Search PubMed⌕ Search

Biomedical subjects

J Gea

Publications and source records attributed to J Gea.

At least 19 recordsLinked to original sources
PubMed2006

Mitochondrial dysfunction in COPD patients with low body mass index.

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI(L)), eight COPD patients with normal body mass index (BMI(N)) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI(L) (2.2+/-0.6) compared with both BMI(N) (5.3+/-1.3) and controls (8.2+/-1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI(L) patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.

Aged↗
PubMed2006

Wood smoke exposure and risk of chronic obstructive pulmonary disease.

It was hypothesised that wood smoke exposure could be a risk factor for chronic obstructive pulmonary disease (COPD) in Spain. The present study was designed as a case-control study of 120 females requiring hospitalisation during 2001-2003 at Hospital del Mar (Barcelona, Spain). Cases were recruited from hospital records as females who had been admitted for an exacerbation of COPD. Controls were obtained from pulmonary function test laboratory consultations prior to a surgical intervention. All patients answered a standardised questionnaire. Exposure to wood or charcoal smoke was strongly associated with COPD after adjusting for age and smoking. The association between length of exposure and COPD suggested a dose-response pattern. Intensity of exposure in both summer and winter was also related to COPD. Wood or charcoal alone independently increased risk of COPD (odds ratio (OR) 1.8 and 1.5, respectively), but only the combination of both was statistically significant (OR 4.5). In conclusion, the present study shows a strong association between wood or charcoal smoke exposure and chronic obstructive pulmonary disease, supporting its existence not only in developing countries, but also in European countries, such as Spain. Further studies assessing whether this association also exists in other European societies are warranted.

Aged↗
PubMed2006

[Physiologic particularities of muscle impairments in the patient with COPD].

Patients with chronic obstructive pulmonary disease (COPD) frequently have skeletal muscle dysfunction, of either respiratory muscles or those located of the limbs. This dysfunction may appear even at relatively early stages and it conditions symptoms and patient's quality of life. In the case of respiratory muscles, factors that seem to determine muscle dysfunction are, particularly, changes in thorax configuration and an unbalance between decreased energy availability and increased energy demands by the muscle. However, respiratory muscles show signs of structural and metabolic adaptation to this situation, partially compensating the above-mentioned deleterious effects. However, at muscles of the limbs, particularly of the lower limbs, dysfunction seems to be essentially due to deconditioning by physical activity reduction. Structural changes in these muscles are involutional in nature. At both respiratory and peripheral muscles, other factors such as nutritional impairments, inflammation, oxidative stress, some drugs, and the presence of comorbidity seem to play a relevant role. All of them will condition both dysfunction and structural changes, which will be heterogeneous for the different muscle groups in each patient.

Humans↗
PubMed2005

Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects.

We hypothesized that resistive breathing of moderate to high intensity might increase diaphragm oxidative stress, which could be partially attenuated by antioxidants. Our objective was to assess the levels of oxidative stress in the dog diaphragm after respiratory muscle training of a wide range of intensities and whether N-acetyl-cysteine (NAC) might act as an antioxidant. Twelve Beagle dogs were anesthetized with 1% propophol, tracheostomized, and subjected to continuous inspiratory resistive breathing (IRB) (2 h/day for 2 wk). They were further divided into two groups (n = 6): NAC group (oral NAC administration/24 h for 14 days) and control group (placebo). Diaphragm biopsies were obtained before (baseline biopsy) and after (contralateral hemidiaphragm) IRB and NAC vs. placebo treatment. Oxidative stress was evaluated in all diaphragm biopsies through determination of 3-nitrotyrosine immunoreactivity, protein carbonylation, hydroxynoneal protein adducts, Mn-SOD, and catalase, using immunoblotting and immunohistochemistry. Both protein tyrosine nitration and protein carbonylation were directly related to the amount of the respiratory loads, and NAC treatment abrogated this proportional rise in these two indexes of oxidative stress in response to increasing inspiratory loads. A post hoc analysis revealed that only the diaphragms of dogs subjected to high-intensity loads showed a significant increase in both protein tyrosine nitration and carbonylation, which were also significantly reduced by NAC treatment. These results suggest that high-intensity respiratory loading-induced oxidative stress may be neutralized by NAC treatment during IRB in the canine diaphragm.

Acetylcysteine↗
PubMed2005

N-acetylcysteine increases manganese superoxide dismutase activity in septic rat diaphragms.

