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Biomedical subjects

A Jara

Publications and source records attributed to A Jara.

At least 37 records · Page 2Linked to original sources
PubMed1999

Dynamics of skeletal resistance to parathyroid hormone in the rat: effect of renal failure and dietary phosphorus.

UNLABELLED: Secondary hyperparathyroidism develops in renal failure and is generally ascribed to factors directly affecting parathyroid hormone (PTH) production and/or secretion. These include hypocalcemia, phosphorus retention, and a calcitriol deficiency. However, not often emphasized is that skeletal resistance to PTH is an important factor. Our study evaluated: (1) the relative effects of uremia and dietary phosphorus on the skeletal resistance to PTH; and (2) how, during a PTH infusion, the dynamics of skeletal resistance to PTH were affected by renal failure. Renal failure was surgically induced and, based on serum creatinine, rats were divided into normal, moderate renal failure, and advanced renal failure. In each group, three diets with the same calcium (0.6%) but different phosphorus contents were used: high (1.2%, HPD); moderate (0.6%, MPD); and low (0.2%, LPD) phosphorus. The study diet was given for 14-16 days followed by a 48 h infusion of rat PTH(1-34) (0.11 microg/100 g per hour), a dose five times greater than the normal replacement dose. During the PTH infusion, rats received a calcium-free, low phosphorus (0.2%) diet. In both moderate and advanced renal failure, the PTH level was greatest in the HPD group (p < 0.05) and, despite normal serum calcium values, PTH was greater in the MPD than the LPD group (p < 0.05). Despite phosphorus restriction and normal serum calcium and calcitriol levels in the azotemic LPD groups, the PTH level was greater (p < 0.05) in the LPD group with advanced rather than moderate renal failure. During PTH infusion, the increase in serum calcium was progressively less (p < 0.05) in all groups as renal function declined. Furthermore, despite normal and similar serum phosphorus values at the end of PTH infusion, the serum calcium concentration was less (p < 0.05) in the HPD group than the other two groups and similar in the LPD and MPD groups. IN CONCLUSION: (1) uremia and phosphorus each had separate and major effects on skeletal resistance to PTH; (2) skeletal resistance to PTH was an important cause of secondary hyperparathyroidism, even in moderate renal failure; (3) during PTH infusion, the dynamics of skeletal resistance to PTH changed because all groups received a low phosphorus diet, and the adaptation to a new steady state was delayed by the degree of renal failure and the previous dietary phosphorus burden; and (4) normal serum phosphorus may not be indicative of body phosphorus stores during states of disequilibrium.

Adaptation, Physiological↗
PubMed1999

Phosphate depletion in the rat: effect of bisphosphonates and the calcemic response to PTH.

BACKGROUND: The removal of phosphate from the diet of the growing rat rapidly produces hypercalcemia, hypophosphatemia, hypercalciuria, and hypophosphaturia. Increased calcium efflux from bone has been shown to be the important cause of the hypercalcemia and hypercalciuria. It has been proposed that the increased calcium efflux from bone is osteoclast mediated. Because bisphosphonates have been shown to inhibit osteoclast-mediated bone resorption, this study was performed to determine whether bisphosphonate-induced inhibition of osteoclast function changed the biochemical and bone effects induced by phosphate depletion. METHODS: Four groups of pair-fed rats were studied: (a) low-phosphate diet (LPD; phosphate less than 0.05%), (b) LPD plus the administration of the bisphosphonate Pamidronate (APD; LPD + APD), (c) normal diet (ND, 0.6% phosphate), and (d) ND + APD. All diets contained 0.6% calcium. A high dose of APD was administered subcutaneously (0.8 mg/kg) two days before the start of the study diet and on days 2, 6, and 9 during the 11 days of the study diet. On day 10, a 24-hour urine was collected, and on day 11, rats were either sacrificed or received an additional APD dose before a 48-hour parathyroid hormone (PTH) infusion (0.066 microgram/100 g/hr) via a subcutaneously implanted miniosmotic pump. RESULTS: Serum and urinary calcium were greater in the LPD and LPD + APD groups than in the ND and ND + APD groups [serum, 11.12 +/- 0.34 and 11.57 +/- 0.45 vs. 9.49 +/- 0.17 and 9.48 +/- 0.15 mg/dl (mean +/- SE), P < 0.05; and urine, 8.78 +/- 2.74 and 16.30 +/- 4.68 vs. 0.32 +/- 0.09 and 0.67 +/- 0.28 mg/24 hr, P < 0.05]. Serum PTH and serum and urinary phosphorus were less in the LPD and LPD + APD than in the ND and ND + APD groups (P < 0.05). The calcemic response to PTH was less (P < 0.05) in the LPD and LPD + APD groups than in the ND group and was less (P = 0.05) in the LPD + APD than in the ND + APD group. Bone histology showed that phosphate depletion increased the osteoblast and osteoclast surface, and treatment with APD reduced the osteoblast surface (LPD vs. LPD + APD, 38 +/- 4 vs. 4 +/- 2%, P < 0.05, and ND vs. ND + APD, 20 +/- 2 vs. 5 +/- 2%, P < 0.05) and markedly altered osteoclast morphology by inducing cytoplasmic vacuoles. CONCLUSIONS: (a) Phosphate depletion induced hypercalcemia and hypercalciuria that were not reduced by APD administration. (b) The calcemic response to PTH was reduced in phosphate-depleted rats and was unaffected by APD administration in normal and phosphate-depleted rats, and (c) APD administration markedly changed bone histology without affecting the biochemical changes induced by phosphate depletion.

