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1.
Rev Esp Geriatr Gerontol ; 57(4): 205-211, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35872030

RESUMO

INTRODUCTION: There are few studies on Fracture Liaison Service (FLS) that evaluate older patients after a hip fracture (HF) through comprehensive geriatric assessment. We aim to determine these patients' characteristics, outcomes, and prescribed treatments. METHODS: A retrospective observational study of a cohort of patients older than 65 years admitted with HFs to an orthogeriatric unit between February 25th (2013) and December 16th (2016). After hospitalization, those patients with a good baseline social, functional, and cognitive situation were referred to the FLS. A comprehensive geriatric assessment and treatment adjustment were conducted. A comparison between FLS patients and HF patients non-referred was made. RESULTS: From 1887 patients admitted to the orthogeriatric unit, 469 (23%) were referred to the FLS. Of those, 335 were women (77.2%) and 337 (77.6%) lived in the community. The FLS patients had a better functional status (97.1% of the patients with independent gait versus 79.2%) than non-FLS patients (p<0.001). After 3 months in the FLS, 356 (82%) patients had independent gait and had improved their analytical values. Antiosteoporotic treatment was prescribed to 322 patients (74%), vitamin D supplements to 397 (91.5%), calcium to 321 (74%), and physical exercise to 421 (97%). CONCLUSIONS: Patients referred to an FLS were younger, with a better functional and cognitive situation. At hospital discharge, they frequently presented gait impairment and laboratory abnormalities (anemia, hypoproteinemia, vitamin D deficiency) that presented good recovery due to the patient's previous baseline. These patients benefit from comprehensive treatment (pharmacological and non-pharmacological).


Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Fraturas do Quadril/etiologia , Humanos , Masculino , Osteoporose/tratamento farmacológico , Vitamina D
2.
J Geriatr Oncol ; 13(6): 813-820, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35311655

RESUMO

OBJECTIVES: To describe a perioperative cross-speciality geriatrics program for patients aged >80 years with colorectal cancer (CRC), aimed to detect and manage frailty and to understand its influence on clinical outcomes. MATERIALS AND METHODS: Patients aged >80 years with CRC and proposed for surgery were included from October 2018 to March 2020. Comprehensive geriatric assessments (CGA) were performed. Patients were classified according to the estimated physiological reserve, from fit, frail patients and even the disabled: CGA-1, CGA-2, CGA-3, and CGA-4. Individualised treatment was adapted to each patient's situation. Patients who underwent surgery were followed up by a geriatrician. The presence of complications, length of stay, hospital readmissions at 30 days, and short- and long-term mortality were recorded. RESULTS: Seventy-four patients were included. The mean age was 84.5 ± 4.5 years. 55.4% patients were classified as CGA-1, 24.3% as CGA-2, 16.2% as CGA-3, and 4.1% as CGA-4. No CGA-4 patient was operated on. Frail (CGA-2 and CGA-3) patients had higher medical complications (50% vs 21.2%, p < 0.05) and delirium (30% vs 9.1%, p < 0.05) than fit patients (CGA-1). They also had higher rates of surgical complications (20% vs 15.2%), longer hospital stay (10 ± 6.2 vs 8.4 ± 4.2 days), 30-day readmissions (15% vs 6.3%), and mortality at six (10% vs 3%) and twelve months (20% vs 6.1%), although it was not statistically significant. CONCLUSION: CGA and prehabilitation can classify patients according to their frailty status, support clinicians in decision-making to achieve tailored treatment, and detect clinical conditions for intervention in multiple domains of health in the perioperative period.