The antioxidant N-acetylcysteine (NAC) prevented sepsis-induced diaphragmatic dysfunction. As an indirect antioxidant NAC was shown to induce superoxide dismutase (SOD) activity in immune cells from endotoxaemic mice. The aim of this study was to assess whether NAC acts as an indirect antioxidant by inducing manganese (Mn)-SOD activity in the diaphragms of endotoxaemic rats, while preventing muscle dysfunction. A controlled study was conducted, in which protein carbonylation, Mn-SOD, catalase, and 3-nitrotyrosine immunoreactivity were detected using immunoblotting and immunohistochemistry in rat diaphragms. Six groups were studied for 24 h after a saline (control) or lipopolysaccharide (LPS; 20 mg.kg-1) i.p. injection in the absence and presence of NAC pre-treatment (either 1.5 or 3 mmol.kg(-1).24 h-1 for 7 days, oral administration). Diaphragm mitochondrial Mn-SOD activity and respiratory muscle function were also determined. Within 24 h, LPS induced maximal inspiratory pressure reduction, increasing diaphragmatic protein carbonylation and nitration. Pre-treatment with 3 mmol.kg-1 NAC clearly increased muscle Mn-SOD protein content and activity in both LPS- and saline-injected animals, while reducing protein carbonylation and nitration, and partially preventing the LPS-induced respiratory muscle dysfunction. Data produced from this study indicate that high doses of N-acetylcysteine induces manganese superoxide dismutase, as well as preserves its activity, possibly by preventing nitration of critical tyrosine residues of the enzyme.

Acetylcysteine↗
PubMed2004

[Analysis of respiratory muscle structure and tumor necrosis and insulin-like growth factor expression in chronic obstructive pulmonary disease: are samples valid if obtained during thoracotomy performed because of localized pulmonary neoplasia?].

OBJECTIVE: Various methods have been used to obtain samples to study the structure of human respiratory muscles and the expression of diverse substances in them. Samples are most often obtained from autopsies, from muscle biopsies during thoracotomy performed because of a localized pulmonary lesion (TLL), and from ambulatory thoracoscopic biopsy in patients free of comorbidity (AT). The disadvantage of the first 2 of these methods lies in the possibility of interference from factors related to the patient's death in the first case or from the disease that necessitated surgery in the second. Although AT is free from the disadvantages of the other 2 methods, it is impossible to obtain samples of the diaphragm the principal respiratory muscle with this procedure. The objective of this study was to analyze the fibrous structure of the external intercostal muscle of patients with chronic obstructive pulmonary disease and to quantify the expression of the principal inflammatory cytokine tumor necrosis factor alpha (TNF-alpha)- and of insulin-like growth factor (IGF-1) in the same muscle, comparing the results obtained with TLL and AT samples. METHODS: Prospective and consecutive samples were taken of the external intercostal muscle (fifth space, anterior axillary line) in 15 patients with chronic obstructive pulmonary disease (mean [SD] age 66 [6] years; forced expiratory volume in 1 second 49% [9%] of predicted; PaO2 75 [9] mm Hg). Samples were taken during TLL (8 patients, all with pulmonary neoplasms but carefully selected in order to rule out systemic effects) or TA (7 patients). Patients with serious comorbidity were excluded from the second group. Samples were processed for structural analysis of fibers (immunohistochemical and enzymatic histochemical) and genetic expression of TNF-alpha and IGF-1 (real-time polymerase chain reaction). RESULTS: No differences in the structure of fibers were found between the 2 groups. No differences were observed in the expression of TNF-alpha or IGF-1. CONCLUSIONS: Using rigorous criteria, the TLL method appears to be suitable for studying the structural characteristics and expression of inflammatory cytokines and growth factors in the external intercostal muscle. Moreover, it can also be inferred that TLL is probably also useful for obtaining samples of the diaphragm, a muscle which cannot currently be sampled by any alternative method.

Aged↗
PubMed2004

Glutathione and glutamate levels in the diaphragm of patients with chronic obstructive pulmonary disease.

