RESUMO
BACKGROUND: Climbing via ferrata routes is becoming more and more popular. The growing number of via ferrata climbers is associated with an increasing number of accidents. In addition to adequate equipment and its correct handling, knowledge of specific risks and safety-related behaviour play an important role for safety on via ferrata routes. The goal of this study was to collect data on equipment, via ferrata-specific risk knowledge, safety-related behaviour, and general risk-taking behaviour of via ferrata climbers. METHODS: In this survey, data of 332 climbers of different via ferrata routes in Tyrol (Austria) were collected using a standardised data entry form including socio-demographic data, the use of via ferrata-specific equipment and first aid equipment. Knowledge of via ferrata-specific risks was assayed by a questionnaire including 4 questions. Additionally, safety-related behaviour and general risk-taking behaviour of the via ferrata climbers were evaluated. RESULTS: 92â% of the interviewed persons were wearing a helmet and helmet use was significantly lower in females (86â%) compared to males (96â%). In total, 10â% of the via ferrata climbers used inadequate belaying equipment or no equipment at all. The 4 questions related to via ferrata-specific risks were correctly answered by an average of 46â% of the climbers. A partner check was carried out by 76â% before starting the tour. 96â% of the climbers stated they ask the climber ahead of them for the possibility to overtake and wait for a suitable and safe spot. 64â% reported that they would not pass without self-belay. General risk-taking behaviour was scored at 4.26â±â1.75 with significant differences between female and male via ferrata climbers (3.79â±â1.37 vs. 4.53â±â1.88). CONCLUSION: Although most of the via ferrata climbers use adequate equipment, helmet use could be optimised in females. Via ferrata climbers should be better informed of the risks of climbing via ferrata routes and safety-related behaviour. Preventive measures including information panels at the entrances of the via ferrata routes and broad information campaigns could contribute to reduce the number of accidents.
Assuntos
Traumatismos em Atletas/prevenção & controle , Montanhismo/estatística & dados numéricos , Equipamento de Proteção Individual/estatística & dados numéricos , Equipamentos de Proteção/estatística & dados numéricos , Gestão da Segurança/estatística & dados numéricos , Equipamentos Esportivos/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Traumatismos em Atletas/epidemiologia , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Montanhismo/lesões , Medição de Risco/métodos , Assunção de Riscos , Distribuição por Sexo , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Hiking is one of the most popular activities among the elderly in Alpine regions. Due to the long-lasting, moderately intensive nature of this form of physical activity, hiking is generally considered to be beneficial to health. However, it is currently unclear whether once-weekly hiking--as commonly practiced at weekends--really does yield such positive effects in elderly persons aged 60 years and over. OBJECTIVES: This study investigated the effect of a single weekly mountain hiking session on cardiovascular risk factors. MATERIALS AND METHODS: A 9-month mountain hiking program was completed by 14 male (age 65.6 ± 2.7 years) and 10 female (age 66.2 ± 4.4 years) elderly participants. The program consisted of a single weekly hiking session with the goal of achieving a 500-m altitude increase within 3 h. Before and after the 9-month program, an electrocardiogram (ECG) was performed and blood pressure, glycated hemoglobin (HbA1c), high-density (HDL) and low-density lipoprotein (LDL) measurements were made. RESULTS: The elderly participants showed a normal cardiovascular risk profile at the start of the investigation. The estimated net energy expenditure for one hiking session was approximately 521 ± 91 kcal. Over the 9-month period, no changes were found in any of the investigated parameters for the entire group. However, participants with untreated hypertension showed a reduced systolic blood pressure. CONCLUSION: The present investigation showed that moderate-intensity activity only at weekends does not improve cardiovascular risk factors in elderly persons with a relatively normal cardiovascular risk profile. Conversely, elderly persons suffering from hypertension might profit from such a practice.