Assuntos
Neoplasias Colorretais , Fragilidade , Assistência Perioperatória , Exercício Pré-Operatório , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/cirurgia , Fragilidade/complicações , Avaliação Geriátrica/métodos , Humanos
3.
Braz J Phys Ther ; 24(6): 479-487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31378633

RESUMO

OBJECTIVE: To study the adherence of an Early Inpatient Exercise Program in patients with acute hip fracture, identify variables associated with its performance, and its association to one-year survival. METHODS: Observational longitudinal study of a cohort of 509 patients, admitted consecutively with a hip fracture in La Paz University Hospital (Madrid, Spain). Data included sociodemographic variables, pre-fracture physical functioning, cognitive impairment, comorbidities, measure of exercise adherence (pre-surgery exercise, post-surgery exercise, and rehabilitation sessions) and vital status at follow-up. One year after the fracture, either patients or relatives were contacted by telephone to ascertain their vital status. Data were analyzed using logistic regressions and multivariate Cox proportional hazards regression. RESULTS: Three quarters of patients (76.0%) were able to comply with the Early Inpatient Exercise Program. Factors associated with adherence were: living at home (Odds Ratio (OR)=3.39; 95% Confidence Interval (CI): 2.03, 5.64), absence of pre-fracture disability (OR=3.78; 95% CI: 2.21, 6.47), absence of pre-fracture cognitive impairment (OR=2.36; 95% CI: 1.36, 4.07) and comorbidities (OR=1.66; 95% CI: 1.03, 2.67). Early Inpatient Exercise Program adherence was associated with one-year survival (HR=1.62; 95% CI: 1.06, 2.49). CONCLUSIONS: The adherence with an Early Inpatient Exercise Program is high and is associated with 1-year survival. It is important to make a stronger effort to encourage participation in Early Inpatient Exercise Program in the 24% currently non-compliant, and in those with cognitive and physical impairments.


Assuntos
Disfunção Cognitiva/fisiopatologia , Fraturas do Quadril/reabilitação , Atividades Cotidianas , Exercício Físico , Terapia por Exercício , Fraturas do Quadril/mortalidade , Hospitalização , Humanos , Pacientes Internados , Estudos Longitudinais , Espanha
4.
Rev Esp Geriatr Gerontol ; 53(2): 81-84, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-28784246

RESUMO

INTRODUCTION: The prevalence of pelvic fracture (PF) due to frailty is increasing, leading to an increase in functional impairment in the patient, as well as increasing morbidity and mortality. The aim of the present study is to gain knowledge about the sociodemographic characteristics, as well as the functional features, of patients admitted to hospital with PF and evaluated by a Geriatrics department. The functional burden of PF and the potential influence of geriatric interventions are also assessed. MATERIAL AND METHODS: A retrospective study conducted between 1995 and 2015 on all patients older than 65 years old with PF admitted to the Traumatology department, and then assessed in the Geriatrics Department. Sociodemographic information was also collected (age, gender and place of residence), as well as data from the geriatric assessment (baseline situation and at hospital admission), hospital stay, within hospital mortality, and discharge. RESULTS: The study included 271 patients with a mean age of 81.1±7 years, and mainly women (81.2%). The median hospital stay was 9 days (interquartile range 5 to 14 days). The ability to walk independently decreased after PF from 72.3% to 3.6%. Severe disability cases increased in activities of daily living from 7.9% to 79.5%. Within hospital mortality was 2.2%. As regards medical follow-up consultations, the mean length of stay was significantly reduced compared to the assessment consultations (10.0±7.8 vs 16.1±12.0 days, P<.001) CONCLUSION: PF patients evaluated by the Geriatrics Department were mainly women, with advanced age, and a severe functional impairment secondary to PF. The intervention of a geriatrician could contribute to optimise hospital resources.


Assuntos
Fraturas Ósseas/complicações , Fraturas Ósseas/fisiopatologia , Fragilidade/complicações , Fragilidade/fisiopatologia , Ossos Pélvicos/lesões , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Encaminhamento e Consulta , Estudos Retrospectivos
5.
Knee Surg Sports Traumatol Arthrosc ; 25(11): 3508-3514, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27522590

