Progesterone induces calcitonin gene expression in human endometrium within the putative window of implantation

The human endometrium acquires the ability to implant the developing embryo within a specific time window that is thought to open between days 19-24 of the secretory phase of the menstrual cycle. During this period the endometrium undergoes pronounced structural and functional changes induced by the ovarian steroids, estrogen and progesterone, that prepare it to be receptive to invasion by the embryo. The identification of reliable biochemical markers to assess this critical receptive phase in the context of the natural cycle remains one of the major challenges in the study of human reproduction. Our previous studies in a rat model system demonstrated that the expression of calcitonin, a peptide hormone involved in calcium homeostasis, is transiently induced by progesterone in the glandular epithelium at the onset of implantation. Attenuation of calcitonin synthesis in the uterus during the preimplantation phase by administration of calcitonin antisense oligodeoxynucleotides severely impairs implantation of rat embryos, suggesting that this peptide hormone plays a critical role in uterine receptivity. To investigate whether calcitonin is also expressed in the human endometrium during implantation, we monitored the spatio-temporal expression of calcitonin on various days of the menstrual cycle. Our studies employing RT-PCR showed that calcitonin messenger ribonucleic acid is expressed in human endometrium during the postovulatory midsecretory phase (days 17-25) of the menstrual cycle, with maximal expression occurring between days 19-21. Very little calcitonin expression was detected in the endometrium in either the preovulatory proliferative (days 5-14) or the late secretory (days 26-28) phase. In situ hybridization and immunocytochemical analyses localized the calcitonin expression predominantly in the glandular epithelial cells of the endometrium. Our studies further showed that calcitonin expression in the human endometrium is under progesterone regulation. Treatment of women with an antiprogestin, mifepristone (RU-486), drastically reduced calcitonin expression in the endometrium. Collectively, these findings reveal that progesterone-induced expression of calcitonin in the secretory endometrium temporally coincides with the putative window of implantation in the human.     

Effect of porcine calcitonin in primary hyperparathyroidism (author's transl)

In order to investigate the effect of calcitonin (CT) on calcium and phosphorus metabolism in primary hyperparathyroidism (PHP), porcine calcitonin (80 MRC units) was injected intramuscularly at 9:00 a.m. and 5:00 p.m. for 10-14 days in 7 patients with parathyroid adenoma. Fasting blood specimens were drawn at 8:00 a.m. every other day and 24 hour urine samples were collected through out control and test days. To examine the acute effect of CT, blood and urine were checked several times until 8 hours after the first injection. A fall in the fasting serum calcium level observed in 5 patients during the repeated administrations of CT, as well as that observed in 6 patients within 6 hours after the first injection, showed a significant correlation with the initial serum calcium level. Serum phosphorus concentration decreased in all patients 6 hours after the first injection, while fasting levels seemed to remain unchanged. During the repeated administrations, urinary excretion of calcium and phosphrus decreased correspondingly with the fall in serum calcium levels, although no definite tendancy was observed within 8 hours after the first injection. Fasting serum PTH levels during the repeated administrations were measured in 2 patients. In a patient whose serum calcium returned to the initial level on the 7th day of administration, a gradual rise of PTH was observed, while in another patient whose serum calcium was kept lower than the initial level, PTH remained almost unchanged. These results indicate that, under such a condition where there is marked increase of bone resorption as PHP, repeated administrations of CT bring about not only a hypocalcemic effect but also the reduction of calcium and phosphorus excretion through a decreased filtered load. In addition, it was suggested that, in some cases of PHP, the hypocalcemic effect of CT may be abolished by an increase of PTH secretion from the parathyroid glands during long-term administration.     

