Biomedical subjects

I Arribas

Publications and source records attributed to I Arribas.

At least 19 recordsLinked to original sources

PubMed1998

Cyclosporine A nephrotoxicity: role of thromboxane and reactive oxygen species.

The main adverse effect of cyclosporine A (CyA) is nephrotoxicity. CyA increases urinary concentrations of thromboxane A2 (TXA2), a potent vasoconstrictor that can be involved in kidney failure induced by CyA. Furthermore, it has been postulated that a relationship exists between oxygen free radicals and the synthesis of arachidonate metabolites in experimental models of CyA nephrotoxicity. We studied the effect of vitamin E (VitE), an oxygen free radical scavenger, on renal function, on glomerular synthesis of thromboxane B2 (TXB2), and on free radicals in rats treated with CyA. Four groups of male Wistar rats were studied: (1) a control group; (2) a group given VitE at 0.05 mg/dl in drinking water for 25 days; (3) a group given CyA at 50 mg/kg body weight/day orally for 10 days; and (3) a group given Vit E + CyA, in which rats were provided with drinking water containing VitE for 15 days and afterwards were treated with VitE and CyA for 10 days. Renal function parameters and glomerular synthesis of TXB2, superoxide anion (02.-), malondialdehyde (MDA), and hydrogen peroxide (H202) were evaluated. CyA decreased body weight, caused deterioration of kidney function and increased glomerular synthesis of TXB2, O2.-, MDA, and H202. Pretreatment with VitE prevented the effects of CyA on kidney function and decreased glomerular synthesis of these mediators. In conclusion, CyA induced glomerular synthesis of reactive oxygen species (ROS) and TxB2. Pretreatment with VitE inhibited acute renal failure induced by CyA, probably by scavenging free radicals and by inhibiting the synthesis of TXB2.

Animals↗

PubMed1996

New evidence that serum beta(2)-microglobulin behaves as a biological marker of bone remodelling in women.

Having observed that serum beta(2)-microglobulin concentration correlates with serum tartrate-resistant acid phosphatase (TRAP) concentration in postmenopausal osteoporosis, and that metacarpal endosteal diameter is dependent on bone resorption, we correlated the two biochemical parameters with the radiographic parameter to determine if beta(2)-microglobulin behaves like a biological marker of bone remodelling. In 105 women (mean age 68 +/- 4 years) consisting of 60 normal postmenopausal women and 55 osteoporotic postmenopausal women, there was a significant positive correlation between metacarpal endosteal diameter and these two biochemical values (r = 0.66 with beta(2)-microglobulin and r = 0.68 with TRAP in the osteoporotic postmenopausal women; r = 0.48 with beta(2)-microglobulin and r = 0.56 with TRAP in the normal postmenopausal women; P < 0.001 for all comparisons). All three measurements were significantly higher (P < 0.001) in the osteoporotic postmenopausal women than in the normal postmenopausal women. These findings show that serum beta(2)-microglobulin behaves like a biological marker of remodelling.

Acid Phosphatase↗

PubMed1995

Beta-2-microglobulin in diseases with high bone remodeling.

Beta2-microglobulin has been observed to behave as a biological marker of bone remodeling. We measured beta2-microglobulin and tartrate-resistant acid phosphatase (TRAP), a specific biological marker of bone remodeling, in 225 women: healthy premenopausal controls, healthy postmenopausal control, and patients with diseases characterized by enhanced bone turnover (postmenopausal osteoporosis, primary hyperparathyroidism, primary hyperthyroidism, polyostotic Paget's bone disease), and in other Paget's group before and after calcitonin treatment. Beta2-microglobulin levels differed significantly between the healthy premenopausal women (n = 20) compared with all the other groups. However, beta2-microglobulin levels did not differ significantly between healthy postmenopausal women (n = 38) and patient's with Paget's bone disease (n = 40)(P = 0.5095), or between women with postmenopausal osteoporosis (n = 30) and women with hyperthyroidism (n = 20)(P = 0.7890). TRAP concentrations differed significantly in all the groups paired except for women with Paget's bone disease and women with either hyperparathyroidism or hyperthyroidism (P = 0.5179 and 0.6993, respectively); likewise, TRAP levels did not differ significantly between the women with hyperparathyroidism and those with hypothyroidism (P = 0.7804). After calcitonin treatment, there was a 22% increase in beta2-microglobulin, a 17% decrease in TRAP, and a 39% decrease in alkaline phosphatase, all of which were significant at P < 0.0001. Our findings indicate that serum beta2-microglobulin, like osteocalcin, behaves as a biological marker of remodeling in a number of diseases with enhanced bone remodeling but not in Paget's bone disease.