RESUMO

PURPOSE: To determine whether the design of the femoral component influenced patient outcomes. METHODS: Two hundred and thirty-seven patients were randomized to compare functional outcomes between single-radius TKA (SR, 118 patients) and multi-radius TKA (MR, 119 patients) with a minimum follow-up of 5 years. Prospective pre- and postoperative assessments were performed by the clinical and radiological criteria of the Knee Society Score (KSS), WOMAC and Short-Form 12 (SF12) questionnaires. The extension mechanism was assessed based on the quadriceps strength and chair test. Patient satisfaction was also assessed. RESULTS: The median follow-up was 5.7 (range 5-7) years. At last follow-up, significant better KSSs (p = 0.001), range of motion (p = 0.001), extension lag (p = 0.020), quadriceps strength (p = 0.004), chair test (p = 0.032) and WOMAC pain (p = 0.002) were found in the SR group. Moreover, the improvements of these variables were early in the SR group (from 6 postoperative months). There were no significant differences in WOMAC function or SF12 physical and mental components. The revision rate and implant survival were similar in both groups. Satisfaction rate was significantly higher in SR group (p = 0.032). CONCLUSION: This study shows better results with SR cruciate-retaining femoral component than MR component. The use of SR system is recommended because, although the clinically relevant differences were moderate, the functional improvement was earlier and the patient satisfaction higher with this design. LEVEL OF EVIDENCE: Therapeutic study, Level I.


Assuntos
Artroplastia do Joelho/métodos , Fêmur/cirurgia , Articulação do Joelho/cirurgia , Prótese do Joelho , Desenho de Prótese , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Prospectivos , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Método Simples-Cego , Resultado do Tratamento
6.
Injury ; 47(7): 1530-5, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27168082

RESUMO

PURPOSE: To analyze prospectively the influence of the timing of surgery on morbidity and mortality, and to assess whether the early surgery within 2 days admission may be a reliably healthcare quality indicator. METHODS: Prospective observational study of 628 patients age 60 or older who had been co-managed between surgeons and internists. Based on the literature, many potential factors influencing outcomes were collected to control confounding regard to surgery delay, complications and mortality. Multivariate logistic regression and Cox regression models were used to assess effects on the delay and mortality, respectively. RESULTS: Mean Charlson index was 2.3, and 284 patients had at least 3 comorbidities. Mean timing of surgery was 3.6 days (range 0-20). 418 patients were fit for surgery, of which 180 underwent surgery within 2 days. Delay for surgery more than 2 days was significantly associated with ASA >2, Charlson >2 and anticoagulant therapy. Medical complications were not significantly associated with delayed surgery more than 2 days. Mortality rate was 0.9% in-hospital, 3.4 at 1 month, 7.0% at 3 months, and 13.6% at 12 months. There were no significant differences in in-hospital, 3-month or 1-year mortality between patients operated within 2 days and those operated at 3-4 days, but delayed more than 4 days was associated with higher 1-year mortality. Likewise, patients readmitted within 30 days had higher in-hospital mortality. Excluding unfit for surgery patients at admission, there was no significant difference in 3-month or 1-year mortality between patients operated within 2 days and those with delayed surgery. CONCLUSIONS: Delaying surgery up to 4 days was not associated with higher morbidity or mortality rates. We recommend concentrating more on preoperative optimizing the condition of patient with sufficient medical treatment rather than being bound by a universal timing of surgery.


Assuntos
Artroplastia de Quadril , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/cirurgia , Tempo para o Tratamento/estatística & dados numéricos , Idoso de 80 Anos ou mais , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/mortalidade , Comorbidade , Feminino , Fraturas do Quadril/mortalidade , Fraturas do Quadril/fisiopatologia , Mortalidade Hospitalar/tendências , Humanos , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Indicadores de Qualidade em Assistência à Saúde , Índice de Gravidade de Doença , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento
7.
J Arthroplasty ; 31(10): 2152-5, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27129761

RESUMO

BACKGROUND: The purpose of this study was to compare outcomes and complications after total knee arthroplasty (TKA) between end-stage renal disease (ESRD) patients and patients without renal insufficiency. METHODS: A retrospective case-control study with prospectively collected data was carried out to compare 15 ESRD patients with a matched cohort of 30 nonrenal patients. Clinical evaluation was performed by the Knee Society Scores (KSS) and reduced Western Ontario MacMasters University (WOMAC) questionnaire. Radiologic evaluation was also performed. RESULTS: The mean postoperative follow-up was 3.4 years (range, 2-6). In the ESRD, the mean hospital stay and transfusion rate were significantly higher than control group. Preoperatively and postoperatively, there were no significant differences in KSS-knee or WOMAC-pain scores, but KSS-function and WOMAC-function were significantly lower in the ESRD group. There was no significant difference between groups in mean gain of KSS-function (45.1 vs 43.2, P = .071), but there was a significant lower mean gain for WOMAC-function in the ESRD group (37.0 vs 44.0, P = .003). In the ESRD group, 3 patients presented medical complications which were treated successfully. There were 2 superficial infections and no deep infection. One patient died at 30 postoperative months. In the control group, there were no medical complications, infections, or deaths during the follow-up period. In ESRD group, there were 2 knees with radiolucent lines. In either group, there was no loosening or revision. CONCLUSION: TKA was a successful procedure for knee osteoarthritis in most ESRD patients. Dialysis patients may expect improvement in function after TKA, but the patients need to be informed of the possible risk of postoperative severe medical complications due to nature of their renal disease.