Clinical, haematological, metabolic and endocrine traits during the first three months of life of suckling simmentaler calves held in a cow-calf operation

Newborn suckling Simmentaler calves (10 males and 9 females) in a cow-calf operation were examined from birth up to the age of 3 months. The average daily gain from 47 to 120 kg was 0.86 kg. Except for higher average daily weight gains and insulin-like growth factor-I concentrations and lower thyroid hormone levels in male than female calves, there were no significant sex differences. Plasma glucose, total protein and immunoglobulin G concentrations increased on day 1 of life, thrombocyte number and plasma triglyceride concentrations rose during the first 7 days, whereas lymphocyte and monocyte percentage and plasma inorganic phosphorus, phospholipid, cholesterol and albumin concentrations increased during the first 14 or 21 days and then remained elevated. Eosinophil percentage increased after 3 weeks and insulin-like growth factor-I concentrations increased over the whole growth period. There were transient elevations of plasma glucagon concentrations up to day 14, of the activity of alkaline phosphatase transiently up to day 7 and of gamma-glutamyltransferase, aspartate aminotransferase and lactate dehydrogenase activities on day 1 of life. Plasma iron concentration transiently decreased up to day 28 and creatine kinase activity up to day 7. Total white blood cell number, neutrophil percentage, packed cell volume and concentrations of haemoglobin, calcium, magnesium (after a transient rise on day 1), non-esterified fatty acids, bilirubin, creatinine, triiodothyronine and thyroxine decreased from birth up to days 42, 56, 28, 28, 21, 84, 14, 14, 7, 14 and 7, respectively. Basophil percentage and concentrations of beta-hydroxybutyrate, urea and insulin did not exhibit significant age-dependent changes. The behaviour of most traits in the first weeks was the same in suckling calves under study as in non-suckling pre-ruminant calves. However, packed cell volume, red blood cell number, haemoglobin and plasma iron concentrations were higher, whereas glucose and insulin concentrations were lower than normally found in veal calves. On the other hand, concentrations of glucose, insulin and insulin-like growth factor-I in suckling calves in the third month of age were higher than can normally be measured in breeding calves.     

Attenuation of calcitonin gene expression in pregnant rat uterus leads to a block in embryonic implantation

The peptide hormone calcitonin plays a key role in calcium homeostasis in many tissues, such as bone and kidney. Our previous studies revealed that the expression of calcitonin is dramatically induced in the glandular epithelium of rat uterus between days 3-5 of pregnancy before the onset of blastocyst implantation on day 5. Calcitonin expression is switched off once implantation has progressed to day 6. The coincidence in timing suggested that calcitonin may function as a regulatory signal in the uterus during the early events leading to implantation. Here we report that the implantation stage-specific expression of calcitonin can be specifically attenuated by administering antisense oligodeoxynucleotides (ODNs) directed against exon IV of calcitonin messenger RNA into the uterine horns on day 2 of gestation. The loss of calcitonin messenger RNA and protein expression upon antisense ODN treatment is accompanied by a severe impairment in implantation of embryos. Based on the observations that 1) treatment with two different antisense ODNs possessing different base compositions produced similar phenotypes; and 2) treatment with the complementary sense ODNs did not affect either calcitonin expression or implantation, we conclude that the effects of antisense ODNs on calcitonin expression and implantation are specific and functionally linked. Our study strengthens the hypothesis that a transient expression of calcitonin in the preimplantation phase uterus is critical for blastocyst implantation.     

Prevention of bone loss induced by thyroxine suppressive therapy in postmenopausal women: the effect of calcium and calcitonin

