol-requiring enzyme and PKR-like ER kinase) and their target molecules caspase 12, c-Jun N-terminal kinase and C/EBP homologous protein-10. Only TUDCA, possibly mediated by extracellular signal-regulated kinase upregulation, inactivated glycogen synthase kinase-3ß. This is turn, inactivated mitochondrial voltage-dependent anion channel, reduced cytochrome c release from the mitochondria and caspase 9 activation and protected both liver types against mitochondrial damage. These findings indicate that chemical chaperones, especially TUDCA, could protect steatotic and non-steatotic livers against injury and regeneration failure after PH+I/R.


Assuntos
Retículo Endoplasmático/metabolismo , Fígado Gorduroso/cirurgia , Hepatectomia , Fígado/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Animais , Caspase 12/metabolismo , Citocromos c/metabolismo , Fígado Gorduroso/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Proteínas de Choque Térmico/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Mitocôndrias/metabolismo , Fenilbutiratos/farmacologia , Ratos , Ratos Zucker , Traumatismo por Reperfusão/metabolismo , Ácido Tauroquenodesoxicólico/farmacologia , Resposta a Proteínas não Dobradas , Canais de Ânion Dependentes de Voltagem/metabolismo
12.
Clin Transl Oncol ; 11(3): 172-7, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19293055

RESUMO

PURPOSE: The aim of this study was to determine the feasibility, concerning compliance to protocol and recommended clinical practice guidelines, as well as efficacy results of multidisciplinary treatment (surgery, radiotherapy and chemotherapy) of resectable rectal cancer in a third-level hospital devoid of radiotherapy and clinical oncology units. PATIENTS AND METHODS: A retrospective, single-institution analysis was completed for 45 consecutive patients diagnosed with resectable rectal cancer who entered an officially proposed multidisciplinary treatment protocol from October 1998 to September 2003. Adequacy of patient inclusion, according to clinical stage, was reviewed. Neoadjuvant radiotherapy schedule, surgery procedures and adjuvant chemotherapy indication were assessed. All treatment time intervals were analysed. Finally, efficacy results are discussed and contextualised by comparison with results of clinical trials which support this treatment strategy. RESULTS: According to an independent board review, 3 patients (6.7%) with stage I rectal cancer, 31 patients (68.9%) with stage II and 11 patients (24.4%) with stage III rectal cancer were included. Radiotherapy dosage, volume and schedule were as planned. Median time from diagnosis to start of radiotherapy was 26.36 days (24.26- 28.57; CI 95%). Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Median time from start of radiotherapy to surgery was 15.67 days (14.47-16.87; CI 95%). Median time from completion of radiotherapy to surgery was 10.67 days (9.53-11.81; CI 95%). Most of the patients underwent low anterior resection [23 patients (51.2%)] and abdominoperineal resection [16 patients (35.6%)]. Correlation between clinical and pathologic staging was as expected. Twenty-nine patients (64.4%) of the 45 that were initially included started adjuvant chemotherapy. A statistically significant relationship between pathologic stage (grouped I-II vs. III) and the use of adjuvant chemotherapy was found (p=0.033; chi-square test). Radiotherapy- and chemotherapy-induced toxicity did not differ from that previously reported. With a median follow-up of 65.46 months, a total of 10 recurrences have been diagnosed, all of them in stage III patients. Overall survival rate at five years was 76% for the complete population included. CONCLUSION: Multidisciplinary treatment of resectable rectal cancer in a third-level hospital is feasible. Although efficacy results are comparable to those previously reported in the literature, further improvements in clinical staging as well as in adjuvant chemotherapy indication are desirable.