Acid Phosphatase↗

PubMed1995

Thromboxane A2 and platelet-activating factor decrease in the platelet-mesangial cell interactions.

To analyze the metabolisms of platelet-activating factor (PAF) and Thromboxane A2 (TxA2) when platelets and mesangial cells (MC) interact, immunoreactive thromboxane B2 (TxB2) and PAF were measured after incubation of cultured rat MC with platelets (P) and with platelet supernatants (PS). In both cases, TxB2 significantly decreased with respect to the P synthesis and to the PS content, suggesting an increased degradation of this metabolite or even the existence of a specific effect of MC upon platelet TxB2. When immunoreactive PAF was measured, results were comparable to those observed for TxB2. Moreover, when intrinsic mesangial cell synthesis of PAF was assessed by analyzing the [3H]-acetate incorporation by prelabeled MC in the HPLC fraction coeluting with cold PAF standards, it was possible to demonstrate that P or PS did not modify PAF synthesis in these cells. In summary, present results support the existence of a specific effect of mesangial cells upon platelet TxA2 and PAF.

Animals↗

PubMed1995

Zinc, biochemical markers of nutrition, and type I osteoporosis.

Having observed previously that the reduction of levels of biological markers of nutrition in postmenopausal osteoporosis may be related to zinc deficiency, we measured plasma and urinary zinc concentrations in 30 women with postmenopausal osteoporosis and in 30 healthy postmenopausal women who served as controls. Plasma zinc levels did not differ between groups, but urinary zinc excretion was significantly higher in the women with postmenopausal osteoporosis (p = 0.002). The relation between total body bone mineral content corrected for body weight (TBBMC/W) and markers of nutrition was significant (multiple regression analysis: p < 0.0001) in the women with postmenopausal osteoporosis but not in the healthy postmenopausal controls. Likewise, the relation between TBBMC/W and plasma and urinary zinc levels also was significant in the women with postmenopausal osteoporosis but not in the controls (multiple regression analysis: p = 0.0022). Neither group showed any correlation between plasma or urinary zinc concentrations and levels of biological markers of nutrition. Urinary zinc concentration correlated significantly with serum tartrate-resistant acid phosphatase level (simple linear regression analysis: r = 0.583, p < 0.001) in the women with postmenopausal osteoporosis but not in controls. TBBMC correlated with urinary zinc concentration significantly in the women with postmenopausal osteoporosis (simple linear regression: r = 0.567, p = 0.0015), but the correlation was nonsignificant in healthy postmenopausal controls. These findings indicate that the elevation of urinary zinc elimination in osteoporosis is dependent on bone resorption.

Aged↗

PubMed1995

Biochemical markers of nutrition in type-I and type-II osteoporosis.

We studied nutritional deficits, using as markers the levels of transferrin, retinol-binding protein, and prealbumin, in 20 women with osteoporotic hip fractures (type II), 40 women with vertebral fractures (type I), and two groups of age-matched control subjects. The concentrations of all three nutritional markers were lower in the two groups of patients than in their matched controls, and in type-I as compared with type-II osteoporosis. In the osteoporotic patients, simple linear regression showed a significant correlation between the variables which we studied (r2 ranged from 0.5 to 0.7; p < 0.001), the best correlation being between prealbumin and retinol-binding protein in type-II osteoporosis. Our results suggest that there is a more marked nutritional deficit in type-II than in type-I osteoporosis.

