Biomedical subjects

F Gómez-Gallego

Publications and source records attributed to F Gómez-Gallego.

12 recordsLinked to original sources

PubMed2006

Mobilisation of mesenchymal cells into blood in response to skeletal muscle injury.

Mesenchymal cells recruited to damaged tissues must circulate through the bloodstream. The absolute numbers of circulating mesenchymal stem cells (cMSCs) in two different models of acute and chronic skeletal muscle injury were determined. cMSCs were present in significantly higher numbers in both models than in healthy controls. These results support the hypothesis that MSCs are mobilised into the bloodstream after skeletal muscle tissue damage. These two models (acute and chronic) would be of value in the search for molecular mediators of mobilisation of MSCs into the circulation.

Adult↗

PubMed2006

ACTN3 genotype in professional endurance cyclists.

The Z-disk protein alpha-actinin-3 is only expressed in type II muscle fibres, which are responsible for generating forceful contractions at high velocity. Despite the evolutionary conservation of alpha-actinin-3, approximately one in every five Caucasians of European ancestry is totally deficient in this protein, due to homozygosity for a R577X polymorphism in the ACTN3 gene. This, together with the results of recent research on elite athletes, suggests that the "null" XX polymorphism might confer some advantage to endurance performance events. To test this hypothesis, we studied the frequency distribution of R577X genotypes in a group of 50 top-level male professional cyclists (26.9 +/- 0.4 yrs [mean +/- SEM]; VO2max: 73.5 +/- 0.8 ml x kg (-1) x min (-1)). Their results were compared with those of a group of 52 Olympic-class male endurance runners (26.8 +/- 0.6 yrs; VO2max: 73.3 +/- 0.8 ml x kg (-1) x min (-1)) and 123 healthy, sedentary male controls. All subjects were Caucasian, and of European ancestry. No significant differences (p > 0.05) were found between groups: RR: 28.5 %; RX: 53.6 % and XX: 17.9 % in controls; RR: 28.0 %; RX: 46.0 % and XX: 26.0 % in cyclists; and RR: 25.0 %; RX: 57.7 %; XX: 17.3 % in runners). No differences were found in indices of endurance performance (VO2peak or ventilatory thresholds) between athlete carriers of each R577X genotype. In summary, although the alpha-actinin-3 deficient XX genotype may be detrimental for sprint performance in humans, the R577X polymorphism of the ACTN3 gene does not appear to confer an advantage on the ability of male athletes to sustain extreme endurance performance.

Actinin↗

PubMed2006

Does the C34T mutation in AMPD1 alter exercise capacity in the elderly?

Ageing does affect functional capacity through several changes at the peripheral muscle level that impair the muscles capacity to produce energy and generate force. The skeletal muscle-specific isoform of AMP deaminase (AMPD) plays an important regulatory role in muscle metabolism and in determining energy charge. Since nearly 20 % of the general Caucasian population is heterozygous (CT) for the most common C34T mutation of the gene (AMPD1) encoding for this enzyme, it would be worthwhile to study if such a condition further increases the effects of ageing. Twenty-one women (61 - 80 yrs) served as subjects, and depending on the results of previous genotyping, were assigned to a group with the C34T mutation (heterozygous; n=4; mean+/-SEM age: 71+/-1 yrs) or with no mutation (n=17; 68+/-1 yrs). Several indices of maximal (peak oxygen uptake [V.O (2 peak)], peak power output) and submaximal endurance performance (ventilatory threshold, mechanical efficiency) and functional tests (one-mile walk test and a specific test of lower-body functional performance [sit-stand test]) were compared between the two groups. No significant differences were found in exercise capacity between both groups, e. g. V.O (2 peak) of 19.1+/-1.0 vs. 20.1+/-1.9 ml . kg (-1) . min (-1), V.O (2) at the VT of 11.9+/-0.6 vs. 12.9+/-1.0 ml . kg (-1) . min (-1), or time to complete the one-mile walk test (951+/-18 s vs. 962+/-61 s) and sit-stand test (9.9+/-0.2 vs. 9.2+/-0.2) (no mutation vs. C34T mutation, respectively). Although more research is necessary, it seems that the C34T mutation of the AMPD1, at least in heterozygous individuals, does not affect functional capacity in the elderly.