Assuntos
Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/fisiopatologia , Frequência Cardíaca/fisiologia , Aptidão Física/fisiologia , Caminhada/fisiologia , Idoso , Altitude , Doenças Cardiovasculares/diagnóstico , Terapia por Exercício , Feminino , Avaliação Geriátrica , Humanos , Masculino , Condicionamento Físico Humano/métodos , Fatores de Risco , Resultado do TratamentoRESUMO
Reactive oxygen species are thought to partly be responsible for the hypoxia induced performance decrease. The present study evaluated the effects of a broad based antioxidant supplementation or the combined intake of alpha-ketoglutaric acid (α-KG) and 5-hydroxymethylfurfural (5-HMF) on the performance decrease at altitude. 18 healthy, well-trained males (age: 25±3 years; height: 179±6 cm; weight: 76.4±6.8 kg) were randomly assigned in a double-blind fashion to a placebo group (PL), a α-KG and 5-HMF supplementation group (AO1) or a broad based antioxidant supplementation group (AO2). Participants performed 2 incremental exercise tests to exhaustion on a cycle ergometer; the first test under normoxia and the second under hypoxia conditions (simulated altitude, FiO2=13% ~ 4 300 m). Supplementation started 48 h before the hypoxia test. Maximal oxygen uptake, maximal power output, power output at the ventilatory and lactate threshold and the tissue oxygenation index (NIRS) were measured under both conditions. Oxidative stress markers were measured before the supplementation and after the hypoxia test. Under hypoxia conditions all performance parameters decreased in the range of 19-39% with no differences between groups. A significant change from normoxia to hypoxia (p<0.001) and between groups (p=0.038) were found for the tissue oxygenation index. Post hoc test revealed significant differences between the PL and both, the AO1 and the AO2 group. The oxidative stress parameter carbonyl protein changed from normoxia to hypoxia in all participants and 4-hydroxynonenal decreased in the AO1 group only. In conclusion the results suggest that short-term supplementation with an antioxidant does not prevent the performance decrease at altitude. However, positive effects on muscle oxygen extraction, as indicated by the tissue oxygenation index, might indicate that mitochondrial functioning was actually influenced by the supplementation.
Assuntos
Antioxidantes/farmacologia , Furaldeído/análogos & derivados , Ácidos Cetoglutáricos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Adulto , Aldeídos/metabolismo , Altitude , Antioxidantes/administração & dosagem , Desempenho Atlético/fisiologia , Método Duplo-Cego , Exercício Físico/fisiologia , Teste de Esforço , Furaldeído/administração & dosagem , Furaldeído/farmacologia , Humanos , Hipóxia/fisiopatologia , Ácidos Cetoglutáricos/administração & dosagem , Ácido Láctico/sangue , Masculino , Consumo de Oxigênio , Adulto JovemRESUMO
Intermittent hypoxia (IH) is a promising approach to induce acclimatization and hence lower the risk of developing acute mountain sickness (AMS). We hypothesized that a short-term IH protocol in normobaric hypoxia (7 × 1 h to 4500 m) effectively increases the hypoxic ventilatory response (HVR) and reduces the incidence and severity of AMS. Therefore, 26 men (25.5 ± 4.4 years), assigned in a double-blinded fashion to the hypoxia group (HG) or placebo group (PG), spent 8 h at 5300 m before (PRE) and 2 days after cessation of the IH protocol (POST). Measurements included the evaluation of the Lake Louise Score (LLS) and the HVR. The severity of AMS decreased from PRE to POST in the HG (from 6.0 ± 2.7 at PRE to 4.1 ± 2.1 at POST), whereas the LLS in the PG stayed high (from 5.7 ± 2.9 to 5.5 ± 2.8, respectively). The HVR in the HG increased from 0.73 ± 0.4 L/min/% at PRE to 1.10 ± 0.5 L/min/% at POST and did not increase in the PG. The reduction of the LLS was inversely related to the changes in the HVR (r = -0.434), but the AMS incidence was not different between the HG and the PG at POST. In conclusion, short-term IH reduced the severity of AMS development during a subsequent 8-h exposure to normobaric hypoxia.
