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Biomedical subjects

S Ljunghall

Publications and source records attributed to S Ljunghall.

At least 145 records · Page 8Linked to original sources
PubMed1993

Parathyroid hormone is able to enhance cyclic adenosine monophosphate formation without causing an increase in cytoplasmic Ca2+ in osteoblasts.

There are several reports indicating that parathyroid hormone (PTH), besides inducing the formation of cyclic adenosine monophosphate (cAMP), also causes an increase in cytoplasmic free Ca2+ ([Ca2+]i) in osteoblasts, and it has been speculated that both of these second messengers are necessary to mediate PTH-induced bone resorption. In the osteoblastic cell line MC3T3-E1, bovine PTH 1-34 (10 nmol/l-1 mumol/l) stimulated cAMP formation but did not cause an increase in [Ca2+]i in adherent single cells (basal [Ca2+]i = 151 +/- 5 nmol/l, mean +/- SEM; N = 98). In contrast, subsequent addition of bradykinin (1 mumol/l) resulted in a transient increase in [Ca2+]i from a basal level of 155 +/- 11 nmol/l to a peak value of 351 +/- 60 nmol/l (N = 14). When the PTH challenge was followed by the addition of thrombin (10 U/ml), the latter induced a transient rise in [Ca2+]i from a basal level of 173 +/- 12 nmol/l to a peak at 341 +/- 33 nmol/l (N = 20). Primary cultures of human osteoblasts were obtained from trabecular bone. These cells were also PTH-responsive in terms of cAMP formation. On the other hand, human PTH 1-34 (100 nmol/l) did not affect [Ca2+]i in the isolated human osteoblasts, while bradykinin (1 mumol/l) caused a transient increase in [Ca2+]i (from a basal value of [Ca2+]i at 154 +/- 10 nmol/l to a peak value of 757 +/- 147 nmol/l within 30 s; N = 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Bradykinin↗
PubMed1993

Parathyroid hormone and osteocalcin levels in plasma and ultrafiltrate during hemofiltration.

The effects of hemofiltration (HF) on serum levels of intact parathyroid hormone (PTH), as well as its mid-C regional and C-terminal fragments and bone Gla-protein (bone gamma-carboxyglutamic acid, osteocalcin), were investigated in 17 patients during one session of HF. During HF there was a significant decrease in the serum concentrations of both intact PTH (p < 0.01), mid-C regional PTH (p < 0.01) and C-terminal PTH (p < 0.01) as well as in the osteocalcin concentrations (p < 0.01). There was a significant increase in serum calcium (p < 0.05) during the procedure and this increase correlated with the reduction in PTH (r = 0.56, p < 0.05). Mid-C regional PTH and osteocalcin were found in the ultrafiltrate of all patients, while intact PTH was found in the ultrafiltrate of 8 of 17 patients and C-terminal PTH was detected only in the ultrafiltrate of one patient. The data demonstrate that the permeability of HF membranes is high enough to cause filtration of both intact PTH, PTH fragments and osteocalcin. An inhibited secretion of PTH probably played a major part in reducing intact PTH in serum during HF.

Adult↗
PubMed1993

Medical and radiologic evaluation and operative treatment of primary hyperparathyroidism.

The diagnosis of primary hyperparathyroidism (HPT) relies principally on repeated measurements of total serum calcium and determination of intact parathyroid hormone. A careful patient history and routine blood chemistry will generally verify symptoms in the common patient with HPT, who should be a candidate for surgery. The operative treatment in primary HPT is efficient, with reported high success rate, minimal complications and frequent alleviation of symptoms. Nonoperative medical surveillance should preferentially be considered in elderly patients with borderline increases in serum calcium of around 2.7 mmol/L or less, who in fact constitute a major proportion of hypercalcemic individuals detected at population screening. The patients in whom an operation is deferred should lack any symptoms or complications associated with primary HPT known to benefit from surgery, and this includes the commonly encountered neurobehavioral disability. Surveillance may also occasionally be chosen for really old individuals, when expected improvement fails to justify operative risks. In keeping with the generally liberal indications for parathyroid surgery, surveillance may be time limited if the patients develop disability or display a rise in serum calcium during follow-up.

Aged↗
PubMed1993

Biochemical markers of bone metabolism in patients with fracture of the distal forearm.