AMP Deaminase↗

PubMed2006

Changes in mucosal and humoral atopic-related markers and immunoglobulins in elite cyclists participating in the Vuelta a España.

Atopic-related factors, humoral and mucosal immunoglobulins (Ig), and cortisol were measured in 17 professional cyclists competing in the 2003 Vuelta a España (a three-week multi-stage race). Venous blood and saliva samples were obtained the morning before the start of the race (T0), on the first rest day after 10 days of racing (T1), and before the start of the last stage after 21 days of racing (T2). Atopic-related factors, IgE, eosinophil cationic protein (ECP), and eosinophils, were significantly altered during the race. Serum IgE (T1: + 10 %) and ECP (salivary, T1: 113 % and serum, T2: 155 %) were significantly increased, while eosinophils (T1: - 32 %, T2: - 55 %) were significantly lower, than pre-race levels. Salivary sIgA secretion rate was significantly decreased at T2 (- 36 %). Pearson product-moment correlations revealed a modest correlation between salivary sIgA and salivary ECP (T1: r = 0.30; T2: r = 0.48; p < 0.01). Serum IgM, total IgG, IgG1, IgG2, IgA levels, at T1 and T2, and cortisol at T2, were significantly lower than pre-race levels. In conclusion, the elevation in IgE and ECP suggests an up-regulation of atopic-related factors in professional cyclists participating in the Vuelta a España. The correlation between salivary sIgA and salivary ECP indicates a role for sIgA in mediating mucosal inflammation. The alterations in Ig levels may indicate Ig isotype switching. An increasing state of hormonal fatigue may have influenced the observed immune alterations.

Analysis of Variance↗

PubMed2006

Exercise capacity in a 78 year old patient with McArdle's disease: it is never too late to start exercising.

The case is reported of a 78 year old man with McArdle's disease and a history of treated coronary heart disease. Despite the pre-exercise administration of sucrose allowing the patient to exercise with normal physiological responses, and without typical McArdle's symptoms or biochemical evidence of muscle damage, his exercise capacity was very low (V(O2)peak = 10.7 ml/min/kg), probably attributable to his lifetime of sedentary living. The data suggest that, with pre-exercise sucrose administration, such patients may be candidates for systematic reconditioning, which may improve functional capacity and quality of life.

Aged↗

PubMed2005

Association of the genetic polymorphisms of the renin-angiotensin system with kidney graft long-term outcome: preliminary results.

Recent studies have demonstrated some association between the renin-angiotensin system (RAS) activity and the development and progression of different entities as diabetes mellitus (DM) or chronic allograft nephropathy. To investigate these associations, we studied some gene polymorphisms of RAS in a group of renal transplant recipients. We retrospectively analyzed 42 patients who underwent a primary renal transplantation for 2 years. A subgroup of 23 patients (55%) was diagnosed with postransplant DM in accordance with American Diabetes Association 2001 criteria. We studied two RAS gene polymorphisms: the angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensinogen (AGTM235T). Genotyping was performed by DNA purification and amplification with a polymerase chain reaction technique. The distributions of genotypes were ACE DD, ID, II: 33%, 48%, 19%; and AGT TT, MT, MM: 15%, 45%, 40%, respectively. We observed a progressive loss in renal function measured by creatinine clearance (Cockroft) in D-allele carriers (DD+ID) between the first and the second transplantation year: 65.3 +/- 4.3 vs 59.8 +/- 4.6 mL/min (P = 0.02); that was not seen in II patients: 68.8 +/- 4.6 vs 68.4 +/- 4 mL/min (P = 0.87). Fifty percent of D-allele carriers developed DM vs 25% of non-D-allele carriers (P = 0.19). Eighty-three percent of homozygous patients for the AGT-TT allele developed DM vs 35% of non TT patients (P = 0.04). There were no significant differences regarding recipient demographic characteristics, type of donor, number and severity of acute rejections, and immunosuppressant treatment between the groups. In conclusion, ACE D-allele seems to be associated with a poorer kidney graft long-term outcome. ACE D and AGT T alleles may be implicated in glucose metabolism disorders after transplantation.