Assuntos
Artroplastia do Joelho/efeitos adversos , Falência Renal Crônica/complicações , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/etiologia , Idoso , Estudos de Casos e Controles , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Período Pós-Operatório , Insuficiência Renal Crônica , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
8.
Eur Spine J ; 25(6): 1806-12, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27048540

RESUMO

PURPOSE: To compare outcomes between transdiscal and conventional pedicle fixation for high-grade L5-S1 spondylolisthesis. METHODS: This was a retrospective case-control study with patients prospectively followed. Twenty-five consecutive patients with mean age of 36.7 years underwent transdiscal fixation, and 31 other with mean age of 42.0 years to pedicle fixation were clinically and radiographically compared. Clinical assessments were performed using Oswestry Disability Index (ODI), Core Outcomes Measures Index (COMI), Short-Form 12 (SF-12), and pain visual analog scale (VAS). Radiographic spinopelvic parameters were also evaluated. The mean follow-up was 2.7 years (range 2.0-5.3). RESULTS: Preoperative data were comparable between groups. Surgery time, blood loss, and hospital stay were similar between groups. At last follow-up, clinical and radiographic outcomes were significantly improved in both groups. Postoperatively, both lumbar and leg pain VAS were similar between groups, but ODI (20.2 vs. 31.6, p = 0.010), COMI (1.6 vs. 2.8, p = 0.012), and SF-12 physical (84.3 vs. 61.5, p = 0.004) and mental (81.5 vs. 69.4, p = 0.021) scores were significantly better in the transdiscal group. The neurologic complication rate was similar in both groups. There were 4 pseudoarthroses in the pedicle group, and none in the transdiscal group. CONCLUSION: L5-S1 transdiscal screw fixation provided better functional and radiographic outcomes at medium-term than conventional pedicle fixation for high-grade spondylolisthesis, although transdiscal sacral screws are difficult to place in correct position.


Assuntos
Vértebras Lombares/cirurgia , Parafusos Pediculares , Sacro/cirurgia , Fusão Vertebral , Espondilolistese/cirurgia , Adulto , Dor nas Costas , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/métodos , Fusão Vertebral/estatística & dados numéricos , Resultado do Tratamento
9.
J Arthroplasty ; 30(8): 1328-32, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25795233

RESUMO

A prospective matched cohort study was performed to compare outcomes of total knee arthroplasties (TKA) between 29 patients with posttraumatic osteoarthritis (POA) after a fracture of tibial plateau and 58 patients underwent routine TKA. Mean follow-up was 6.7 years. There were no significant differences in KSS, WOMAC, SF12 scores or range of motion. In the control group there were no complications. In the posttraumatic group, complications occurred in 4 patients (13.7%) (P=0.010) including partial patellar tendon detachment, superficial infection, skin necrosis, and knee stiffness. Only this last patient required revision for manipulation under anesthesia. Also, there was a revision for tibial aseptic loosening in each group. TKA is an effective treatment for POA after tibial plateau fracture. We recommend the prior removal of hardware, as well as tibial tubercle osteotomy when necessary.