Assuntos
Aclimatação , Doença da Altitude/prevenção & controle , Hipóxia , Montanhismo , Doença Aguda , Adulto , Doença da Altitude/patologia , Análise de Variância , Método Duplo-Cego , Humanos , Masculino , Índice de Gravidade de Doença , Fatores de Tempo , Adulto JovemRESUMO
AIM: To study the effects of a supervised exercise program on serum gamma-glutamyl transferase (GGT), glycemic control and cardiovascular risk factors in pre-diabetic patients with isolated impaired fasting glucose (IFG) and those with IFG plus impaired glucose tolerance (IGT). METHODS: Out of 60 pre-diabetic patients (30 with isolated IFG and 30 with IFG + IGT) 24 were randomly assigned to the supervised exercise program (1 h twice a week) and 36 only obtained counselling on the risk of diabetes and its prevention. Patients have been followed over a 12-month period. RESULTS: The main findings were that patients with IFG + IGT had increased GGT levels at baseline (49.2±27.4 U/L) compared to subjects with isolated IFG (28.1±21.9 U/L) (p<0.01), and that GGT levels improved only after the supervised exercise intervention within the IFG + IGT subjects ( - 17.7±19.6 U/L). Similarly, baseline triglyceride levels were also higher in IFG + IGT patients (p<0.001) and there was a decrease through exercise intervention in these patients only (p<0.05). CONCLUSION: GGT is an unspecific marker of oxidative stress and both high plasma glucose and triglycerides levels may produce oxidative stress. Thus, patients with IFG + IGT seem to have higher levels of oxidative stress than those with isolated IFG. Based on the known association between GGT levels and cardiovascular risk factors, IFG + IGT patients may be at higher risk for the development of cardiovascular diseases. The specific effect of regular exercise on GGT in pre-diabetic patients may contribute to the understanding of the preventive effects related to exercise.
Assuntos
Exercício Físico , Intolerância à Glucose/prevenção & controle , Hiperglicemia/prevenção & controle , Estresse Oxidativo , Estado Pré-Diabético/terapia , gama-Glutamiltransferase/sangue , Adulto , Idoso , Áustria/epidemiologia , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Feminino , Intolerância à Glucose/etiologia , Humanos , Hiperglicemia/etiologia , Hipertrigliceridemia/etiologia , Hipertrigliceridemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/fisiopatologia , Treinamento Resistido , Fatores de RiscoRESUMO
AIM: Soccer is characterized by high injury rates that necessitate interventions for its reduction. The "11" is a multi-modal preventive program that was developed to reduce injury rate. However, outcomes on the effectiveness of the program are not unambiguous and data for the largest group at risk (i.e., male adult amateur players) are missing. The study aims to assess the injury rate in male adult amateur soccer players of different levels and to evaluate the effectiveness of the prevention program the "11". METHODS: Three amateur soccer teams participated in the study during the first round of a competition season. Two teams played at a regional level (6th Italian league) and one team at a provincial level (7th Italian league). The regional league is of a higher skill level compared to the provincial league. Duration and frequency of training and match sessions and the occurrence of time-loss injuries were recorded. One team of the 6th league performed an injury prevention program. RESULTS: The total injury rate for the intervention and the control team in the 6th league was 3.3 (CI 0.7-5.9) and 4.3 (CI 1.3-7.3) injuries/1000 h, respectively (P=0.841). The 6th league control team tended to have a lesser injury rate compared to the 7th league team (P=0.081). The relative risk was 2 fold higher in the 7th compared to the 6th league team (P=0.0285 one tailed). CONCLUSION: Present results show that injury rate in amateur soccer depended rather on the skill level than the prevention program. In this study the prevention program the "11" was not shown to be highly effective in soccer player of intermediate level (i.e., 6th Italian league).