Although controversies exist on the possible adverse effect of T4 on bone mass, most studies reported bone loss in estrogen-deprived postmenopausal women taking suppressive doses of T4. We prospectively studied 46 postmenopausal women with carcinoma of thyroid for 2 yr to evaluate the rate of bone loss and assess whether calcium supplementation with or without intranasal calcitonin was able to decrease the rate of bone loss. All patients were receiving a stable dose of L-T4 (170 +/- 60 micrograms/day or 3.0 +/- 1.4 micrograms/kg.day) for more than 1 yr. All had TSH levels of 0.03 mIU/L or less and an elevated free T4 (FT4) index, but normal T3 levels. The calcium intake was low and averaged 507 +/- 384 g/day as assessed by dietary recall. The subjects were randomized into three groups: 1) intranasal calcitonin (200 IU daily) for 5 days/week plus 1000 mg calcium daily, 2) calcium alone, or 3) placebo. Total body and regional bone mineral density were measured by a dual energy x-ray absorptiometry bone densitometer at 6-month intervals. The results showed that both groups 1 and 2 had stable bone mass, whereas patients in groups 3 showed significant bone loss at the end of 2 yr (lumbar spine, 5.0%, hip, 6.7%, trochanter, 4.7%; Ward's triangle, 8.8%; P < 0.05), with bone mineral densities at all four regions lower than those in the other two groups (P < 0.05). There were no differences between groups 1 and 2. All three groups had elevated osteocalcin levels compared with age-matched reference controls. At 1 yr, the osteocalcin level decreased in groups 1 and 2, but remained significantly raised in group 3. No significant changes were detected in the bone-specific alkaline phosphatase levels. Urinary hydroxyproline excretion increased in group 3 at the end of 2 yr, but remained the same in groups 1 and 2. In conclusion, T4-suppressive therapy was associated with bone loss in postmenopausal women, which could be prevented by either calcium supplementation or intranasal calcitonin, although the latter did not provide additional benefit compared to calcium alone. However, careful titration of T4 dosage to maintain biochemical euthyroidism is a better way to avoid the adverse effect of T4 on bone.     

Absorption of inorganic phosphate in the human jejunum and its inhibition by salmon calcitonin

The jejunal absorption of inorganic phosphate (P) was studied under basal conditions and during the intravenous infusion of synthetic salmon calcitonin (SCT) in normal subjects. Net P absorption increased as the intraluminal P concentration was raised. At intraluminal P concentrations equal to or above the plasma P level P absorption manifested first order kinetics. At intraluminal P concentrations below the plasma P level, net P absorption was non-linear presumably due to the movement of P from plasma to the lumen down a chemical gradient. A net secretion of water and electrolytes occurred in six normal subjects given SCT (250 ng/kg/hr) while saline infusion instead of SCT had no effect on jejunal absorption. Along with the secretory effect SCT reduced calcium and P absorption by 58% and 62% respectively, without any significant fall in the serum levels of calcium or P. The jejunal response to SCT was reproduced twice in a hypoparathyroid subject showing that endogenous parathyroid hormone was not involved in this effect. Calcium and P absorption were positively correlated with water movement suggesting that the observed changes in calcium and P absorption are due primarily to SCT-induced secretion of water. It is concluded that SCT induces a net secretion of water and ions while simultaneously reducing calcium and P absorption.     

Acute responsiveness to calcitonin in chronic renal failure

The acute effect of porcine calcitonin was tested in 17 patients undergoing chronic haemodialysis. In normal adults calcitonin has no effect on plasma calcium or phosphate levels, but in nine patients both concentrations were substantially reduced after calcitonin. This hypocalcaemic and hypophosphataemic effect was a function of the initial plasma phosphate level but was unrelated to the initial plasma calcium level. Plasma hydroxyproline levels were not significantly different in the two groups an were unaffected by calcitonin. In 11 patients fasting plasma calcitonin levels were undetectable with an assay sensitive to 0-1 mug/1. Calcitonin seems to have an acute effect in chronic renal failure which may not operate by arresting bone resorption but is dependent on the plasma phosphate concentration.     