Assuntos
Artroplastia do Joelho , Traumatismos do Joelho/complicações , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Fraturas da Tíbia/complicações , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Fraturas Intra-Articulares/complicações , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/etiologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Resultado do Tratamento
10.
J Arthroplasty ; 29(6): 1192-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24355257

RESUMO

A prospective matched cohort study was performed to compare outcomes of cementless total knee arthroplasties between 171 knees in obese patients (BMI ≥ 30) and 171 non-obese patients (BMI < 30). Mean follow-up was 7 years. There were no significant differences in overall functional outcomes or components alignment. In the obese group, there were 14 perioperative complications, 9 revisions, and 5 other patients were considered clinical failures, whereas in the non-obese group there were 3, 5, and 7, respectively. There were no significant differences between obese class I-II and class III (morbid) subgroups. The obese and non-obese groups had similar implant survivorship at 7 years. Although TKA outcome in obese was satisfactory, these patients should be informed of the perioperative risks, and advised to lose weight prior to surgery.


Assuntos
Artroplastia do Joelho/métodos , Obesidade/complicações , Osteoartrite do Joelho/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cimentação , Estudos de Coortes , Feminino , Seguimentos , Humanos , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Estudos Prospectivos , Resultado do Tratamento
11.
Endocrinology ; 151(7): 3061-73, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20444946

RESUMO

Elevated glucose and saturated fatty acids synergize in inducing apoptosis in INS832/13 cells and in human islet cells. In order to gain insight into the molecular mechanism(s) of glucolipotoxicity (Gltox), gene profiling and metabolic analyses were performed in INS832/13 cells cultured at 5 or 20 mm glucose in the absence or presence of palmitate. Expression changes were observed for transcripts involved in mitochondrial, lipid, and glucose metabolism. At 24 h after Gltox, increased expression of lipid partitioning genes suggested a promotion of fatty acid esterification and reduced lipid oxidation/detoxification, whereas changes in the expression of energy metabolism genes suggested mitochondrial dysfunction. These changes were associated with decreased glucose-induced insulin secretion, total insulin content, ATP levels, AMP-kinase activity, mitochondrial membrane potential and fat oxidation, unchanged de novo fatty acid synthesis, and increased reactive oxygen species, cholesterol, ceramide, and triglyceride levels. However, the synergy between elevated glucose and palmitate to cause ss-cell toxicity in term of apoptosis and reduced glucose-induced insulin secretion only correlated with triglyceride and ceramide depositions. Overexpression of endoplasmic reticulum glycerol-3-phosphate acyl transferase to enhance lipid esterification amplified Gltox at intermediate glucose (11 mm), whereas reducing acetyl-coenzyme A carboxylase 1 expression by small interfering RNA to shift lipid partitioning to fat oxidation reduced Gltox. The results suggest that Gltox entails alterations in lipid partitioning, sterol and ceramide accumulation, mitochondrial dysfunction, and reactive oxygen species production, all contributing to altering ss-cell function. The data also suggest that the early promotion of lipid esterification processes is instrumental in the Gltox process.


Assuntos
Ceramidas/metabolismo , Colesterol/metabolismo , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Acetiltransferases/genética , Acetiltransferases/fisiologia , Animais , Apoptose/efeitos dos fármacos , Glucose/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Modelos Biológicos , Nucleotidiltransferases/genética , Nucleotidiltransferases/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Palmitatos/farmacologia , Interferência de RNA , Ratos
12.
Free Radic Res ; 41(8): 874-83, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17654044

RESUMO

We studied the effects of intense exercise on the neutrophil antioxidant enzyme activities and gene expression. Blood samples were taken from seven cyclists in basal conditions and 3 h after two competition stages of 165 km. Serum creatine kinase (CK) activity, plasma carbonyl derivatives and uric acid levels increased after exercise. The cycling stage induced neutrophilia and increased myeloperoxidase (MPO) activity and reactive oxygen species (ROS) production. Antioxidant enzyme activities (catalase, glutathione peroxidase and superoxide dismutase) decreased after exercise, although gene expression increased. Immunocytochemistry showed catalase (CAT) enzyme equally distributed between the cytoplasm and organelles before exercise, and after exercise the cytoplasmic CAT levels were reduced and were absent in the compartments. After in vitro stimulation with opsonized zymosan (OZ) the extracellular CAT levels increased. This suggests a CAT secretion in order to avoid neutrophil-induced oxidative damage at a local level or to regulate the function of ROS as extracellular signalling molecules.