Biomarkers for bone turnover have established a place in the investigation and follow-up examinations of patients with osteoporosis, but has received little attention for the possibility that the fracture itself might interfere with the interpretation of the results. In this investigation of patients with fracture of the distal forearm, biomarkers for bone formation (serum osteocalcin and alkaline phosphatases) and for resorption (urinary calcium and hydroxyproline) were determined together with serum calcium and parathyroid hormone (PTH) in longitudinal and cross-sectional studies. During 16 weeks of follow-up examinations, starting on the day of the fracture, 13 patients with Colles' fracture displayed a consistent pattern with a moderate increase in serum alkaline phosphatase and osteocalcin, whereas the indices of bone resorption appeared unaffected. There was also a significant increase in the serum calcium concentration and a reciprocal decrease in serum PTH. A cross-sectional comparison between 99 patients and controls showed elevated osteocalcin levels in the patients and an inverse relationship between these levels and bone mineral density. The findings demonstrate that fracture healing should be considered in the interpretation of biomarkers in osteoporotic patients, and that among patients with a fracture of the distal forearm, those with biochemical evidence of increased bone turnover have the lowest bone mass.

Aged↗
PubMed1993

Calcium metabolism and sodium sensitivity in hypertensive subjects.

A pattern of negative calcium balanced with lowered levels of serum ionized calcium (Ca2+) and increased urinary excretion of calcium has been reported in hypertensive men. In the present study, ten untreated hypertensive subjects were salt loaded (20 g NaCl) for one week after a week on a low salt diet (< 3 g). The change in mean blood pressure (MBP) at the end of the high compared with the low salt diet was called salt sensitivity and was related to indexes of mineral metabolism. It was found that salt sensitivity was significantly correlated with both plasma ionized calcium (Ca2+) and serum calcium concentrations (both r = 0.64, P < 0.05) on the different diets. These relationships were strongest when sodium sensitivity was measured in the standing position during the low salt intake suggesting a role for an increased sympathetic tone. Salt loading increased the urinary excretion of calcium by 95% and also induced reductions in haemoglobin, serum albumin and serum calcium (P < 0.001). Ca2+, on the other hand, remained constant after salt loading. In conclusion, low levels of plasma ionized calcium and serum calcium were mainly found in hypertensive subjects with a low sensitivity to salt. Salt loading induced an increased calciuresis, haemodilution and possibly a shift of calcium from its protein-bound to its ionized form. The findings support the view that calcium metabolism is related to the regulation of BP.

Aged↗
PubMed1992

Cellular retinoic acid-binding protein type II is expressed in adult human osteoblasts and in adult liver.

In this study we have used a reverse transcription polymerase chain reaction (RT-PCR) to demonstrate that adult primary human osteoblasts and SaOS-2, a human osteosarcoma-derived cell line with osteoblastic properties, express cellular retinol-binding protein I (CRBP I), cellular retinoic acid-binding protein II (CRABP II), and very low levels of CRABP I. We also show that CRABP II is expressed in the adult liver, which does not express CRABP I. The results suggest that CRABP II is the important isoform in the adult bone as well as in the adult liver. Since the 9-cis retinoic acid receptor (RXR) alpha previously has been shown to be expressed predominantly in the liver, CRABP II might be involved in the transport of 9-cis retinoic acid to its nuclear receptor.

Adult↗
PubMed1992

Ga3+ inhibits parathyroid hormone release without interacting with the Ca2+ receptor of the parathyroid cell.

Gallium nitrate is an antihypercalcemic agent with established actions on bone. The effects of Ga(NO3)3 on parathyroid hormone (PTH) release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP production of enzymatically dispersed parathyroid cells from bovine as well as normal and pathological human parathyroid glands have now been studied. Ga3+ at 200 microM inhibited PTH release whereas 600 microM NO3- had no effect. The inhibition was additive to that obtained by elevating extracellular Ca2+. Unlike Ca2+, Ga3+ failed to increase [Ca2+]i or reduce cAMP formation. The results indicate that Ga3+ inhibits PTH release by a mechanism other than activation of the cation receptor of the parathyroid cells. This mechanism may contribute also to inhibition by other cations.

Animals↗
PubMed1992

Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro.