Aged↗

PubMed1994

Influence of weight and seasonal changes on radiogrammetry and bone densitometry.

We studied the behavior of radiogrammetric and densitometric measurements in relation to season and body weight in a group of 30 healthy premenopausal women. Measurements were made at 6-month intervals, in summer/fall when bone density increases and in winter/spring when bone density declines. Total body bone mineral content (TBBMC) and regional bone mineral content (RBMC) were measured using dual-energy X-ray absorptiometry (DXA). Metacarpal radiogrammetry was carried out with computed radiography. Weight and body mass index increased significantly in winter (P < 0.05) and total body and RBMC decreased (P < 0.001). The opposite occurred in summer: weight and body mass index decreased significantly (P < 0.05) and total body and regional bone mineral content increased (P < 0.001). Differences in TBBMC persisted when the measurement was corrected for weight (TBBMC/W) (P < 0.001), but not for metacarpal cortical thickness corrected for weight. In the first measurement made there were significant relations between weight and both TBBMC (P < 0.001) and metacarpal cortical thickness (P < 0.005). The relation between weight and TBBMC remained significant in later measurements, but the relation between weight and metacarpal cortical thickness ceased to be significant in the second and fourth measurements. Our results show that there is an important seasonal variation in bone mass and that DXA is more sensitive than radiogrammetry in registering these changes.

Absorptiometry, Photon↗

PubMed1994

beta 2-Microglobulin in Paget's bone disease.

On the basis of earlier findings of increased serum beta 2-microglobulin concentration in women with postmenopausal osteoporosis, we decided to study serum beta 2-microglobulin concentration in other bone diseases. In 28 patients with untreated Paget's bone disease, serum beta 2-microglobulin concentration was normal (1.49 +/- 0.41 mg/liter versus 1.36 +/- 0.21 mg/liter in 42 control subjects, P = ns), a finding that contradicts reports in the literature. We found that serum beta 2-microglobulin concentration was related negatively and significantly (r2 = -0.154, P = 0.0354) with serum total alkaline phosphatase concentration, but not with serum tartrate-resistant acid phosphatase concentration (p = ns). Urinary elimination of beta 2-microglobulin was lower in the patients with Paget's disease than in the controls (34 +/- 28 versus 120 +/- 21 mg/liter, P < 0.001). These findings suggest that beta 2-microglobulin behaves similarly to osteocalcin (BGP) in Paget's bone disease and that its concentration remains within normal levels perhaps because of the rate of reuptake of beta 2-microglobulin in bone neoformation.

Acid Phosphatase↗

PubMed1994

Longitudinal study of the effect of calcium pidolate on bone mass in eugonadal women.

Seventy-two eugonadal women, mean age 39 +/- 4 years, with a z score for total body bone mineral content (BMC) of less than -1.5 (mean -1.80 +/- 0.12) were selected from a previous screening study of normal values of total body and regional BMC in women using dual-energy X-ray absorptiometry. The women were distributed into two groups: 36 women undergoing treatment with 1 g/day of elemental calcium in the form of calcium pidolate and 36 women not treated. One year later, total body BMC, regional BMC in arms, legs and trunk, 24-hour urinary calcium excretion (Ca 24 hour), fasting urinary calcium/creatinine ratio, and serum tartrate-resistant acid phosphatase concentration were measured in both groups. There was a significant increase in total body and regional BMC (P < 0.001) in the group taking calcium pidolate. The increase was greater in arms and legs (2.5%) than in trunk (1.7%), being 2.6% for total body BMC. The z score increased from -1.81 +/- 0.13 to -1.52 +/- 0.12 (16%, P < 0.001). The corporal index did not change, and total body BMC corrected for fat-free body mass increased by 6.7% (P < 0.001). These changes were accompanied by an increase in 24-hour urinary calcium excretion and a decrease in urinary calcium/creatinine ratio and serum tartrate-resistant acid phosphatase concentration (P < 0.05 for all). There was a correlation between cumulative calcium dose at the end of treatment and gain in total body BMC (r2 = 0.925, P < 0.001). The untreated group showed no changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

PubMed1994

Total and regional bone mineral content in primary hyperparathyroidism: sex differences.