Animals↗
PubMed1996

The set point of calcium and the reduction of parathyroid hormone in hemodialysis patients.

Since in some studies in hemodialysis patients calcitriol treatment has resulted in a reduction of both parathyroid hormone (PTH) levels and the set point of calcium, it has been suggested that that the set point of calcium reflects a reduction in the magnitude of hyperparathyroidism. However, others have maintained that the set point of calcium is primarily an indicator of the serum calcium at which PTH is secreted and may be dissociated form the magnitude of hyperparathyroidism. The present study was designed to evaluate how a reduction in PTH levels associated with an increase in the predialysis (basal) serum calcium would affect the set point of calcium. Two different treatments were used to produce a reduction in PTH that was associated with an increase in predialysis serum calcium. In the first group, hemodialysis patients received 2 micrograms of intravenous calcitriol and were dialyzed with a 3.5 mEq/liter calcium dialysate for six weeks; in the second group, hemodialysis patients were dialyzed with a 4 mEq/liter calcium dialysate and had oral calcium supplementation increased for six weeks. In both groups, low and high calcium studies were performed to determine the PTH-calcium relationship before treatment, at the end of six weeks of treatment, and six weeks after the discontinuation of treatment. In the calcitriol group the predialysis calcium increased form 9.62 +/- 0.34 to 10.56 +/- 0.31 mg/dl, P < 0.05 and the set point of calcium increased from 9.34 +/- 0.23 to 9.79 +/- 0.25 mg/dl, P < 0.05 at the same time as maximally stimulated PTH decreased from 2637 +/- 687 to 1555 +/- 617 pg/ml, P < 0.05. In the high calcium dialysate group, the predialysis serum calcium increased from 9.19 +/- 0.31 to 9.84 +/- 0.28 mg/dl, P < 0.05, and set point of calcium increased form 9.01 +/- 0.28 to 9.39 +/- 0.22 mg/dl, P < 0.05 at the same time as maximally stimulated PTH decreased from 1642 +/- 450 to 1349 +/- 513 pg/ml, P < 0.05. Discontinuation of treatment for six weeks resulted in a return to pretreatment values. In conclusion, our results would suggest that (1) the set point of calcium may not be a reliable indicator of the magnitude of hyperparathyroidism during calcitriol treatment, and (2) PTH secretion may adapt to the ambient serum calcium concentration.

Adult↗
PubMed1995

Development of secondary hyperparathyroidism and bone disease in diabetic rats with renal failure.