UNLABELLED: Bone resorption, in vitro, is often measured as the release of prelabelled 45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 culture medium in serum-free conditions in 0.5 cm2 multiwell culture dishes. Matrix degradation after treatment with parathyroid hormone was assessed by measuring the amount of carboxyterminal telopeptide of type I collagen (ICTP) by RIA. The data on matrix degradation was compared to the release of prelabelled 45Ca from neonatal mouse calvarial bones. We found that the dose-responses for parathyroid hormone-induced release of prelabelled 45Ca and ICTP were identical. IN CONCLUSION: RIA-analysis of the ICTP-release is an easy and accurate method to measure degradation of bone-matrix, in vitro. Furthermore, the new dissection technique, described in this report, makes it easy to obtain large amounts of bone samples and thus to perform extensive experiments, e.g. dose-responses for agents that enhance bone resorption.

Animals↗
PubMed1992

Effects of parathyroid hormone on cyclic AMP-formation and cytoplasmic free Ca2+ in the osteosarcoma cell line UMR 106-01.

The effects of parathyroid hormone (PTH) on cytoplasmic free Ca2+ (Cai2+) and cAMP-formation were investigated in the rat osteosarcoma cell line UMR 106-01. In fura-2 loaded adherent single cells bPTH 1-34 (10 nM - 1 microM) induced a rapid transient increase in Cai2+ in 11% of the studied cells. In fura-2 tracings from UMR 106-01 cells in suspension, bPTH 1-34 (0.1 microM) induced a transient increase in Cai2+ in 20% of the experiments. The transient increase in Cai2+ seen in suspensions of cells was not abolished by addition of EGTA (2.5 mM) prior to challenge with PTH, suggesting that the increase in Cai2+ was derived from intracellular stores. A marked rapid increase in cAMP-formation was observed in all experiments with cells in suspension, also in the experiments where PTH did not affect Cai2+. These data show that PTH causes a release of Ca2+ from intracellular stores in a small percentage of osteosarcoma UMR 106-01 cells, and that PTH is capable of inducing an increase in cAMP-formation without affecting Cai2+ in osteoblasts.

Animals↗
PubMed1992

Women with climacteric symptoms: a target group for prevention of rapid bone loss and osteoporosis.

The relations of vasomotor symptoms to the rate of bone loss and to the response of forearm bone mineral density (BMD) to hormone replacement therapy (HRT) were analyzed in a 2-year non-randomized study. Forty peri/postmenopausal women who were given HRT for climacteric symptoms were compared with untreated control women, individually matched for age and length of time since the last menstrual period. The women who received HRT gained, on average, about 2% in BMD, while the control women lost about 6% (mean group difference 8%; 95% confidence interval (CI) 5.7-10.2). Adjustment for potential confounders did not change the results. Sweating frequency was inversely correlated with serum estradiol levels (p = 0.05). Among untreated women the rate of bone loss was higher in those who had frequent sweating initially than in those with less frequent sweating (9% vs. 4%, mean difference 4.3%; 95% CI 0.7-7.8, p = 0.023). Among women who received HRT, those who had the highest frequency of sweating initially, compared with those with a lower frequency, showed a greater gain in bone density (mean difference 4%; 95% CI 1.2-6.8, p = 0.007). In multivariate analysis adjusting for covariates, sweating frequency remained an independent determinant of change in bone density in women both with and without HRT. When sweating frequency and serum estradiol levels were compared in a multivariate analysis, only sweating frequency showed an independent association with rate of bone loss. The findings indicate that women with severe climacteric symptoms may have an excessive rate of bone loss and should therefore be considered as a special target group for prevention of osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Histological and clinical features of non-familial primary parathyroid hyperplasia.

Relations between histopathological characteristics and clinical data were retrospectively investigated in patients with sporadic primary hyperparathyroidism due to hyperplasia. The study comprised 100 patients with chief cell hyperplasia and nine with hyperplasia of the water-clear cell type operated on during the period of 1959-1989. The chief cell hyperplasia was associated with a renal stone disorder as the predominant symptom in 41 patients, psychiatric/neuromuscular manifestations in 26 patients, while 23 patients were apparently asymptomatic. The remaining ten patients had miscellaneous symptoms. Patients with renal stones were more frequently of the male sex and generally had lower serum calcium values and less marked increments in total parathyroid glandular weights than patients with other symptoms or those who were overtly asymptomatic. Two main morphological patterns, diffuse and nodular hyperplasia, were encountered in chief cell hyperplasia. Diffuse hyperplasia was usually found in moderately enlarged glands, with a less variable size and morphology. It was also more prevalent among young patients having moderate hypercalcaemia and either recurrent renal stones or neuromuscular/psychiatric symptoms. The glands affected by nodular hyperplasia were asymmetric in size with a variable cellular arrangement and a high proportion of oxyphil cells. Nodular hyperplasia was irrespective of symptoms more frequent in the elderly patients. Water-clear cell hyperplasia was not encountered during the last decade of the study and until then it was an occasional finding in patients with marked hypercalcaemia. In this histological entity the glands were greatly and asymmetrically enlarged.