Changes in cortical and trabecular bone mass occurring in primary hyperparathyroidism are the subject of controversy. We measured the total and regional bone mass in a group of patients and controls and analyzed the observed changes with respect to sex and other characteristics. Parathormone, serum calcium, serum phosphorus, tubular resorption of phosphates, alkaline phosphatase, and tartrate-resistant acid phosphatase differed significantly (p < 0.001 for all) between patients and controls. All the patients had significantly less total and regional bone mass; the regional bone mass of the arms did not differ. When analyzed according to sex, we found that women had a significant reduction in bone mass in all the zones studied (p < 0.001), whereas men had a significant decrease in bone mass only in the head (p < 0.025). Our findings show that hyperparathyroidism is accompanied by a loss of bone mass except in the arms, and that predominantly both cortical bone (legs, pelvis and skull) and trabecular bone (trunk) are affected. This means that the skeleton suffers generalized bone loss and a significant reduction in total body calcium content. Although we did not study many men, their bone involvement was less intense, and there was a clear difference between the sexes in this respect.

Aged↗

PubMed1993

Biochemical markers of nutrition in osteoporosis.

Thirty-six women with vertebral osteoporosis showed significantly decreased levels of biochemical markers of nutrition, transferrin (P < 0.001), prealbumin (P < 0.001), retinol binding-protein (P < 0.001), and fibronectin (P < 0.001), compared with 40 healthy women of similar age. Multiple regression analysis showed a significant (R2 = 0.509; P = 0.0068) correlation between bone mineral content and biochemical markers of nutrition in the osteoporotic patients but not in the control group. These data suggest that postmenopausal osteoporosis may be associated with a nutritional deficiency.

Aged↗

PubMed1993

Total and regional bone mineral content in women treated with GnRH agonists.

Changes in bone mineral content induced by GnRH agonists were investigated by measuring total body bone mineral content (TBBM) and regional bone mineral content (BMC) (arms, legs, trunk, pelvis) and densities with dual energy X-ray absorptiometry in 25 premenopausal women before and after a 6-month treatment with gonadotropin-releasing hormone (GnRH) agonists. Biological markers of bone remodeling, estrogens, luteinizing hormone, and follicle-stimulating hormone were also measured. Weight and body mass index increased significantly after treatment (P < 0.05), and TBBM, corrected for weight (TBBM/W), decreased (P < 0.001). The changes in BMC that we observed ranged from +2.5% to -6.9%. The greatest decrease in regional BMC occurred in the trunk (4.4%, P < 0.001), with TBBM decreasing by 2.1% (P < 0.001). No significant changes were observed in the limbs. Tartrate-resistant acid phosphatase (TRAP) increased significantly after treatment (P < 0.001) and a significant negative correlation between TRAP and TBBM (P < 0.001) and between TRAP and estradiol (P < 0.001) were observed before treatment. The lack of changes observed in the BMC of the limbs indicate that GnRH agonists cause a preferential loss of BMC in trunk osseous structures, a situation similar to that of the first years of menopause.

Absorptiometry, Photon↗

PubMed1993

Direct interactions between platelets and cultured rat mesangial cells.