Renal osteodystrophy in diabetic patients on maintenance hemodialysis is characterized by a higher prevalence of low bone turnover and is associated with a relative deficiency of parathyroid hormone (PTH) as compared with non-diabetic hemodialysis patients. The goal of the study was to evaluate how diabetes affected the development of secondary hyperparathyroidism (2 degrees HPT) and bone disease in azotemic rats. Three groups of 5/6 nephrectomized, pair-fed male Wistar rats maintained on a high phosphorus (1.2%) diet were studied: (1) the control group, non-diabetic azotemic rats (NDR); and two streptozotocin-induced diabetic azotemic groups, (2) poorly-controlled diabetic rats (PCDR) which received only enough NPH insulin to maintain the blood glucose between 300 and 400 mg/dl, and (3) well-controlled insulin-treated diabetic rats (IDR) which received a continuous insulin infusion for 14 days via a subcutaneously implanted miniosmotic pump. Serum calcium, phosphorus and creatinine levels were similar among the three groups. Blood glucose levels were greater in the PCDR group than the IDR and NDR groups (358 +/- 11 vs. 83 +/- 9 and 87 +/- 8 mg/dl, respectively; P < 0.001). Rats in the PCDR group weighed less at sacrifice as compared with the IDR and NDR groups (P < 0.05). Serum PTH levels (normal 47 +/- 2 pg/ml) were elevated, but not different among the three groups (136 +/- 34, 147 +/- 21 and 98 +/- 8 pg/ml in the PDCR, IDR and NDR groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Studies in a hemodialysis patient indicating that calcitriol may have a direct suppressive effect on bone.

Calcitriol putatively suppresses bone activity by decreasing parathyroid hormone (PTH) levels. Results of studies in a 52-year-old female maintenance hemodialysis patient suggest that calcitriol may also have a direct suppressive effect on bone. The PTH-calcium relationship was evaluated through the use of low (1 mEq/l) and high (4 mEq/l) calcium hemodialyses that were performed before the initiation of calcitriol treatment, at the end of 6 weeks of thrice-weekly intravenous calcitriol administration, and 6 weeks after the discontinuation of calcitriol. During the low-calcium dialysis, serum calcium decreased more rapidly and to a greater magnitude after calcitriol treatment despite no appreciable difference in basal and maximally stimulated PTH levels; during the high-calcium dialysis, calcitriol treatment resulted in a more rapid increase in serum calcium despite no appreciable difference in basal and maximally suppressed PTH levels. Discontinuation of calcitriol resulted in responses to the low and high calcium dialyses that were similar to those observed before calcitriol treatment. In conclusion, the results suggest that calcitriol may have a direct suppressive effect on bone that is independent of PTH.

Alkaline Phosphatase↗
PubMed1995

Urinary cyclic adenosine 3',5'-monophosphate response in McCune-Albright syndrome: clinical evidence for altered renal adenylate cyclase activity.

The recent finding of an activating mutation in the Gs alpha protein, the protein that couples receptors to stimulation of adenylate cyclase, from endocrine and nonendocrine tissues of patients with McCune-Albright syndrome (MAS) suggests that alterations in adenylate cyclase activity may account for the clinical abnormalities in these patients. Many patients with MAS have hypophosphatemia. This may result from the presence of the activating Gs alpha mutation in proximal renal tubules or the elaboration of a phosphaturic factor from fibrous dysplasia. We, therefore, sought to characterize renal cAMP generation and phosphate handling in MAS patients. Intravenous infusion of PTH is a classic clinical test used to evaluate hormonal responsiveness of renal proximal tubule adenylate cyclase and examine PTH-dependent phosphate clearance. We performed PTH infusion in 6 MAS patients, 10 normal subjects, and 6 patients with pseudohypoparathyroidism (PHP). The basal urinary cAMP (UcAMP) level in the MAS group [5.5 +/- 2.6 nmol/dL glomerular filtration (GF)] was elevated (P < 0.05) compared to those in both normal subjects (3.2 +/- 1.2 nmol/dL GF) and patients with PHP (1.9 +/- 0.6 nmol/dL GF). However, PTH-stimulated peak UcAMP (15.0 +/- 7.0 nmol/dL GF) and the peak/basal UcAMP ratio (3.1 +/- 1.7) in MAS were significantly lower than the respective values in normal subjects (30.8 +/- 16.9 nmol/dL GF and 9.3 +/- 2.9; P < 0.05 for both) and were statistically similar to the blunted levels in PHP (respectively, 3.1 +/- 1.5 nmol/dL GF and 2.0 +/- 1.7). By contrast, the PTH-induced phosphaturic response in MAS patients was similar to that in the normal subjects. Our study provides clinical evidence that MAS patients have altered renal adenylate cyclase activity, manifested by an elevated basal UcAMP, but a blunted UcAMP response to PTH stimulation. These observations are presumably due to a mutation in the Gs alpha protein in the renal tubules. Despite the blunted UcAMP excretion, the phosphaturic response to PTH in MAS patients is intact.