Assuntos
Traumatismos em Atletas/prevenção & controle , Desempenho Atlético/fisiologia , Futebol/lesões , Adulto , Traumatismos em Atletas/epidemiologia , Estudos de Casos e Controles , Humanos , Itália , Masculino , Educação Física e Treinamento/métodos , Adulto JovemRESUMO
Alterations in the autonomic nervous system after ascent to high altitude may be related to the development of acute mountain sickness (AMS). So far, the time course of cardiac autonomic modulation in relation to AMS development during the early hours at altitude is not well established. As AMS develops sometimes as early as 1 h and typically within 6 to 10 h at altitude, evaluating this time period provides information on cardiac autonomic responses with regard to AMS development. Prior studies exclusively investigated autonomic modulations in hypobaric hypoxia. Because barometric pressure per se might influence autonomic nervous system activity, the evaluation of cardiac autonomic alterations caused by hypoxia alone might give new insights on the role of the autonomic nervous system in AMS development. To assess the early responses of acute hypoxia on cardiac autonomic modulation and its association to the development of AMS, 48 male subjects were exposed for 8 h to acute normobaric hypoxia (FiO2 11.0%, 5 500 m respectively). Heart rate variability (HRV) was determined by 5-min recordings of successive NN-intervals in normoxia and after 2, 4, 6 and 8 h in hypoxia. Compared with normoxia, acute exposure to hypoxia decreased total power (TP), high frequency (HF) and low frequency (LF) components as well as the standard deviation of all NN intervals (SDNN), the root mean square of differences of successive NN intervals (rMSSD) and the proportion of differences between adjacent NN intervals of more than 50 ms (pNN50). LF:HF ratio, heart rate (HR) and blood lactate (LA) were augmented, indicating an increase in cardiac sympathetic activity. No differences were found between those who developed AMS and those who did not. Our results confirm reduced HRV with a shift towards sympathetic predominance during acute exposure to hypoxia. However, changes in cardiac autonomic modulations are not related to AMS development in acute normobaric hypoxia.
Assuntos
Doença da Altitude/fisiopatologia , Sistema Nervoso Autônomo/fisiologia , Frequência Cardíaca/fisiologia , Hipóxia/fisiopatologia , Adulto , Humanos , Ácido Láctico/sangue , Masculino , Fatores de Tempo , Adulto JovemRESUMO
AIM: Body composition is highly modifiable through exercise and may be changed by the physical stress of soccer training and competition. Especially body water as a constituent of body composition is assumed to be subjected to changes. It is speculated that during the most important soccer championship the combination of heat and the strenuous competitive program could lead to the development of a chronic state of hypohydration. However, no one tested this hypothesis. Therefore, the purpose of present work was to investigate the impact of the European Soccer Championship 2008 on players' body composition. METHODS: Participants were 14 players of one team, split into Starters (N.=7) and Non-Starters (N.=7). Starters participated in the games, while Non-Starters served as substitutes, with marginal playing times. Body composition was examined by bioelectrical impedance analysis before the championship and 36 hours after the first and second game. RESULTS: After the first game, Starters and Non-Starters showed decreased extra-cellular mass (-3.3% and -5.5%) and body cell mass (-4.1% and -6.1%) compared to prechampionship measurements. The impedance vector graph showed a significant lengthening in both groups (Starters T²=30.5, P=0.000; Non Starters T²=39.0, P=0.000). After the second game, extra-cellular mass (-3.4%) and body weight (-1.1%) decreased in Starters only. ANOVA revealed a significant difference in extra-cellular mass between Starters and Non-Starters (P=0.027). The impedance vector graph was lengthened in the Starters only (T²=17.5, P=0.000). The distance covered during the games was correlated to the percent drop in extra-cellular mass between the end of games 1 and 2 (r=-0.602; P=0.023). CONCLUSION: Players competing in the European championship games experienced a decrease in extra-cellular mass and body weight. The impedance vector graph showed a lengthening, indicating fluid loss. Therefore, proper hydration of players requires diligent attention.
Assuntos
Composição Corporal/fisiologia , Impedância Elétrica , Futebol/fisiologia , Água/metabolismo , Adulto , Análise de Variância , Peso Corporal , Humanos , Adulto JovemRESUMO
We investigated the effects of two 5-wk periods of intermittent hypoxia on running economy (RE). 11 male and female middle-distance runners were randomly assigned to the intermittent hypoxia group (IHG) or to the control group (CG). All athletes trained for a 13-wk period starting at pre-season until the competition season. The IHG spent additionally 2 h at rest on 3 days/wk for the first and the last 5 weeks in normobaric hypoxia (15-11% FiO2). RE, haematological parameters and body composition were determined at low altitude (600 m) at baseline, after the 5 (th), the 8 (th) and the 13 (th) week of training. RE, determined by the relative oxygen consumption during submaximal running, (-2.3+/-1.2 vs. -0.3+/-0.7 ml/min/kg, P<0.05) and total running time (+1.0+/-0.9 vs. +0.4+/-0.5 min, P<0.05) changed significantly between the IHG and CG only during the first 5-wk period. Haematological and cardiorespiratory changes indicate that the improved RE was associated with decreased cardiorespiratory costs and greater reliance on carbohydrate. Intermittent hypoxia did not affect RE during the second 5-wk period. These findings suggest that the effects of intermittent hypoxia on RE strongly depend on the training phase.