Validation of computerized Swedish dog and cat insurance data against veterinary practice records

Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis, widespread axonal degeneration, and infiltration by polymorphnuclear granulocytes and OX42-positive macrophages were observed in the lesion site. By 7 days p.o., low affinity nerve growth factor receptor-positive Schwann cells, from activated spinal roots, were identified as they migrated far into the lesion. Between 7 and 14 days p.o., the overlapping processes of Schwann cells within the macrophage-filled lesion formed a glial framework which was associated with extensive longitudinally orientated ingrowth by many neurofilament-positive axons. Relatively few of these axons were calcitonin gene-related peptide (CGRP)-, substance P (SP)-, or serotonin (5HT)-positive; however, many were glycinergic or gamma aminobutyric acid (GABA)ergic. At 21 and 28 days p.o. (the longest survival times studied), a reduced but still substantial amount of orientated Schwann cells and axons could be detected at distances of up to 5 mm within the lesion. Glial fibrillary acidic protein (GFAP) immunoreactivity demonstrated the slow formation of astrocytic scarring which only became apparent at the lesion interface between 21 and 28 days p.o. The current data suggest the possibility of developing future therapeutic strategies designed to maintain or even enhance these spontaneous and orientated regenerative events.     

Childhood sexual abuse and current suicidality in college women and men

The effects of retinoic acid (RA) on osteoblastic differentiation and activity were studied in fetal rat calvaria cells cultured for up to 24 days. Fetal bovine serum used for the experiments was treated with an anion-exchange resin to remove endogenous RA. The depletion of RA in the treated serum was confirmed by high-performance liquid chromatography and tritiated RA tracing. Under the culture conditions employed, the continuous presence of RA for 14 days at 10(-9) mol/l or higher decreased both alkaline phosphatase (ALP) activity on day 12 and the number of bone nodules on day 14 in a dose-dependent manner. Short-term (24 h) exposure to RA at 10(-8) mol/l, which is a physiological concentration, decreased and increased the levels of ALP and osteopontin mRNA on day 6, respectively. Retinoic acid at 10(-8) mol/l also increased the level of osteocalcin mRNA on day 12. However, these effects were not obvious at later stages (days 18 and 24). At a high concentration (10(-6) mol/l), RA increased the level of osteopontin mRNA on day 6 and decreased the levels of ALP and osteocalcin mRNA irrespective of culture period. These results suggest that, at physiological concentrations, RA suppresses the differentiation of osteoprogenitor cells and regulates osteoblastic functions.     

Telomerase activity correlates with growth of transplantable osteosarcomas in rats treated with cis-diammine dichloroplatinum or the angiogenesis inhibitor AGM-1470

To determine the role of telomerase activity in the growth of tumors in rats undergoing chemotherapy, a comparison of the volumes of telomerase-positive transplantable osteosarcomas was made in rats treated with the antineoplastic agent cis-diammine dichloroplatinum (CDDP) or the angiogenesis inhibitor O-(chloroacetylcarbamoyl)fumagillol (AGM-1470). Male F344 rats, 8 weeks old, received transplants of macroscopic lung metastatic nodules into the subcutaneous back space and treatment was started on day 14 thereafter. CDDP was injected i.v. at doses of 0, 0.625, 1.25 and 2.5 mg/kg body weight (b.w.) and AGM-1470 was administered at total doses of 0, 2.5, 5 and 10 mg/kg b.w. over 2 weeks by osmotic pumps, also implanted into the subcutaneous back space, but remote from the transplanted tumors. On day 28, all animals were killed for measurement of transplanted tumor size and determination of telomerase activities by telomeric repeat amplification protocol (TRAP) assay. The results showed telomerase activity to be highly correlated with the treated/non-treated (T/C) tumor size ratio (r = 0.96, P < 0.0001). In a second experiment, CDDP at 2.5 mg/kg b.w. and AGM-1470 at 10 mg/kg b.w., these being the most effective doses, were given as in the first experiment, and animals were serially killed on days 14, 21, 28, 35 and 42. Tumors in rats treated with CDDP and AGM-1470 showed 18.2% and 20.5% of the control telomerase activity on days 35 and 21, respectively, when tumor growth was inhibited. However, on day 42, the activities increased to 46.5% and 92.5%, this correlating with re-growth (r = 0.73, P < 0.0001). These results suggest that decline of telomerase activity may be involved in tumor growth retardation induced by chemotherapeutic agents. This possibility clearly warrants further mechanistic studies.     

