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Biomedical subjects

M T Zarrabeitia

Publications and source records attributed to M T Zarrabeitia.

At least 19 recordsLinked to original sources
PubMed2007

Klotho gene polymorphism and male bone mass.

The Klotho gene codes for a protein that is thought to influence the homeostasis of several tissues, including bone, as well as the aging process. Although the mechanism of action has not been fully elucidated, some studies in women have associated Klotho allelic variants to bone mineral density (BMD). The objective of this study was to determine the relationship of a common T/G polymorphism, resulting in a phenylalanine (F) to valine (V) substitution, with male bone mass. BMD was measured by dual-energy X-ray absorptiometry in 362 Spanish men aged 19-83 years. Klotho alleles were determined by a Taqman assay. Allele frequencies were 85% and 15% for the F and V alleles, respectively. In comparison with the most common FF genotype, young and middle-aged men (age less than 53 years) with FV/VV genotypes had higher age- and body mass index-adjusted BMD at the lumbar spine (1.059 +/- 0.017 vs. 1.016 +/- 0.011 g/cm(2), P = 0.036), the hip (1.077 +/- 0.017 vs. 1.033 +/- 0.011 g/cm(2), P = 0.028), and the calcaneus (0.599 +/- 0.125 vs. 0.547 +/- 0.108 g/cm(2), P = 0.012). Klotho alleles explained about 2-4% of BMD variance. However, Klotho genotype was not associated to BMD in older men. There were no Klotho-related differences in height, body weight, calcium intake, tobacco or alcohol consumption, or serum testosterone levels. In conclusion, these results suggest that allelic variants of Klotho constitute one of the genetic factors influencing BMD in male adults.

Adult↗
PubMed2006

MTHFR polymorphism and bone mineral density: meta-analysis of published studies.

The C677T (rs1801133) polymorphism of methylenetetrahydrofolate reductase (MTHFR) has been associated with bone status in some studies, but the results have been mixed. In order to have a better understanding of this issue, we performed a meta-analysis of studies about the association of the C677T polymorphism and bone mineral density (BMD). Eight studies analyzed the relationship with spine BMD. When their results were combined, individuals with TT genotype showed a small but significantly reduced BMD compared to those with TC and CC genotypes. The weighted mean difference (WMD) was 18.0 mg/cm2 (P = 0.001, 95% confidence interval [CI] 7.1-28.9), without statistical evidence for between-study heterogeneity (P = 0.28, I2 = 17%). Six studies analyzed femoral neck BMD. A test for heterogeneity was significant (P = 0.03, I2 = 56%). Individuals with TT alleles tended to have somewhat lower BMD, but the difference was not statistically significant. In random effects model, the WMD between the TT and TC/CC genotypes was 6.4 mg/cm2 (95% CI -7.8 to 21.2, P = 0.36). Total hip BMD was measured in four studies. They showed a significantly lower BMD in subjects with TT alleles: WMD 19.7 (95% CI 5.3-34.1) mg/cm2, P = 0.007, in comparison with TC/CC subjects. When we considered only studies on women, the WMD in BMD between TT and TC/CC genotypes was significant at the spine (22.1 mg/cm2, 95% CI 8.6-35.6; P = 0.001) and the femoral neck (15.5 mg/cm2, 95% CI 4.3-26.7; P = 0.007). There was no evidence for heterogeneity. The small number of studies did not allow a meaningful sex-stratified analysis of total hip BMD or a separate analysis of male data. In conclusion, the C677T polymorphism of the MTHFR gene is associated with small differences in BMD, at least in women.

Bone Density↗
PubMed2005

Mutation rates at Y chromosome specific microsatellites.

A collaborative work was carried out by the Spanish and Portuguese ISFG Working Group (GEP-ISFG) to estimate Y-STR mutation rates. Seventeen Y chromosome STR loci (DYS19, DYS385, DYS389I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS460, DYS461, DYS635 [GATA C4], GATA H4, and GATA A10) were analyzed in a sample of 3,026 father/son pairs. Among 27,029 allele transfers, 54 mutations were observed, with an overall mutation rate across the 17 loci of 1.998 x 10(-3) (95% CI, 1.501 x 10(-3) to 2.606 x 10(-3)). With just one exception, all of the mutations were single-step, and they were observed only once per gametogenesis. Repeat gains were more frequent than losses, longer alleles were found to be more mutable, and the mutation rate seemed to increase with the father's age. Hum Mutat 26(6), 520-528, 2005. (c) 2005 Wiley-Liss, Inc.

Age Factors↗
PubMed2005

Bone mass in young adults: relationship with gender, weight and genetic factors.