Assuntos
Hipóxia/metabolismo , Consumo de Oxigênio/fisiologia , Corrida/fisiologia , Adolescente , Adulto , Altitude , Atletas , Desempenho Atlético/fisiologia , Metabolismo dos Carboidratos/fisiologia , Feminino , Humanos , Masculino , Fatores de Tempo , Adulto JovemRESUMO
The effects of repeated short-term hypoxia on exercise tolerance in patients at risk for, or with mild COPD were investigated. Eighteen patients (10 males, 8 females; 33-72 years) were randomly assigned in a double-blind fashion to receive 15 sessions of intermittent hypoxia (FiO(2): 0.15-0.12) or normoxia within 3 weeks. Three weeks of intermittent hypoxia increased total haemoglobin mass (+4% vs. 0%, p<0.05), total exercise time (+9.7% vs. 0%, p<0.05) and the exercise time to the anaerobic threshold (+13% vs. -7.8%, p<0.05) compared to controls. Changes in the total exercise time were positively related to the changes in total haemoglobin mass (r=0.59, p<0.05) and changes in the time to the anaerobic threshold were positively related to the changes in the lung diffusion capacity for carbon monoxide (r=0.48, p<0.05). Intermittent hypoxia treatment may be a valuable addition to therapy designed to improve exercise tolerance in patients at risk for, or with mild COPD.
Assuntos
Tolerância ao Exercício/fisiologia , Exercício Físico/fisiologia , Hipóxia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Limiar Anaeróbio/fisiologia , Análise de Variância , Monóxido de Carbono/metabolismo , Método Duplo-Cego , Teste de Esforço , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de TempoRESUMO
In recent years, mountain sports, especially ski mountaineering, are practised by increasing numbers. Although a high percentage of elderly with cardiovascular diseases is estimated, little is known about the real frequency of cardiovascular diseases among ski mountaineers. The goal of this study was to provide data on the frequency of cardiovascular diseases (coronary artery disease with and without myocardial infarction, hypertension, arrhythmias), collected among a representative sample of 937 ski mountaineers in the Austrian Alps. Data of 934 questionnaires were included into the evaluation. Regarding the whole sample, 5.8 % (95 % CI: 4.3 - 7.3 %) of the ski mountaineers are afflicted with at least one cardiovascular disease. The frequency of cardiovascular diseases is age dependent and more pronounced in men. Hypertension is the dominant cardiovascular disease in ski mountaineers. All persons with coronary artery disease with or without prior myocardial infarction and 79 % of the persons with cardiovascular diseases in general are males over the age of 40 years. Scientific research should provide the basis of an optimal risk management for this group of persons.
Assuntos
Doenças Cardiovasculares/epidemiologia , Montanhismo/fisiologia , Esqui/fisiologia , Adolescente , Adulto , Distribuição por Idade , Idoso , Áustria/epidemiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Amostragem , Distribuição por Sexo , Inquéritos e QuestionáriosRESUMO
Aerobic exercise performance decreases upon ascent to altitude whereas anaerobic performance remains unchanged. Although the effects of 1 - 3 wk of altitude acclimatization on both aerobic and anaerobic exercise performance have been well studied, the effects of short-term altitude acclimatization (i.e., 45 h) on these parameters have not been well defined. Therefore, both aerobic and anaerobic exercise performance was evaluated in five healthy men (51.4 +/- 7.7 years, 175 +/- 4.2 cm, and 73.8 +/- 6.1 kg) at low altitude (LA, 600 m), upon acute exposure (approximately 1 - 3 h) to 3200 m (HA1) and on the third day of altitude exposure (HA3, 3200 m). Subjects performed three consecutive exercise tests, separated by approximately 1 - 3 h of rest, of various durations (i.e., 30 s, 5 min, and 50 min) on a cycle ergometer in each environmental condition. Anaerobic cycling performance (i. e., 30 s) was the same at LA, HA1, and HA3. Aerobic cycling performance (i. e., 5 min and 50 min) was reduced by 12.0 and 11.3 %, respectively, upon acute exposure to altitude. There was no change in the 5-min cycling performance but the 50-min cycling performance improved by 5.7 % from HA1 to HA3 which implies a 50 % recovery of the initial loss. These findings are important for individuals going to high altitude for work, for athletic competition, or recreation.