An efficient method to detect calcitonin mRNA in normal and neoplastic rat C-cells (medullary thyroid carcinoma) by in situ hybridization using a digoxigenin-labeled synthetic oligodeoxyribonucleotide probe

We report here an efficient and rapid method for the specific detection of calcitonin in tumor C-cells of medullary thyroid carcinoma (MTC). This occasionally aggressive tumor arises from the endocrine thyroid C-cells. Its principal marker is calcitonin, the predominant C-cell secretion, which is detected in patients and in our animal model by radioimmunoassay of the plasma, as well as by immunohistochemistry of thyroid tissues. Although calcitonin is easily detectable in normal C-cells, its content is greatly reduced in tumor cells owing to the disappearance of the secretory granules that store the mature peptide. This finding suggests cell dedifferentiation correlated with an increasing aggressivity of the tumor. We therefore developed a rapid detection of calcitonin mRNA by in situ hybridization on routine paraffin sections, using a synthetic oligodeoxyribonucleotide probe labeled with digoxigenin-dUTP. The reaction was detected with an anti-digoxigenin antibody conjugated with alkaline phosphatase, and the enzyme catalyzed the appearance of a dark blue color. The signal was exclusively restricted to the normal, hyperplastic, and tumor C-cells. It was specific, as increasing concentrations of the unlabeled oligonucleotide led to progressive disappearance of the reaction. Its sensitivity was slightly diminished as compared with corresponding frozen sections, but the intensity of the signal was quite acceptable. High levels of calcitonin mRNA were found in all normal and hyperplastic C-cells. They were increased in most of the tumor MTC cells, which did not correlate with the amount of intracellular peptide stores but explained the abnormally high basal levels of circulating calcitonin of the tumor-bearing rats. ISH is therefore of greater value than ICC for an early anatomopathological detection of this tumor. Our data show that the tumor cells are not "dedifferentiated." They only lack the granular compartment storing the mature peptide before exocytosis, but CT biosynthesis and the rest of the secretory process seem to be complete. Our results suggest that factors expressed in malignant C-cells affect basic cell mechanisms involved in the storage of the mature calcitonin, rather than the expression of the CALC gene.     

Clinical biochemistry, haematology and body weight in piglets

Reference ranges for clinical biochemical parameters commonly investigated in pigs were determined in one- (day 1), 21- and 35-day old piglets. The mean and standard deviation were also estimated for body weight, and haematological and clinical biochemical parameters at these ages. The piglets were divided into 2 investigation groups according to whether they had a haemoglobin concentration < or = 80 g/l ("anaemic group") or > 80 g/l ("normal group") on days 14, 21 and 28. The "anaemic group" was compared to the "normal group" on days 21 and 35. Many of the clinical biochemical parameters varied according to age. Some of the enzymes had high average values and wide reference ranges in piglets, especially on day 1, compared to the reference ranges for sows given in the literature. The reference ranges for some of the metabolic parameters were broader on day 1 than later in the preweaning period. The reference ranges for albumin, total iron-binding capacity and serum iron were, however, lower and more narrow on day 1. On days 21 and 35, relatively high values for phosphorus must be considered "normal" compared to the figures given in the literature for adult pigs. The other minerals seemed to be quite unaffected of age, but some were affected by anaemia. The anaemic piglets had lower average serum iron but higher total iron-binding capacity than the "normal" piglets on days 21 and 35. However, variation between piglets gave wide reference ranges, indicating that these parameters will only have limited usefulness in detecting iron deficiency anaemia in piglets. The electrolytes seemed also to be affected by the existence of anaemia. The body weight and leukocyte counts were significantly lower in the "anaemic group" than the "normal group" on day 35, while the greatest differences in clinical biochemical parameters between the groups were found on day 21, when the piglets in the "anaemic group" were most severely anaemic. Although these piglets suffered from severe iron-deficiency anaemia, only a few clinical biochemical parameters were affected, and the differences between groups were mostly small.     