Platelets seem to be involved in the pathogenesis of some kidney diseases, but the exact relationships between platelets and the changes in renal function are incompletely known. Mesangial cells (MC) were incubated with platelet-supernatants (PS) and cellular surface area (CSA) and myosin light-chain phosphorylation (MLCP) were measured. CSA of PS-incubated MC (PS-MC) significantly diminished, as compared to control MC (70 +/- 6% vs. 100 +/- 5%). PS induced a significant increase in MLCP with respect to control cells (150 +/- 23% vs. 100 +/- 18%). When platelets were pretreated with indomethacin, the PS-dependent contraction was abolished. Pretreatment with sulotroban (SU) or BN-52021 (BN), a thromboxane A2 (TXA2) and a platelet-activating factor (PAF) receptor blocker respectively, also completely blocked the PS effects. In other experiments, platelets were activated with thrombin (T), adding the so obtained PS to MC. Moreover, cells were also preincubated with T and then added PS. No changes in CSA were observed in either case. It may be concluded that PS contracted cultured MC, and these changes could be related to the decreased glomerular filtration rate (GFR) observed in some diseases in which platelets seem to be involved. TXA2 and PAF may be responsible for this effect. In contrast, T incubation inhibited the effect of PS, perhaps through a direct relaxing effect of T in MC.

Animals↗

PubMed1993

Changes in renal function in acute experimental pancreatitis in rats: a therapeutic role for somatostatin.

1. The present study was designed to determine the changes in renal function in two models of experimental pancreatitis in rats, in an attempt to assess the possible pathogenic role of reactive oxygen species and to elucidate a possible therapeutic role for somatostatin. 2. Mild pancreatitis was induced by low blockade of the biliary duct and severe pancreatitis was evoked by retrograde infusion of bile salts. Renal function was studied by clearance techniques in rats with pancreatitis, treated or not treated with somatostatin. Plasma and glomerular malonyldialdehyde levels were measured by the thiobarbituric acid method. 3. Renal function did not change in rats with low blockade of the biliary duct, but animals receiving a retrograde infusion of bile salts showed a significant decrease in glomerular filtration rate and renal plasma flow with respect to sham-operated animals. 4. Plasma malonyldialdehyde levels increased significantly in rats treated with bile salts with respect to control animals, whereas no changes were detected in glomerular malonyldialdehyde levels. Thus, the renal dysfunction does not seem to be related to an increased production of reactive oxygen metabolites at the glomerular level. 5. Somatostatin infusion significantly improved renal function in rats with severe pancreatitis (retrograde infusion of bile salts) by increasing glomerular filtration rate, renal plasma flow and filtration fraction. These results support a possible therapeutic role for somatostatin in the renal dysfunction associated with the severe forms of pancreatitis.

Acute Disease↗

PubMed1993

A longitudinal study of total and regional bone mineral content and biochemical markers of bone resorption in patients with idiopathic hypercalciuria on thiazide treatment.

The effect of thiazides on total body bone mineral content and axial (trunk) and peripheral (arms) bone mass was evaluated. First, dual-energy X-ray absorptiometry was used to study bone mass in 24 patients with idiopathic hypercalciuria and in 22 healthy subjects. Next, the patients were randomized into a group of 14 patients treated with chlorthalidone (50 mg/day) and a group of 10 untreated patients who served as controls; in these two groups biochemical and bone mass studies were repeated 1 year later. Compared with healthy controls, patients with idiopathic hypercalciuria had less bone mass in total body (p < 0.02), arms (p < 0.001), and trunk (p < 0.05). After 1 year, the group of patients treated with thiazides manifested an increase of bone mass in total body (p < 0.0045), arms, and trunk (p < 0.0001) and a decrease in 24-hour calciuria, urinary calcium/creatinine ratio, and serum tartrate resistant acid phosphatase concentration; the untreated group of patients lost bone mass in all three sites. Under baseline conditions, the groups of treated and untreated patients exhibited a negative linear regression between total body bone mass and both urinary calcium/creatinine (r2 = 0.234; p < 0.001) and serum tartrate resistant acid phosphatase concentration (r2 = 0.399; p < 0.0001). Our results confirm the favorable effect of thiazides on bone mass and provide evidence of enhanced bone remodeling in idiopathic hypercalciuria.