DNA↗

PubMed2005

[Genetic susceptibility to the development of acute alcoholic hepatitis: role of genetic mutations in dehydrogenase alcohol, aldehyde dehydrogenase and cytochrome P450 2E1].

OBJECTIVE: Analyze the frequencies of genetic mutation in alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) and cytochrome P450 2E1 (CYP2E1) and establish their possible association with the development of acute alcoholic hepatitis (AAH). METHODOLOGY: Case-control study in a total of 85 Spanish patients. We distinguish three groups (one case group and two control groups) based on hepatic histological lesion and alcohol consumption: controls (group 1: teetotalers; group 2: drinkers without AAH; cases: group 3: drinkers with AAH). Case diagnosis was established based on the presence of polymorphonuclear leukocyte infiltrate in histological study. We analyzed the presence of the genetic mutations R47H and R369C (ADH2), E487K (ALDH2) and mutation Rsa I of CYP2E1 (allele c2) by polymerase chain reaction (PCR) and capillary electrophoresis. RESULTS: The allele c2 of CYP2E1 was found in 10%, 16% and 50% of the groups 1, 2 and 3 patients, respectively. Presence of the mutation Rsa I showed influence on the development of AAH (odds ratio [OR]: 3.63; confidence interval (95% [CI]: 0.88-15.02). CONCLUSIONS: The data suggest a possible association between the presence of the Rsa I of CYP2E1 and the development of AAH in patients with chronic alcohol consumption.

Acute Disease↗

PubMed2004

Mutations in the hereditary haemochromatosis gene HFE in professional endurance athletes.

BACKGROUND: Hereditary haemochromatosis, a disease that affects iron metabolism, progresses with a greater or lesser tendency to induce iron overload, possibly leading to severe organ dysfunction. Most elite endurance athletes take iron supplements during their active sporting life, which could aggravate this condition. OBJECTIVE: To determine the prevalence and discuss potential clinical implications of mutations of HFE (the gene responsible for hereditary haemochromatosis) in endurance athletes. METHODS: Basal concentrations of iron, ferritin, and transferrin and transferrin saturation were determined in the period before competition in 65 highly trained athletes. Possible mutations in the HFE gene were evaluated in each subject by extracting genomic DNA from peripheral blood. The restriction enzymes SnaBI and BclI were used to detect the mutations 845G-->A (C282Y) and 187C-->G (H63D). RESULTS: Our findings indicate a high prevalence of HFE gene mutations in this population (49.2%) compared with sedentary controls (33.5%). No association was detected in the athletes between mutations and blood iron markers. CONCLUSIONS: The findings support the need to assess regularly iron stores in elite endurance athletes.

Adult↗

PubMed2000

Structural defects underlying protein dysfunction in human glucose-6-phosphate dehydrogenase A(-) deficiency.

The enzyme variant glucose-6-phosphate dehydrogenase (G6PD) A(-), which gives rise to human glucose-6-phosphate dehydrogenase deficiency, is a protein of markedly reduced structural stability. This variant differs from the normal enzyme, G6PD B, in two amino acid substitutions. A further nondeficient variant, G6PD A, bears only one of these two mutations and is structurally stable. In this study, the synergistic structural defect in recombinant G6PD A(-) was reflected by reduced unfolding enthalpy due to loss of beta-sheet and alpha-helix interactions where both mutations are found. This was accompanied by changes in inner spatial distances between residues in the coenzyme domain and the partial disruption of tertiary structure with no significant loss of secondary structure. However, the secondary structure of G6PD A(-) was qualitatively affected by an increase in beta-sheets substituting beta-turns related to the lower unfolding enthalpy. The structural changes observed did not affect the active site of the mutant proteins, since its spatial position was unmodified. The final result is a loss of folding determinants leading to a protein with decreased intracellular stability. This is suggested as the cause of the enzyme deficiency in the red blood cell, which is unable to perform de novo protein synthesis.

Amino Acid Sequence↗

PubMed1999

Molecular basis and enzymatic properties of glucose 6-phosphate dehydrogenase volendam, leading to chronic nonspherocytic anemia, granulocyte dysfunction, and increased susceptibility to infections.