OBJECTIVES: To determine the relationship of the bone mass attained in young adults with anthropometric and genetic factors. DESIGN: Cross-sectional study of normal individuals. METHODS: We studied 341 healthy subjects between 22 and 45 years of age. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and correlated with body weight, height and nine polymorphisms in six genes involved in sex steroid metabolism (17-hydroxylase, aromatase and 5-reductase) and activity (oestrogen receptors (ER)-alpha and -beta, and androgen receptor). RESULTS: The BMD was higher in men than in women (spine: 1.048 +/- 0.120 vs. 1.034 +/- 0.112; hip: 0.907 +/- 0.131 vs. 0.822 +/- 0.104 g cm(-2), P < 0.001). However, the difference was due, at least in part, to the larger body size in men and diminished markedly after height adjustment. There was a negative correlation between age and hip BMD. Body weight was the single most influential factor on spine and hip BMD in both sexes, explaining 8-9% of BMD variance. Amongst the genetic factors studied, a common CA repeat polymorphism in ER-beta showed a significant association with BMD in women (P = 0.03 at the spine, and 0.008 at the hip). The relationship between ER-beta genotype and BMD persisted after adjustment by body weight and age, explaining a further 2-3% of BMD variance. Allelic variants of other genes studied were not related with BMD. CONCLUSIONS: Body weight and allelic variants of ER-beta are associated with BMD in young adults.

Absorptiometry, Photon↗
PubMed2004

X-linked microsatellites in two Northern Spain populations.

The X-chromosomal microsatellites HPRTB, DXS101, ARA, DXS7423, and DXS8377 were analysed by a pentaplex PCR in an expanded population sample from Cantabria and an independent sample of unrelated individuals from the Basque Country. Allele frequencies showed similar distributions, but minor variations were found for some loci.

Chromosomes, Human, X↗
PubMed2001

Accidental dichloromethane fatality: a case report.

A case of accidental dichloromethane poisoning by inhalation is presented. It is of interest that carboxyhemoglobin levels were within the normal range, suggesting that the narcosis and respiratory depression were due to the direct effect of DCM on the central nervous system. The accidental death was attributed to improper ventilation of vapors in the working area.

Adult↗
PubMed2000

[Multiple genetic typing (vitamin D receptors and estrogens) in the assessment of the risk of fractures].

BACKGROUND: Several studies suggested that some vitamin D receptor (VDR) and estrogen receptor (ER) polymorphisms influence bone mass. However, others did not confirm these results. This study was undertaken to determine if the genotypes revealed by the combined analysis of VDR and ER polymorphisms are associated with clinically significant differences in peak bone mass and the risk of osteoporotic fractures. PATIENTS AND METHODS: Restriction fragment length polymorphisms of VDR were determined with the enzymes Bsml, Apal, Taql, and Fokl. Enzymes Xbal and Pvull were used as polymorphic markers of the ER. The study group comprised 149 young control women (18-34 years), 66 postmenopausal controls, 99 women with hip fracture and 76 women with osteoporotic vertebral fractures. Bone mineral density (BMD) was measured by DEXA. RESULTS: We did not find significant differences in lumbar spine or hip BMD among young women with different genotypes (determined with either single or multiple polymorphic markers). Likewise, there were no differences in the frequency distributions of VDR or ER alleles between control and fractured women. The study had a 77% power to detect a fracture odds ratio of 2 in case of genotypes present in at least 15% of the population. CONCLUSIONS: These results suggest that the polymorphic markers used in this study do not have enough discriminant power to be clinically useful in the assessment of fracture risk.

Adult↗
PubMed2000

Hydrocephalus: a fatal late consequence of mumps encephalitis.

Common and usually self-limited diseases may occasionally have fatal consequences. Hydrocephalus is a very rare complication of mumps, with just a few cases reported in the literature. Here we report a fatal case of hydrocephalus presenting 19 years after mumps encephalitis. The long latency period between encephalitis and hydrocephalus-associated symptoms makes this case particularly interesting.

Adult↗
PubMed1997

[McArdle's disease in adults: clinical and genetic study].

McArdle's disease is a rare metabolic myopathy resulting from an absence of functional muscle glycogen phosphorylase that is inherited as an autosomal recessive condition. Recent molecular genetic studies have identified more than ten different mutations in patients with McArdle's disease, although a nonsense point mutation at codon 49 in exon 1 (R49X) accounts for approximately 85% of mutant alleles in American and British patients. We describe clinical, biochemical and genetic characteristics of five adults patients with McArdle's disease studied at our hospital during the last 10 years.

Adolescent↗
PubMed1996

Impairment of osteoblast growth by nitric oxide synthase inhibitors: an effect independent of nitric oxide and arginine transport inhibition.

The effect of various inhibitors of nitric oxide synthase (NOS) on three cell lines with osteoblastic phenotype was studied. N-Mono-methyl arginine (NMMA) inhibited the growth of MG63 and ROS 17/2.8 cells, and N-iminoethyl-ornithine (NIO) inhibited the growth of ROS 17/2.8. However, N-nitro-arginine (NA) and N-nitro-arginine-methyl ester (NAME) had no effect. None of the NOS inhibitors affected MC3T3 growth, in spite of blocking NO synthesis. NMMA and NIO also caused a marked decrease of arginine uptake by the three cell lines studied. These results indicate that some NOS inhibitors have antiproliferative effects which do not seem to be related to the inhibition of NOS activity or arginine uptake.

Animals↗
PubMed1995

Expression and functional role of nitric oxide synthase in osteoblast-like cells.