Assuntos
Adaptação Fisiológica , Altitude , Hipóxia/fisiopatologia , Ergometria/métodos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Ventilação Pulmonar/fisiologia , Recuperação de Função Fisiológica/fisiologiaRESUMO
Psychiatric comorbidity is one of the key elements in chronic migraine (CM) management. Depression is particularly common in these patients, occurring in up to 85%. Preclinical studies have suggested that gamma-aminobutyric acid (GABA) levels may be decreased in animal models of depression. Also, clinical studies have reported low level in mood disorder patients for both plasma and cerebrospinal fluid (CSF) GABA. We hypothesized that low GABA levels in the brain might be related to the depression associated with CM. We studied 14 chronic migraine patients, with or without depression, compared to age-and sex-matched controls. CSF GABA levels were measured by HPLC. CSF GABA levels showed significant lower levels in depressed patients than those without depression. No difference was found when comparing patients versus controls. A GABA deficiency may be the underlying mechanism of depression in CM. Hence, preventive therapies modulating GABA neurotransmission could be used in CM associated with depression.
Assuntos
Encéfalo/metabolismo , Transtorno Depressivo/líquido cefalorraquidiano , Transtornos de Enxaqueca/líquido cefalorraquidiano , Ácido gama-Aminobutírico/líquido cefalorraquidiano , Ácido gama-Aminobutírico/deficiência , Encéfalo/fisiopatologia , Cromatografia Líquida de Alta Pressão , Doença Crônica , Comorbidade , Transtorno Depressivo/fisiopatologia , Feminino , Agonistas GABAérgicos/farmacologia , Agonistas GABAérgicos/uso terapêutico , Humanos , Masculino , Transtornos de Enxaqueca/fisiopatologia , Transtornos de Enxaqueca/psicologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/análiseRESUMO
Both preclinical and clinical data link glutamate to the migraine pathophisiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate levels have been reported in migraine patients. Chronic migraine is comorbid with several conditions. It has been recently shown chronic migraine comorbidity with fibromyalgia. The objective of this study was to study cerebrospinal fluid glutamate levels in chronic migraine patients with and without fibromyalgia. We studied 20 chronic migraine patients, with and without fibromyalgia, compared to age-sex matched controls. CSF glutamate levels were measured by HPLC. CSF glutamate demonstrated significantly higher levels in patients with fibromyalgia compared to those without fibromyalgia. Patients overall had higher CSF glutamate levels than controls. Mean pain score correlated with glutamate levels in chronic migraine patients. Tender points, the hallmark of fibromyalgia, can be considered as pressure allodynia, and is probably mediated by central sensitization, with increase in CSF glutamate levels. We postulate chronic migraine patients with fibromyalgia, in addition to have more disabling headaches, suffer from a more severe central sensitization process. This subtype of patients may respond to medications modulating glutamate receptors. Headache intensity correlate with glutamate levels in chronic migraine patients.