Adenylyl Cyclases↗
PubMed1995

Differences in the dynamics of parathyroid hormone secretion in hemodialysis patients with marked secondary hyperparathyroidism.

Hemodialysis patients with predialysis intact parathyroid hormone (PTH) levels of more than 500 pg/mL are generally considered to have marked secondary hyperparathyroidism. Because the serum calcium level in these patients varies from low to high, it is not clear whether every hemodialysis patient with a PTH level > 500 pg/mL is part of a uniform group. The dynamics of PTH secretion in 21 hemodialysis patients with predialysis (basal) intact PTH levels > 500 pg/mL (range, 506 to 1978 pg/mL) has been evaluated. The basal/maximal PTH ratio, an indicator of the degree of relative PTH stimulation in the baseline state, was inversely correlated with the maximal PTH (r = -0.71), the basal serum calcium (r = -0.70), and the difference between the serum calcium at basal and maximal PTH (r = 0.81); the latter is the decrement in serum calcium from baseline necessary to maximally stimulate PTH. Because the basal PTH level appeared to be disproportionately influenced by hypocalcemia, the 21 patients were separated into two groups on the basis of the basal serum calcium (Group I < 9 mg/dL and Group II > 9 mg/dL). Basal PTH was not different between the two groups, even though maximally stimulated PTH (1,219 +/- 204 versus 2,739 +/- 412 pg/mL; P < 0.01) as induced by hypocalcemia and maximally suppressed PTH (217 +/- 37 versus 528 +/- 104; P = 0.05) as induced by hypercalcemia were less in Group I with the low basal calcium; moreover, the ratio of basal/maximal PTH was higher (73 +/- 6 versus 47 +/- 5%; P < 0.01) in Group I with the low basal calcium. These results suggest that the reason for a basal PTH > 500 pg/mL may be different among hemodialysis patients. In hypocalcemic patients, the low serum calcium appeared to be a major impetus for the high basal PTH level. In conclusion, (1) the maximally stimulated PTH appears to provide a better means of separating patients with marked secondary hyperparathyroidism than the basal PTH and (2) hemodialysis patients with basal PTH levels > 500 pg/mL may not be a uniform group.

Adult↗
PubMed1995

Sensitivity of antigen ELISA test for detecting Trypanosoma evansi antigen in horses in the subtropical area of Argentina.

The sensitivity of an antigen detection enzyme immunoassay (Ag-ELISA) based on a Trypanosoma brucei group-specific monoclonal antibody was evaluated to detect circulating Trypanosoma evansi antigen in horse sera. Three horses and 2 mules were experimentally infected with T. evansi. Circulating antigens were detected on 7 and 21 days postinfection. Antigen levels increased during the course of the illness and remained high even when parasitemia was low or when parasites could not be detected. Antigens were cleared from serum when drug treatment was effective but persisted when it was not. In 6 outbreaks of "mal de caderas" involving 125 horses, T. evansi was found in 78 horses using standard parasite detection methods and antigenemia was detected in 58 of them (74%). The Ag-ELISA sensitivity rate varied between 63% and 100% for the 6 different outbreaks. A combination of Ag-ELISA and parasitologic methods diagnosed a total of 93 infected animals. These results show that the Ag-ELISA test is useful both to diagnose T. evansi and to assess the efficacy of drug treatment in horses.

Animals↗
PubMed1994

Comparison of two parathyroid hormone assays for the rat: the new immunoradiometric and the older competitive binding assay.