Recently, decreased glutamate (Glu) and reduced glutathione (GSH) levels were reported in the quadriceps femoris of patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate whether Glu and GSH levels are also modified in the diaphragm of these patients. Nine male COPD patients (forced expiratory volume in one second (FEV1) range 28-68% of the predicted value) and seven male patients with normal pulmonary function (mean +/- SD FEV1 86 +/- 3% pred) submitted to thoracotomy were included. Biopsy specimens were taken from the diaphragm (both groups) and the quadriceps femoris (COPD group alone) in order to assess fibre size, myosin heavy chain expression, GSH levels and amino acid profile. The COPD group was characterised by preserved fibre size, a higher proportion of type I fibres (mean +/- SEM 70 +/- 3 versus 26 +/- 4%), and higher Glu and GSH content in the diaphragm compared to the quadriceps muscle. However, Glu and GSH levels were similar in diaphragm from the COPD and control groups. Glu level correlated with GSH level in both muscles. No significant correlation was found between Glu or GSH level and fibre size or proportions. This study shows that glutamate and reduced glutathione levels are preserved in the diaphragm of chronic obstructive pulmonary disease patients. Alterations in glutamate and reduced glutathione metabolism are muscle-specific in chronic obstructive pulmonary disease, affecting the quadriceps femoris but not the diaphragm. Glutamate and reduced glutathione levels are strongly interrelated in both muscles, independent of fibre type distribution and fibre size.

Aged↗
PubMed2004

Dyspnoea at rest and at the end of different exercises in patients with near-fatal asthma.

Blunted perception of dyspnoea under resistive loading has been observed in patients with a history of near-fatal asthma (NFA). The perception of dyspnoea at rest and at the end point of various exercises was assessed in such patients. Respiratory function and exercise capacity (6-min walking distance, incremental cycloergometry and inspiratory threshold loading) were assessed in seven NFA and eight non-NFA patients. Dyspnoea (Borg scale) was measured at rest and at the end point of the various exercises. Dyspnoea at rest was significantly lower in NFA patients. Although exercise tolerance was similarly reduced in both the NFA and non-NFA groups, dyspnoea at peak cycle exercise was significantly lower in the former (2.6+/-2 versus 6.1+/-3.8 (Borg scale; mean+/-SD)), who mainly (86%) stopped because of leg discomfort. A similar trend was observed in the 6-min walking distance and inspiratory threshold loading tests. Dyspnoea at peak exercise was the best indicator of the NFA condition, with a sensitivity of 100% and specificity of 63% for a Borg scale score of < or = 6. Perception of dyspnoea is blunted in near-fatal asthma patients at both rest and the end point of various forms of exercise. Dyspnoea at peak exercise is the best indicator of the near-fatal asthma condition.

Adolescent↗
PubMed2004

Relevance of assessing quadriceps endurance in patients with COPD.

The aims of this study were to investigate whether the impairment in endurance of limb muscles is a general finding in chronic obstructive pulmonary disease (COPD) patients, affecting even those with mild-to-moderate disease or relatively normal physical activity. In addition, this study aimed to determine the physiopathology of exhaustion in local endurance tests and whether the reduction in quadriceps endurance can be predicted from muscle strength measurements. A total of 75 volunteers were assigned to one of two groups according to pulmonary function tests: COPD patients or healthy age-matched controls. Functional assessment included both quadriceps strength (maximum voluntary contraction (QMVC)), and quadriceps endurance (contractions against a load equivalent to 10% QMVC until task failure or for up to a limiting time of 30 min (QTlim)). COPD patients showed a decrease of approximately 43%, in QMVC and approximately 77% in QTlim compared with controls. Task failure occurred only in COPD patients and was due to muscle fatigue, since limiting symptoms were associated with a decrease in the median frequency of quadriceps electromyographical signal and a reversible decrease in QMVC. The impairment in skeletal muscle endurance was present even in patients with mild-to-moderate airflow obstruction and individuals with relatively normal physical activity, and was irrespective of lung function variables, anthropometrical data or quadriceps strength. Peripheral muscle endurance was impaired in chronic obstructive pulmonary disease patients, even in those with relatively normal physical activity and mild-to-moderate airflow obstruction. This impairment associated with an early onset of muscle fatigue and could not be predicted from the severity of the disease or the reduction in quadriceps strength.

Age Distribution↗
PubMed2002

[Basic structure of respiratory and peripheral muscles in the beagle dog].