Assuntos
Antioxidantes/metabolismo , Catalase/genética , Exercício Físico , Expressão Gênica , Neutrófilos/enzimologia , Peroxidase/genética , Explosão Respiratória/genética , Adulto , Catalase/análise , Catalase/metabolismo , Citoplasma/enzimologia , Humanos , Imuno-Histoquímica , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/ultraestrutura , Peroxidase/análise , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Zimosan/farmacologia
13.
Eur J Appl Physiol ; 98(3): 263-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16896722

RESUMO

The response of lymphocyte and plasma antioxidant defences to a prolonged exercise as a cycling stage in a professional race was analysed. Antioxidant enzyme activities and gene expression, carbonyl derivative and MDA levels were determined in lymphocytes. Plasma levels of vitamin E, carotenes, protein carbonyl derivatives and the test d-Roms were measured. Significant increases in plasmatic carbonyls and in the test d-Roms were observed after the cycling stage. No significant differences were found in the lymphocyte MDA and carbonyl derivative levels. A significant increase was found in plasma vitamin E concentration after the cycling stage; however, the lymphocyte vitamin E concentration did not change. Significant increases were observed in lymphocyte total superoxide dismutase (SOD) activity and in the levels of CuZn-SOD and Mn-SOD isoenzymes. The moderate levels of oxidative stress in the lymphocyte induced a cellular adaptation to exercise enough to counteract the negative effects of oxidative stress.


Assuntos
Antioxidantes/análise , Exercício Físico , Linfócitos/enzimologia , Estresse Oxidativo , Soro/química , Biomarcadores/análise , Carotenoides/sangue , Catalase/sangue , Glutationa Peroxidase/sangue , Humanos , Masculino , Superóxido Dismutase/sangue , Vitamina E/sangue
14.
Endocrinology ; 144(1): 335-45, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12488362

RESUMO

The potential toxic effects of high extracellular concentrations of fatty acids were tested in beta(INS-1)-cells cultured in the absence of serum, a condition known to alter cell survival in various systems. This may in part mimic the situation in type 1 or 2 diabetes where beta-cells are already insulted by various stressful conditions, such as cytokines and oxidative stress. Serum removal caused, over a 36-h period, oxidative stress and an early impairment of mitochondrial function, as revealed by increased superoxide production and markedly reduced mitochondrial membrane potential, but a lack of cytochrome c and apoptosis-inducing factor release in the cytosol. The fatty acids palmitate and oleate considerably accelerated the apoptosis process in serum-starved cells, as revealed by fluorescence-activated cell sorting analysis, morphological changes, chromatin condensation, DNA laddering, poly(ADP-ribose) polymerase cleavage, cytochrome c and apoptosis-inducing factor release, and increased levels of Bax and cytosolic caspase-2. The fatty acids also increased nitric oxide production, apparently independently of inducible nitric oxide synthase induction. Under the same experimental conditions, elevated glucose alone had only a marginal effect on beta-cell apoptosis. Together the results indicate that elevated concentrations of fatty acids are particularly efficient in accelerating the rate of apoptosis of already stressed beta(INS-1)-cells displaying altered mitochondrial function, and that the mitochondrial arm of the apoptosis process is involved in beta-cell lipotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Sangue , Meios de Cultura Livres de Soro , Ácidos Graxos/farmacologia , Ilhotas Pancreáticas/ultraestrutura , Mitocôndrias/fisiologia , Proteínas Proto-Oncogênicas c-bcl-2 , Fator de Indução de Apoptose , Caspase 2 , Caspases/metabolismo , Linhagem Celular , Sobrevivência Celular , Cromatina/ultraestrutura , Grupo dos Citocromos c/metabolismo , Citosol/metabolismo , Fragmentação do DNA , Flavoproteínas/metabolismo , Citometria de Fluxo , Glucose/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Potenciais da Membrana , Proteínas de Membrana/metabolismo , Mitocôndrias/ultraestrutura , Óxido Nítrico/metabolismo , Ácido Oleico/farmacologia , Estresse Oxidativo , Ácido Palmítico/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Superóxidos/metabolismo , Proteína X Associada a bcl-2
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