A competitive binding assay for parathyroid hormone (PTH INS) has been used since 1986 to measure PTH in rats. During the past year an immunoradiometric assay for the measurement of PTH (PTH IRMA) in the rat was developed. The purpose of the present study was to compare results obtained with the PTH INS and IRMA and to provide a framework for comparison for investigators who have used the PTH INS in previous studies. A total of 99 rats were studied; 27 rats had normal renal function, and 72 rats had surgically induced renal failure. In the azotemic rats, the magnitude of hyperparathyroidism was varied by changing the calcium and phosphorus composition of the diet. The correlation between the two PTH assays in the 99 rats was r = 0.98, p < 0.001. For the 27 rats with normal renal function, the correlation even within the narrow range of normal PTH values was significant, r = 0.71, p < 0.001. In the 72 azotemic rats, in which the highest INS PTH value was approximately 17 times normal, the correlation between the two PTH assays was r = 0.98, p < 0.001. The PTH IRMA provides distinct advantages, such as extended standard range, shortened incubation time, increased sensitivity, and technical simplicity, but our results indicate that the PTH INS provided an accurate measurement of PTH. Furthermore, our results should provide investigators who have used the PTH INS in previous studies with a framework for comparison with studies in which the PTH IRMA was used.

Animals↗
PubMed1994

Bone density and turnover in Addison's disease: effect of glucocorticoid treatment.

Osteoporosis is a well-known side-effect of chronic treatment with glucocorticoids. We have studied vertebral bone mineral density (BMD) and biochemical markers of bone metabolism in 30 patients diagnosed of Addison's disease (AD) to determine the effect of long-term replacement treatment with hydrocortisone (30 mg/day) or prednisone (7.5 mg/day). Lumbar bone mineral density was measured with dual energy X-ray absorptiometry in L-1-4 in two occasions, separated by 12 months. BMD in premenopausal women and men with AD was similar to healthy controls and postmenopausal women had slightly lower results. Rate of change of bone density followed up over a period of 12 months was -0.82%. Bone loss was not influenced by duration or type of steroid treatment. Biochemical parameters, serum calcium, alkaline phosphatase, osteocalcin, procollagen type I, PTH and 25(OH)vitamin D were within normal limits. Our results show that in patients with AD, after replacement with low doses of glucocorticoids there is no significative trabecular bone loss neither modifications in bone formation markers.

Absorptiometry, Photon↗
PubMed1994

Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat.

Secondary hyperparathyroidism (2 degree HPT) develops as a result of renal failure. Hypocalcemia, phosphorus retention, calcitriol deficiency and skeletal resistance to the calcemic action of parathyroid hormone (PTH) are closely interrelated pathogenic factors important for the development of 2 degrees HPT in renal failure. Since previous studies have mainly focused on advanced renal failure, only limited data are available in early renal failure. The goal of the present study was to evaluate how alterations in the dietary calcium and phosphorus composition affect the factors known to contribute to the genesis of 2 degrees HPT in early and more advanced renal failure. To achieve this goal, graded differences in renal function were surgically induced in 453 rats while the dietary content of calcium and phosphorus was varied. Three different diets were used: (1) a high phosphorus diet (HPD), to induce phosphorus retention and stimulate 2 degrees HPT; (2) a high calcium diet (HCaD), to inhibit calcitriol synthesis; and (3) a moderate calcium-moderate phosphorus diet (MCaPD), to separate the effects of high dietary phosphorus and calcium. Based on the serum creatinine (SCr) concentration rats were assigned to one of four different groups: (1) normal renal function (SCr < or = 0.3 mg/dl); (2) mild renal failure (SCr 0.4 to 0.6 mg/dl); (3) moderate renal failure (SCr 0.7 to 0.8 mg/dl); or (4) advanced renal failure (SCr > or = 0.9 mg/dl). As the severity of renal failure increased, progressive 2 degrees HPT developed in each of the dietary groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The calcemic response to PTH in the rat: effect of elevated PTH levels and uremia.