BACKGROUND: The dog is one of the most widely used animals in studies of respiratory physiopathology, mainly because of its physiological characteristics. However, ethical and legal constraints are placed on the use of some species in our context. OBJECTIVE: We studied the underlying structural features of respiratory and peripheral muscles in the beagle dog in order to suggest reference values for future studies. METHOD: Fourteen young beagles were selected. Samples were taken from the costal diaphragm (DFG), external intercostal (EI) and vastus medialis (VM) muscles. We analyzed fiber percentages and sizes (immunohistochemistry, using myosin heavy chain [MyHC (monoclonal antibodies), percentages and absolute number of MyHC isoforms (electrophoresis and ELISA), and level of membrane damage (immunohistochemistry, using anti-fibronectin monoclonal antibodies). RESULTS: In the EI muscle, type I fibers were larger (by 20%) than type II fibers. Fibers resistant to fatigue (type I) predominated greatly over fast contraction fibers (type II) in all three muscles analyzed (DFG 57% 11% vs. 45% 12%; EI 58% 5% vs. 43% 5%; and VM 70% 8% vs. 34% 7 %). Few hybrid fibers (co-expression of fast and slow MyHC) were found and their percentages were similar in all three muscles. The absolute expression of MyHC was greater in the VM than in the respiratory muscles, with a relative predominance of the MyHC I isoform in the DFG and VM muscles and a similar tendency in the EI muscle. Membrane damage was very slight in all three muscles. CONCLUSIONS: The phenotype characteristics of respiratory and peripheral muscles in the beagle correspond to what we would expect functionally for a breed initially selected for hunting, with minimal lesions under normal circumstances, a predominance of fibers and proteins that are resistant to fatigue, and larger fibers in the EI, a muscle that plays a role in respiration in dogs.

Animals↗
PubMed2002

[Interleukin 10 and tumor necrosis factor alpha gene expression in respiratory and peripheral muscles. Relation to sarcolemmal damage].

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in loss of muscle mass in chronic obstructive pulmonary disease and other consumptive processes. TNF-alpha production would be related to inflammation arising from pulmonary disease itself or, alternatively, from smoking, and would be carried to the muscle through the blood stream. However, it has also been suggested that TNF-alpha may be expressed directly in muscle tissue. Regardless the site of production of TNF-alpha, its relation to subsequent muscle damage is unclear. OBJECTIVE: We studied the expression of TNF-alpha and an interleukin inhibitor of its production (IL-10) in the main respiratory muscles and a peripheral muscle in the dog. METHOD: Nine young, male Beagle dogs were included. From all animals we obtained a biopsy of the diaphragm (Dph) and external intercostal (ExtI) muscles and a leg muscle (internal vastus of the quadriceps, IntV). TNF-alpha and IL-10 gene expressions were measured through the analysis of messenger RNA levels, using reverse transcription and polymerase chain reaction. We also assessed sarcolemmal damage using intracellular fibronectin detection (immunohistochemistry). RESULTS: The expression of both cytokines showed wide interindividual variability. On the one hand, TNF-alpha (was very low in Dph and ExtI (0.02 0.03 and 0.05 0.06 a.u., respectively), but relatively high in the IntV (0.14 0.08 a.u.). IL-10 expression, on the other hand was low in the Dph (0.06 0.05 a.u.) and slightly higher in the ExtI (2.7 1.9 a.u., p < 0.01) and IntV (1.6 1.7 a.u.). Sarcolemmal damage was minimal in all three muscles and was related to TNF-alpha expression in the peripheral muscle (r = 0.682, p < 0.05). CONCLUSIONS: 1) TNF-alpha and IL-10 appear to be constitutively expressed within the skeletal muscle in dogs. 2) Basal TNF-alpha expression is lower in respiratory muscles than in peripheral muscles. 3) The expression in the latter is related to membrane damage.

Animals↗
PubMed2002

[Low-weight syndrome associated with COPD in our setting].

UNLABELLED: The high prevalence of chronic obstructive pulmonary disease (COPD) has considerable economic and health-related impact. The consequences arise largely from limitations on a patient's activity and shortened life expectancy. Low body weight has recently been implicated as a factor affecting limitations. Although the reason is not clear, weight loss appears to affect many patients (from 25 to 35% in different series), at least in Europe and North America. However, the situation is thought to be different in the Mediterranean area. OBJECTIVE: To estimate the prevalence of the low weight syndrome in patients with COPD in our area. METHODS: COPD patient characteristics monitored by our laboratory over the last two years (2000 and 2001) were reviewed. RESULTS: The prevalence of a body mass index (BMI) less than 20 kg/m2 was only 6.6% among the 3,126 patients studied. That percentage fell to 3.1% with a cutoff of 18 kg/m2. The figure was even more striking if we consider that half the patients had severe disease (FEV1 < 50% of reference). BMI was directly related to FEV1/FC and CO transfer. CONCLUSIONS: These results suggest that COPD patients in our geographic area have characteristics that distinguish them from those previously described in other countries. Specifically, the prevalence of low weight syndrome in our area appears to be lower. However, larger studies should be performed to confirm this finding.

Aged↗
PubMed2002

Procion orange tracer dye technique vs. identification of intrafibrillar fibronectin in the assessment of sarcolemmal damage.