Assuntos
Neoplasias Retais/terapia , Terapia Combinada , Humanos , Estudos Longitudinais , Estadiamento de Neoplasias , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Taxa de Sobrevida
13.
Clin. transl. oncol. (Print) ; 11(3): 172-177, mar. 2009. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-123597

RESUMO

PURPOSE: The aim of this study was to determine the feasibility, concerning compliance to protocol and recommended clinical practice guidelines, as well as efficacy results of multidisciplinary treatment (surgery, radiotherapy and chemotherapy) of resectable rectal cancer in a third-level hospital devoid of radiotherapy and clinical oncology units. PATIENTS AND METHODS: A retrospective, single-institution analysis was completed for 45 consecutive patients diagnosed with resectable rectal cancer who entered an officially proposed multidisciplinary treatment protocol from October 1998 to September 2003. Adequacy of patient inclusion, according to clinical stage, was reviewed. Neoadjuvant radiotherapy schedule, surgery procedures and adjuvant chemotherapy indication were assessed. All treatment time intervals were analysed. Finally, efficacy results are discussed and contextualised by comparison with results of clinical trials which support this treatment strategy. RESULTS: According to an independent board review, 3 patients (6.7%) with stage I rectal cancer, 31 patients (68.9%) with stage II and 11 patients (24.4%) with stage III rectal cancer were included. Radiotherapy dosage, volume and schedule were as planned. Median time from diagnosis to start of radiotherapy was 26.36 days (24.26- 28.57; CI 95%). Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Median time from start of radiotherapy to surgery was 15.67 days (14.47-16.87; CI 95%). Median time from completion of radiotherapy to surgery was 10.67 days (9.53-11.81; CI 95%). Most of the patients underwent low anterior resection [23 patients (51.2%)] and abdominoperineal resection [16 patients (35.6%)]. Correlation between clinical and pathologic staging was as expected. Twenty-nine patients (64.4%) of the 45 that were initially included started adjuvant chemotherapy. A statistically significant relationship between pathologic stage (grouped I-II vs. III) and the use of adjuvant chemotherapy was found (p=0.033; chi-square test). Radiotherapy- and chemotherapy-induced toxicity did not differ from that previously reported. With a median follow-up of 65.46 months, a total of 10 recurrences have been diagnosed, all of them in stage III patients. Overall survival rate at five years was 76% for the complete population included. CONCLUSION: Multidisciplinary treatment of resectable rectal cancer in a third-level hospital is feasible. Although efficacy results are comparable to those previously reported in the literature, further improvements in clinical staging as well as in adjuvant chemotherapy indication are desirable (AU)


No disponible


Assuntos
Humanos , Masculino , Feminino , Neoplasias Retais/terapia , Resultado do Tratamento , Oncologia/métodos , Oncologia/estatística & dados numéricos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Reto/patologia , Terapia Combinada/métodos , Terapia Combinada , Estudos Longitudinais , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias
14.
Am J Transplant ; 9(3): 439-51, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19191767

RESUMO

Numerous steatotic livers are discarded as unsuitable for transplantation because of their poor tolerance of ischemia-reperfusion(I/R). The injurious effects of angiotensin (Ang)-II and the benefits of Ang-(1-7) in various pathologies are well documented. We examined the generation of Ang II and Ang-(1-7) in steatotic and nonsteatotic liver grafts from Zucker rats following transplantation. We also studied in both liver grafts the effects of Ang-II receptors antagonists and Ang-(1-7) receptor antagonists on hepatic I/R damage associated with transplantation. Nonsteatotic grafts showed higher Ang II levels than steatotic grafts, whereas steatotic grafts showed higher Ang-(1-7) levels than nonsteatotic grafts. Ang II receptor antagonists protected only nonsteatotic grafts against damage, whereas Ang-(1-7) receptor antagonists were effective only in steatotic grafts. The protection conferred by Ang II receptor antagonists in nonsteatotic grafts was associated with ERK 1/2 overexpression, whereas the beneficial effects of Ang-(1-7) receptor antagonists in steatotic grafts may be mediated by NO inhibition. Our results show that Ang II receptor antagonists are effective only in nonsteatotic liver transplantation and point to a novel therapeutic target in liver transplantation based on Ang-(1-7), which is specific for steatotic liver grafts.


Assuntos
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Fígado Gorduroso/metabolismo , Saúde , Transplante de Fígado , Fragmentos de Peptídeos/metabolismo , Angiotensina I/genética , Angiotensina II/genética , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Apoptose , Fígado Gorduroso/genética , Fígado Gorduroso/patologia , Fígado Gorduroso/cirurgia , Sobrevivência de Enxerto , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fragmentos de Peptídeos/genética , Ratos , Receptores de Angiotensina/metabolismo
17.
Radiat Prot Dosimetry ; 127(1-4): 477-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17627956

RESUMO

Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexaphosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexaphosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo.