Secondary hyperparathyroidism (2 degrees HPT) is a consistent finding in renal failure. A decreased calcemic response (CR) to parathyroid hormone (PTH) contributes to the development of 2 degrees HPT. Since parathyroidectomy (PTX) corrects the decreased CR to PTH in azotemic animals, down-regulation of PTH receptors induced by an elevation of PTH has been advanced as an important factor in the development of 2 degrees HPT. The goal of the study was to determine in azotemic rats whether a progressive reduction of PTH improves the CR to PTH and whether the maintenance of normal PTH levels corrects the CR to PTH. Seven groups of pair-fed rats were studied. Three groups of rats had normal renal function (NRF groups) and received either a high phosphorus (HPD-NRF), a moderate phosphorus (MPD-NRF), or a low phosphorus (LPD-NRF) diet. Three azotemic (NX) groups received similar diets (HPD-NX, MPD-NX and LPD-NX groups) in order to vary the magnitude of 2 degrees HPT. A PTX was performed in a fourth azotemic group (PTX-NX) to induce the complete absence of PTH. After 14 to 16 days on the maintenance diets, the CR to PTH was determined with a 48 hour infusion of 1-34 rat PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Anemia associated with acute post streptococcal glomerulonephritis].

Thirty-three children with post-streptococcal acute glomerulonephritis, age mean: 8.3 years (range: 6 - 12) were studied prospectively. Mean initial hematocrit (Hct) was 31.6% with 90% showing Hct under the normal lower limit for this age group. Reticulocyte index (RI) was < 0.5 in half of the cases. Serum iron concentration, total iron binding capacity (TIBC) and percentage of transferrin saturation were normal for this age group although 75% of the children had increased serum ferritin levels. At the time of discharge, Hct increased to 35.1% but 44% still had anemia. Hct increased spontaneously for 105 days stabilizing at 38%. Based on Hct changes, 3 groups were defined: Group I (3 individuals): normal upon discharge; Group II (19): partial recovery at discharge, slow recovery stabilizing after 105 days; Group III (11): lower Hct, slower recovery but with RI significantly higher than group II (0.96 vs 0.45 p < 0.01). Our data suggest that although hemodilution is present in all, it may be considered the solely factor only in 3 cases (Group I). In group II, evidence of bone marrow depression was indicated by the low RI. On the other hand, the intense anemia that could not be justified only by hemodilution and marrow depression in group III, suggests other pathogenic factors.

Acute Disease↗
PubMed1994

[Bone mineralization in Chilean children determined by dual photon bone densitometry].

In 198 school age children, aged 6 to 13 years, the bone mineral density (BMD) and total bone mass (TBM) was measured in total body, lumbar spine and hip, using a double beam photon densitometer with a Gd 153 source. An increase with age of BMD and TBM was found in all the analyzed areas. At 12 years of age, TBM and BMD of total body were higher in girls than in boys. BMD of lumbar spine was significantly higher in girls than in boys at ages between 11 to 13 years. BMD of lumbar spine and femoral neck of 9 years old females were 36% and 18% respectively, lower than values of young adult Chilean females. The importance of normal values of bone mineralization for the diagnosis of bone diseases and for the evaluation of programmes directed to solve this problems is emphasized.

Absorptiometry, Photon↗
PubMed1993

[Aluminum-related bone disease in chronic hemodialysis patients].

Plasma aluminum (pAl) was measured in 58 patients coming from three centers using different preparation of dialysis water: deionizer (29 patients), softener (16 patients) and reverse osmosis (13 patients). Twenty five healthy subjects were used as controls. A deferoxamine test was performed to 11 of 19 patients with pAl between 40 and 200 micrograms/dl and a bone biopsy with double tetracycline staining was executed to 15 patients with pAl over 40 micrograms/dl. Mean pAl was 9.5 +/- 1.7 micrograms/dl in controls and 34.3 +/- 6.1 169 +/- 27.8 and 50.8 +/- 10.3 micrograms/dl in patients coming form centers using deionizers, softeners and reverse osmosis respectively. Seventy six percent of patients coming from centers using deionizers and 85% of patients coming from centers with reverse osmosis had pAl below 40 micrograms/dl and all had values below 200 micrograms/dl. Plasma aluminum had a increase of over 200 micrograms/dl in 6 of 11 patients in which the deferoxamine test was performed. Six patients had a positive staining for aluminum in bone biopsies (three with basal pAl over 200 micrograms/dl and one with a increase in pAL after deferoxamine < 200 micrograms/dl). Of these, 2 patients had a mixed osteodystrophy and 4 a low turnover bone disease. Centers with deionizers and reverse osmosis had very low aluminum levels in dialysis water and five of six patients with aluminum levels related bone disease came from the center using softener.

Aluminum↗