BACKGROUND: The use of Procion orange dye (POD) is one of the most widely accepted techniques to assess sarcolemmal damage. This phenomenon has been related to functional adaptation in skeletal muscles. The POD method includes intravenous injection of this colorant in vivo, enabling its identification inside those fibres with membrane leaks (fluorescence). However, the safety of the use of POD has not been proven. AIM: This study was designed to compare POD with a safer alternative, involving the identification of intracellular fibronectin using specific antibodies. METHOD: Eight Swiss mice were submitted to electrical stimulation of the lower limbs at different frequencies (10-80 Hz). Subsequently, the POD solution was infused, and samples from the vastus medialis muscle were obtained 24 h later. Samples were processed and serial sections were analysed using immunohistochemistry (monoclonal antibodies against fibronectin) and epifluorescence microscopy. RESULTS: Ninety-eight per cent of the fibres were equally classified by both techniques, which in addition showed good correlation (percentages of damaged fibres, r = 0.998, P < 0.001) and concordance (R1 = 0.82) in quantitative terms. CONCLUSIONS: Although the two techniques compared here are based on different principles, both are comparable in assessing sarcolemmal damage. This would facilitate comparisons between human and experimental studies. In addition, the fibronectin technique appears to be a suitable alternative for long-term studies including repeated biopsies.

Animals↗
PubMed2002

Expiratory muscle endurance in chronic obstructive pulmonary disease.

BACKGROUND: A reduction in expiratory muscle (ExM) endurance in patients with chronic obstructive pulmonary disease (COPD) may have clinically relevant implications. This study was carried out to evaluate ExM endurance in patients with COPD. METHODS: Twenty three patients with COPD (FEV(1) 35 (14)% predicted) and 14 matched controls were studied. ExM endurance was assessed using a method based on the use of an expiratory threshold valve which includes two steps. In step 1 the load is progressively increased (50 g every 2 minutes) until task failure is reached, and the pressure generated against the highest tolerated load is defined as the maximal expiratory sustainable pressure (Pthmax). In step 2 subjects breathe against a submaximal constant load (80% of Pthmax) and the time elapsed until task failure is termed the expiratory endurance time (Tth(80)). In addition, the strength of peripheral muscles (handgrip, HGS) and respiratory muscles (maximal inspiratory and expiratory pressures, PImax and PEmax, respectively) was evaluated. RESULTS: Patients with COPD had lower ExM strength and endurance than controls: PEmax 64 (19)% predicted v 84 (14)% predicted (mean difference 20%; 95% confidence intervals (CI) 14 to 39); Pthmax 52 (27) v 151 (46) cm H(2)O (mean difference 99, 95% CI 74 to 123); and Tth(80) 9.4 (6.3) v 14.2 (7.4) min (mean difference 4.8, 95% CI 1.0 to 10.4; p<0.01 for all). Interestingly, ExM endurance directly correlated with both the severity of airways obstruction (Pthmax with FEV(1), r=0.794, p<0.01) and the reduction in strength observed in different muscle groups (Pthmax with HG, PImax or PEmax, r=0.550, p<0.05; r=0.583, p<0.001; and r=0.584, p<0.001, respectively). CONCLUSIONS: ExM endurance is decreased in patients with COPD. This impairment is proportional to the severity of the disease and is associated with lower strength in different muscle groups. This suggests that systemic effects are implicated in the impairment observed in ExM function.

Electromyography↗
PubMed2001

Injury of the human diaphragm associated with exertion and chronic obstructive pulmonary disease.

Injury of the diaphragm may have clinical relevance having been reported in cases of sudden infant death syndrome or fatal asthma. However, examination of diaphragm injury after acute inspiratory loading has not been reported. The purpose of this study was to determine whether an acute inspiratory overload induces injury of the human diaphragm and to determine if diaphragm from chronic obstructive pulmonary disease (COPD) is more susceptible to injury. Eighteen patients with COPD and 11 control patients with normal pulmonary function (62 +/- 10 yr) undergoing thoracotomy or laparotomy were studied. A threshold inspiratory loading test was performed prior to surgery in a subset of seven patients with COPD and five control patients. Samples of the costal diaphragm were obtained during surgery and processed for electron microscopy analysis. Signs of sarcomere disruption were found in all diaphragm samples. The range of values of sarcomere disruption was wide (density: 2-45 abnormal areas/100 microm(2); area fractions: 1.3-17.3%), significantly higher in diaphragm from patients with COPD (p < 0.05) and with the greatest injury after inspiratory loading. We conclude that sarcomere disruption is common in the human diaphragm, is more evident in patients with COPD, and is higher after inspiratory loading, especially in the diaphragm of those with COPD.

Aged↗