We have investigated the blood cells from a woman with a low degree of chronic nonspherocytic hemolytic anemia and frequent bacterial infections accompanied by icterus and anemia. The activity of glucose 6-phosphate dehydrogenase (G6PD) in her red blood cells (RBCs) was below detection level, and in her leukocytes less than 3% of normal. In cultured skin fibroblasts, G6PD activity was approximately 15% of normal, with 4- to 5-fold increased Michaelis constant (Km) for NADP and for glucose 6-phosphate. Activated neutrophils showed a decreased respiratory burst. Family studies showed normal G6PD activity in the RBCs from all family members, including both parents and the 2 daughters of the patient. Sequencing of polymerase chain reaction (PCR)-amplified genomic DNA showed a novel, heterozygous 514C-->T mutation, predicting a Pro172-->Ser replacement. Analysis of G6PD RNA from the patient's leukocytes and fibroblasts showed only transcripts with the 514C-->T mutation. This was explained by the pattern of X-chromosome inactivation, studied by means of the human androgen receptor (HUMARA) assay, which proved to be skewed in the patient, her mother, and one of the patient's daughters. Thus, the patient has inherited a de novo mutation in G6PD from her father and an X-chromosome inactivation determinant from her mother, causing exclusive expression of the mutated G6PD allele. Purified mutant protein from an Escherichia coli expression system showed strongly decreased specific activity, increased Km for NADP and for glucose 6-phosphate, and increased heat lability, which indicates that the defective phenotype is due to 2 synergistic molecular dysfunctions: decreased catalytic efficiency and protein instability.

Adult↗

PubMed1996

Unproductive folding of the human G6PD-deficient variant A-.

Human glucose-6-phosphate dehydrogenase (G6PD) deficiency almost invariably results from the presence of missense mutations in the X-linked gene encoding G6PD. The common African deficient variant G6PD A- differs from the normal G6PD B by two amino acid substitutions. Only one of these mutations is found on its own, resulting in the nondeficient variant G6PD A. Deficiency is always associated with decreased G6PD activity in red cells, leading to a variety of clinical manifestations. A group of deficient variants, including A-, have near-normal affinity for the substrates G6P and NADP. In these cases, deficiency is caused by a decreased number of catalytically active molecules per cell due to intracellular instability of the mutated G6PD, although the mechanism for this in vivo instability is unknown. Here we report that in vitro folding of the A- variant mainly renders partially folded polypeptides that do not undergo the dimerization required for activity. Under the same conditions, the nondeficient variants B and A undergo folding to produce active dimers with normal mobilities in native gels and normal kinetic properties. The loss of intrinsic folding determinants in the A- variant may underlie the mechanism of its in vivo instability.

Africa↗

PubMedDate not supplied

Is there an association between ACE and CKMM polymorphisms and cycling performance status during 3-week races?

In this paper, we examine the association between polymorphisms of the angiotensin-converting enzyme (ACE) and muscle-specific creatine kinase (CKMM) genes, and the actual performance status observed in professional cyclists capable of completing a classic tour stage race such as the Giro d'Italia, Tour de France, or Vuelta a España. To accomplish this, we compared the frequencies of the ACE and CKMM genotypes/alleles in 50 top-level Spanish professional cyclists that have completed at least one of these events to 119 sedentary controls, and 27 elite (Olympic-class) Spanish runners. The genetic polymorphism at the CK-MM locus was detected with the NcoI restriction endonuclease. The results of our study showed that the proportion of the DD genotype was higher in cyclists (50.0 %) than in the other two groups (p<0.05), the proportion of the ID genotype was higher in controls (46.2 %) than in the other two groups (p<0.05), and the proportion of the II genotype was higher in runners (40.7 %) than in the other two groups (p<0.05). The proportion of the D allele was higher in both cyclists (65.0 %) and controls (57.6 %) than in runners (46.3 %) (p<0.001), whereas the proportion of the I allele was higher in runners than in the other two groups (p<0.001). No statistical differences were found for CKK-MM- NcoI. We conclude that in top-level professional cyclists capable of completing a classic 3-wk tour race, the frequency distribution of the D allele and the DD genotype seems to be higher than in other endurance athletes such as elite runners (in whom the I allele is especially frequent).

Adult↗