Adult↗
PubMed1992

Serum urate and renal function in different forms of hypercalcemia.

In order to investigate the relationships between serum calcium, urate and kidney function, serum calcium, urate, creatinine and urea were measured at 100 occasions in hypercalcemic cancer patients together with 113 preoperative measurements in HPT subjects and 106 measurements in normocalcemic control persons. When compared to normocalcemic control subjects (serum urate 336 +/- 110 mumol/l) both HPT subjects (356 +/- 98 mmol/1, p less than 0.006) and the cancer patients (407 +/- 179 mmol/l, p less than 0.001) showed raised levels of serum urate. While serum urate was correlated to serum creatinine in all groups (r = 0.40-0.59, p less than 0.0001) a significant correlation to serum calcium was only seen in the HPT group (r = 0.28, p less than 0.004). This relation persisted also after correction for age, sex and serum creatinine in the multiple regression analysis. Serum creatinine was similar in all groups but significantly correlated to serum calcium only in the HPT subjects (r = 0.29, p less than 0.003). Serum urea was not significantly correlated to serum calcium in any of the groups but was elevated in the cancer group (8.3 +/- 4.4 vs 6.2 +/- 2.9 mumol/l in the control group, p less than 0.0001). This elevation in serum urea seen in the cancer patients might rather be explained by dehydration or catabolism than an impaired kidney function. In conclusion, while serum urate is related to the kidney function both in normo- and hypercalcemia, it also seems to be related to the hypercalcemia in HPT subjects but not in cancer patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Serum levels of 1,25-(OH)2-vitamin D are not altered by long-term supplementation with alphacalcidol (1-OH-vitamin D3). A double-blind, placebo-controlled study.

The endogenous production of 1,25-(OH)2-vitamin D has been estimated to be 1.5 micrograms daily. Despite the use of alphacalcidol (1,25-(OH)2-vitamin D) during more than a decade the long-term effects of the serum levels of 1,25-(OH)2-vitamin D have been poorly investigated. When 1 microgram of alphacalcidol was given daily to 39 non-vitamin D deficient subjects in a double-blind, placebo-controlled study during 4 months no significant effects on the serum levels of 1,25-(OH)2-vitamin D or 25-(OH)-vitamin D were found. The treatment however induced a 50% increase in urinary excretion of calcium (p less than 0.01). In conclusion, long-term supplementation with a physiological dose of alphacalcidol does not influence the serum levels of 1,25-(OH)2-vitamin D, despite a marked effect on urinary calcium excretion.

Adult↗
PubMed1992

Critical care hypercalcemia--a hyperparathyroid state.

Hypocalcemia is a well known finding in critically ill patients. Subsequent occurrence of mild hypercalcemia has also been reported. In order to investigate the incidence and nature of critical care hypercalcemia serum calcium was measured in 83 critically ill ICU patients (TISS score > or = 40) and related to the occurrence of acute renal failure (ARF) and severity of illness, evaluated by the APACHE-II and the multiple organ failure scoring systems. Thirty-two percent of the patients developed hypercalcemia (serum calcium > or = 2.60 mmol/l) during their ICU stay. These hypercalcemic episodes (mean maximal value 2.71 +/- 0.12 mmol/l) were more common and occurred earlier in patients with co-existing ARF. However, multiple regression analysis showed the number of failing organ systems in the first days to be the best predictors for later occurrence of hypercalcemia (p < 0.0001). When serum parathyroid hormone (PTH) was measured in 6 of the patients without ARF during their hypercalcemic episodes, PTH was not suppressed but slightly elevated, to a similar extent as in patients with mild primary hyperparathyroidism. In conclusion, a high incidence of hypercalcemia was found in critically ill ICU patients. The hypercalcemia was mild and was more frequently found in patients with co-existing renal failure. The most powerful predictor to later occurrence of hypercalcemia was however the severity of the illness in itself. The raised levels of PTH found during the hypercalcemic episodes suggest ICU hypercalcemia to be caused by parathyroid overactivity.

Acute Kidney Injury↗