Assuntos
Fibromialgia/líquido cefalorraquidiano , Ácido Glutâmico/líquido cefalorraquidiano , Transtornos de Enxaqueca/líquido cefalorraquidiano , Adulto , Cromatografia Líquida de Alta Pressão , Doença Crônica , Feminino , Fibromialgia/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicaçõesRESUMO
Recently, mutations in the transcription factor CCAAT/ enhancer binding protein alpha (C/EBPalpha) have been described in acute myeloid leukemia (AML). We performed a mutational analysis of the C/EBPalpha gene in the myelodysplastic syndromes and AML with antecedent MDS. No mutations were found in patients with refractory anemia (0/27), refractory anemia with ringed sideroblasts (0/7), refractory anemia with excess of blasts (RAEB 0/16) or chronic myelomonocytic leukemia (CMML 0/5). One out of 13 patients with RAEB-T/AML secondary to MDS showed a mutation in the C/EBPalpha gene. In this patient a 4 bp insertion disrupted codon 69 in one allele. This novel +1 frame shift is predicted to result in a truncated protein of 107 amino acids. However, the dominant protein translated was the C/EBPalpha isoform p30, which was previously shown to inhibit the DNA-binding and transactivation properties of C/EBPalpha p42. Interestingly this mutation could not be detected at diagnosis in the initial RAEB and RAEB-T stage. The mutation appeared at relapse after chemotherapy for RAEB-T. We conclude that the C/EBPalpha mutation was not essential for the initial blast accumulation. The emergence of a bast clone carrying a C/EBPalpha mutation at relapse indicates that this mutation may confer a growth advantage in a myeloid cell with an established differentiation block.
Assuntos
Células da Medula Óssea/patologia , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Leucemia Mieloide Aguda/genética , Mutação , Síndromes Mielodisplásicas/genética , Adulto , Idoso , Anemia Refratária com Excesso de Blastos/genética , Anemia Refratária com Excesso de Blastos/patologia , Sequência de Bases , Primers do DNA , Progressão da Doença , Feminino , Humanos , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/patologia , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita SimplesRESUMO
To evaluate a potential therapeutic role for megakaryocyte growth and development factor (MGDF) in myelodysplastic syndromes (MDS) we compared the in vitro response of normal and myelodysplastic megakaryopoiesis to MGDF on bone marrow mononuclear cells from nine MDS patients and four healthy donors in a short term liquid culture system. The cells were incubated with MGDF alone (1 ng/ml, 10 ng/ml and 100 ng/ml) and in combination with 20 ng/ml stem cell factor, 2 U/ml erythropoietin (EPO) and 100 ng/ml interleukin-3 (IL-3). Cytospins were prepared after 4 days and 10 days for CD61 APAAP staining. In addition, the ploidy of propidium iodide stained CD61 positive cells were detected by flow cytometry. The CD61+ cell number significantly increased (13-fold after 4 days, 56-fold after 10 days of culture) when MGDF (100 ng/ml) was added to the normal bone marrow (NBM) cultures (P=0.0003; P=0.0001). In the MDS cultures the absolute number of endomitotic cells as well as the percentage of polyploid cells remained significantly lower than in NBM after 10 days (P=0.0001). The effect of MGDF on polyploidization of MDS cells was significantly dose dependent (P=0.0051). We found no correlation between peripheral platelet count, cellularity of the bone marrow, number of bone marrow megakaryocytes or FAB-subtype and response to MGDF. Additional administration of IL-3 resulted in a left-shift of megakaryopoiesis in both groups. Even though the response of myelodysplastic megakaryocytic progenitors to MGDF shows inter-individual variations, it is significantly impaired overall. Our data suggest that higher doses of MGDF may be able to ameliorate thrombocytopenia in a subgroup of MDS patients.
Assuntos
Megacariócitos/citologia , Síndromes Mielodisplásicas/patologia , Trombopoese/efeitos dos fármacos , Trombopoetina/fisiologia , Idoso , Estudos de Casos e Controles , Técnicas de Cultura de Células , Relação Dose-Resposta a Droga , Humanos , Pessoa de Meia-IdadeRESUMO
Platelet production is primarily regulated by the thrombopoietic cytokine thrombopoietin (TPO). In most cases thrombopoietin serum levels are determined by the rate of c-mpl receptor-mediated degradation after TPO uptake into platelets and megakaryocytes. The contribution of increased TPO protein synthesis by a translational mechanism was recently appreciated as the cause for hereditary thrombocythemia and will have to be elucidated in other conditions of thrombocytosis in association with increased TPO levels.