Assuntos
Ácido Fítico/administração & dosagem , Lesões por Radiação/metabolismo , Lesões por Radiação/prevenção & controle , Urânio/farmacocinética , Urânio/intoxicação , Animais , Quelantes/administração & dosagem , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Humanos , Taxa de Depuração Metabólica/efeitos dos fármacos , Lesões por Radiação/etiologia , Protetores contra Radiação/administração & dosagem , Ratos , Resultado do Tratamento , Urânio/isolamento & purificação
18.
Radiat Prot Dosimetry ; 127(1-4): 444-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17545661

RESUMO

This paper describes the objectives, and reviews the progress, of the European project 'Treatment Initiatives After Radiological Accidents' (TIARA). TIARA forms part of the 'Preparatory Action for Security Research' (PASR) launched by the European Commission in 2004. The Preparatory Action is intended to reach preliminary conclusions on the needs for the security of EU citizens. It prepared a comprehensive Security Research Programme as part of the Commission's Seventh Framework Programme proposal, which was adopted in 2006 and launched in 2007. The principal purpose of TIARA is to constitute a European network that will participate in facilitating the management of a crisis in the event of the malevolent dispersal of radionuclides into the public environment.


Assuntos
Cuidados Críticos/métodos , Cuidados Críticos/organização & administração , União Europeia/organização & administração , Lesões por Radiação/diagnóstico , Lesões por Radiação/terapia , Protetores contra Radiação/administração & dosagem , Liberação Nociva de Radioativos/prevenção & controle , Humanos
19.
Appl Radiat Isot ; 62(6): 829-46, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15799861

RESUMO

The scientific basis for the treatment of the contamination of the human body by plutonium, americium and other actinides is reviewed. Guidance Notes are presented for the assistance of physicians and others who may be called upon to treat workers or members of the public who may become contaminated internally with inhaled plutonium nitrate, plutonium tributyl phosphate, americium nitrate or americium oxide.


Assuntos
Amerício/intoxicação , Plutônio/intoxicação , Guias de Prática Clínica como Assunto , Humanos , Ácido Pentético/efeitos adversos , Ácido Pentético/farmacocinética , Ácido Pentético/uso terapêutico , Intoxicação/terapia
20.
Eye (Lond) ; 19(12): 1290-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15618975

RESUMO

AIMS: To study the effect of flap thickness on the visual and refractive outcome of myopic laser in situkeratomileusis (LASIK) surgery. METHODS: A total of 196 myopic eyes with spherical equivalent (SE) from -2.00 to -5.00 dioptres which underwent LASIK were studied retrospectively. Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA) and manifest refraction were measured up to 6 months postoperatively. Logistic and linear regression analyses were used to examine the correlation of flap thickness to visual and refractive outcomes, postoperative complications and enhancement rate. RESULTS: UCVA at 1 week and 1 month, but not at 1 day and at 6 months (P>0.05), were negatively correlated to flap thickness (P<0.05). BCVA was unrelated to flap thickness (P>0.05). At 1-month post-LASIK sphere and cylinder were not related to flap thickness (P>0.05), but spherical equivalent was negatively correlated (P<0.05). Significant negative correlations with the sphere and SE were noticed at 6 months for the eyes not requiring enhancements (P<0.05). Flap thickness had no significant relationship to postoperative complications (P>0.05) and no significant predictive value on the rate of enhancement procedures or the efficacy, safety and predictability indices (P>0.05). CONCLUSIONS: In myopic LASIK thinner flaps are associated with faster visual recovery and less myopic SE, but the BCVA and the final UCVA are independent of flap thickness. Postoperative complications are unrelated to flap thickness. Flap thickness does not affect the efficacy, safety and predictability, or the rate of enhancement procedures.


Assuntos
Córnea/patologia , Ceratomileuse Assistida por Excimer Laser In Situ/métodos , Miopia/cirurgia , Retalhos Cirúrgicos/patologia , Adulto , Topografia da Córnea , Métodos Epidemiológicos , Feminino , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Masculino , Pessoa de Meia-Idade , Miopia/fisiopatologia , Seleção de Pacientes , Refração Ocular , Resultado do Tratamento , Acuidade Visual
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