Nitric oxide synthases (NOS) are enzymes that produce nitric oxide (NO) from L-arginine in a reaction yielding citrulline as a coproduct. Nitric oxide modulates the activity of a wide variety of cells, but little is known about its effects on bone cells. In the present study we report that the NOS inhibitor NG-monomethyl-L-arginine (NMMA) induced a dose-dependent inhibitory effect on the proliferation of the osteoblast-like cell lines MG63 and ROS 17/2.8. The inhibitory effect was prevented by increasing L-arginine concentrations in the medium and by the NO donor sodium nitroprusside. Likewise, NMMA inhibited interleukin-6 secretion, independently of its effect on cell number. NOS expression by MG63 cells was confirmed by measuring their ability to metabolize radiolabeled L-arginine to citrulline. NOS bioactivity was detected in unstimulated cells, but was markedly increased by stimulating the cells with cytokines, lipopolysaccharide, or 1,25-dihydroxyvitamin D3. NOS activity was partially dependent upon the presence of calcium in the medium. Furthermore, constitutive-type NOS (c-NOS) and inducible-type NOS (i-NOS) mRNA expression was detected in ROS 17/2.8 cells after reverse transcription and polymerase chain reaction amplification. In conclusion, osteoblast-like cells express c-NOS and i-NOS, and NOS activity seems to play an important role in the regulation of cell proliferation and function.

Amino Acid Oxidoreductases↗
PubMed1995

Mechanisms controlling nitric oxide synthesis in osteoblasts.

Nitric oxide (NO) modulates the activity of a number of cell types, but little is known about its possible role in bone metabolism. In the present study we demonstrate that freshly isolated murine osteoblasts and an osteoblastic cell line express NO-synthase mRNA and release NO when stimulated with IL-1 or LPS, thus confirming the results of some recent reports using human and rat osteoblast-like cells. Synergistic effects were found between IL-1 and LPS or TNF. Enzyme induction was blocked by dexamethasone and IL-4. 1,25-dihydroxyvitamin D3 did not modify basal NO synthesis, but it markedly increased the cytokine-induced NO release. M-CSF, GM-CSF, IL-3, LIF, PTH, estradiol and calcitonin did not show significant effects on NO synthesis. NOS induction was blocked by various tyrosine-kinase inhibitors, geldanamycin and herbimycin A being the most potent. These results suggest that endogenous NO might participate in the regulation of bone remodeling at the local level, and may mediate some effects of vitamin D on bone. NO has recently been reported to inhibit osteoclastic bone resorption. The release of NO induced by bone-stimulating factors such as IL-1 may represent a protective mechanism helping to avoid excess resorption and preserve bone integrity in inflammatory conditions.

Amino Acid Oxidoreductases↗
PubMed1994

Age-related differences in cytokine secretion.

The aim of the present study was to compare cytokine secretion in healthy young and old subjects. Peripheral blood mononuclear cells were isolated from 55 healthy volunteers (aged 23-77 years) and cultured for 24 h in the presence or the absence of lipopolysaccharide (LPS) and 1,25-dihydroxyvitamin D3. Interleukin-1 beta (IL-1), tumor necrosis factor a (TNF) and prostaglandin E2 were measured in the culture supernatants with specific immunoassays. The unstimulated and LPS-stimulated production of IL-1 was significantly higher in the group of subjects older than 55 years than in the group aged less than 55 years. Likewise, there were positive correlations between age and the unstimulated and LPS-stimulated IL-1 secretion (r = 0.50 and 0.63, respectively, p < 0.01 in both cases). However, there were no age-related differences in the secretion of IL-1 in the presence of 1,25-dihydroxyvitamin D or in the secretion of TNF or prostaglandin E2 in any culture condition. These results suggest the existence of subtle abnormalities in cytokine secretion in healthy aged subjects, in comparison with younger individuals. In theory, the increased secretion of IL-1 might play a role in the pathophysiology of some diseases which are frequent in old people, such as osteoporosis.

Adult↗
PubMed1993

Interleukin-4 modulates osteoclast differentiation and inhibits the formation of resorption pits in mouse osteoclast cultures.

Interleukin-4 (IL-4) is a well known lymphocyte growth factor, but it may also modulate the activity of other cell types. In the present study we show that IL-4 exerts a potent dose-dependent inhibitory effect on the resorptive activity of mouse bone cells, measured as the number of resorption pits (decreased down to 14% of control, p < 0.001) or the total resorbed area (down to 20% of control, p < 0.001). The results obtained in bone marrow and unfractionated bone cell cultures indicate that such an effect is mainly due to an inhibition of osteoclast precursors differentiation, rather than to a reduced activity of mature osteoclasts, and is not mediated by the IL-4-induced release of other soluble inhibitory factors. Likewise, although IL-4 may stimulate M-CSF expression, its inhibitory effect on osteoclast recruitment was not prevented by anti-M-CSF antibodies, suggesting that it was not mediated by M-CSF. These results point out IL-4 as an potentially important regulatory factor of osteoclast differentiation.

Animals↗