Absorptiometry, Photon↗

PubMed1993

Total and regional bone mass values and biochemical markers of bone remodeling in endometriosis.

OBJECTIVE: TO measure peripheral, axial, and total bone mass and to assess markers of bone remodeling in women with endometriosis, with the aim of addressing previous reports of diminished peripheral bone mass in these patients. METHODS: Whole body bone densitometry, estradiol (E2) levels, and biochemical bone markers (calcium, phosphorus, total alkaline phosphatase, tartrate-resistant acid phosphatase, and total proteins) were determined in 28 patients with endometriosis and compared with findings in 33 controls. RESULTS: There were no significant differences between the groups in bone mass at different sites or in biochemical bone markers. We observed a significant negative correlation between tartrate-resistant acid phosphatase and E2 levels (P < .001) and with total (P < .001), head (P < .01), and axial (trunk) (P < .001) bone mass. Total alkaline phosphatase did not correlate with any of the indices studied. CONCLUSIONS: Bone mass was not lower in any of the areas studied in women with endometriosis. There was a significant negative correlation of tartrate-resistant acid phosphatase with E2 and with total, head, and trunk bone mass.

Absorptiometry, Photon↗

PubMed1992

Effects of reactive oxygen species on cultured rat mesangial cells and isolated rat glomeruli.

The effects of reactive oxygen species (ROS) on cultured rat mesangial cells were studied by measuring planar cell surface area (PCSA) after incubation with xanthine plus xanthine oxidase (XXO), in the presence of superoxide dismutase (SOD; 5 micrograms/ml) or catalase (CAT; 20 micrograms/ml), or after incubation with H2O2. Myosin light chain (MLC) phosphorylation was assessed in cells prelabeled with o-[32P]phosphoric acid and incubated with H2O2, after protein separation with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A possible intermediate role for platelet-activating factor (PAF) was analyzed by preincubation of the cells with a PAF antagonist BN 52021 (BN, 5 x 10(-5) M) and by measuring PAF-specific [3H]acetate incorporation and immunoassayable PAF. XXO significantly decreased PCSA (14%), an effect abolished by CAT but not by SOD. H2O2 induced a similar effect, in a dose-dependent and time-dependent manner. MLC phosphorylation increased by 81 +/- 15% after H2O2 incubation, and this effect was blocked by BN. BN also completely blocked the effect of H2O2 on PCSA. PAF-specific [3H]acetate incorporation increased in the presence of H2O2 (from 6,886 +/- 2,030 to 58,703 +/- 16,063 counts.min-1.mg-1) as well as the immunoassayable PAF production by cells (from 0.90 +/- 0.19 to 6.71 +/- 2.27 ng/mg). These results suggest that ROS, particularly H2O2, could modulate the surface area of mesangial cells, modifying the ultrafiltration coefficient, thus explaining the decrease in glomerular filtration rate in those pathological situations characterized by an increased ROS synthesis. PAF could be involved in the genesis of these effects.

Animals↗

PubMed1991

Total body bone mineral and tartrate-resistant acid phosphatase levels in type I and III osteogenesis imperfecta.

Serum tartrate-resistant acid phosphatase (TRAP) and total body bone mineral content (TBBM) were determined in a group of 16 children with osteogenesis imperfecta (OI) aged 5-14 years, 9 of whom suffered from type I and 7 from type III OI. TRAP and TBBM were also determined in a group of 26 normal children of a similar age range. TRAP levels were reduced in the type I and III OI groups (p less than 0.001). TBBM levels were lower in type I OI than in type III (p less than 0.005), and both OI groups showed reduced levels compared to the controls (p less than 0.001). The control group subjects showed a significant correlation between TRAP and TBBM (r = -0.62; p less than 0.001) which was not observed in the OI groups. Since TRAP is a biological marker of bone turnover, the results suggest that bone turnover is reduced in OI.

Absorptiometry, Photon↗