Acute effects of chundosunbup qi-training on blood concentrations of TSH, calcitonin, PTH and thyroid hormones in elderly subjects

The present study investigated how the systemic treatment of a programmed exercise, ChunDoSunBup (CDSB) Qi-training, affects the secretion of thyroid and parathyroid hormones in elderly subjects (10 male and 5 female). Plasma concentrations of thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), parathyroid hormone (PTH), ionized calcium, and calcitonin were determined. CDSB Qi-training induces a slight increase in TSH. Both T4 and T3 were increased at the mid-time of CDSB Qi-training (p < 0.05). There were significant correlations only between T3 and T4 at mid-training. This shows that increase in the plasma level of T3 was associated with the secretion of T4. The plasma concentrations of calcitonin and PTH were increased at mid-time and post-time of CDSB Qi-training. But ionized calcium was decreased slightly by CDSB Qi-training. These results suggest that Qi-training modulates the secretion of thyroid hormones, calcium metabolism, and parathyroid hormones in the elderly. However, whether the long-term practice of CDSB Qi-training might change bone metabolism and have longitudinal effects on the thyroid hormone of the elderly need further investigation.     

Experimental autotransplantation of the parathyroid gland

The lateral parathyroid gland of the rabbit was resected and autotransplanted under an ear skin flap. A skin flap at the opposite side was used as control. The success of autotransplantation was established by microangiography of the transplant and by measuring plasma concentrations of parathyroid hormone (PTH), calcium and phosphorus. After 4 months the animals were killed and the transplant was studied histologically and by electron microscopy. Fourteen animals were included in the study. There was an increase in PTH derived from the transplanted gland after 4-6 postoperative days. All animals developed hypocalcaemia during the 3 days after transplantation. There were no significant changes in serum phosphorus. Transplantation did not alter the morphology of the distribution of the cells in the transplanted gland, which functioned normally after the fourth postoperative day.     

The influence of salmon calcitonin on the soluble form of VCAM-1 (CD 106) and E-selectin (CD 62E) in serum of patients with atopic bronchial asthma

The aim of the study was to evaluate the effect of salmon calcitonin (CT) on serum level of soluble form of VCAM-1 (sVCAM-1 = soluble vascular cell adhesion molecule-1) and E-selectin (sE-selectin = soluble E-selectin) in patients with atopic bronchial asthma. Twenty-four individuals divided into 4 groups (6 persons each) were investigated. The first group consisted of patients with chronic moderate bronchial asthma, the second and third groups consisted of patients with mild bronchial asthma and the fourth group K consisted of healthy individuals. The patients of the first and second group were treated with CT at a dose of 100 i.v./days s.c. for three days. The patients of the third group were given placebo (phychological saline) in similar way as CT. The indices were measured before the treatment with CT or placebo and on the 4th day of the treatment. It was found that CT treatment decreased sVCAM-1 in serum only in the patients of the first group (p < 0.05) but had no effect upon sE-selectin level. The obtained results suggest that CT interfered into mechanisms of inflammation involving adhesion molecules in patients with bronchial asthma.     

Abnormalities of calcium, phosphorous and vitamin D metabolism with proximal renal tubular dysfunction in subjects environmentally exposed to cadmium

Calcium, phosphorus and vitamin D metabolism were examined in 21 male and 13 female subjects with renal tubular dysfunction in the cadmium-polluted Jinzu River basin in Toyama prefecture, Japan. Multiple proximal renal tubular dysfunction was detected in all subjects showing increased FE beta 2-m and FFua, generalized aminoaciduria and renal glucosuria. Reduced ability of tubular reabsorption of phosphate resulted in hypophosphatemia in 31% of the women. Despite decreased tubular reabsorption of calcium, the level of serum calcium remained normal in all subjects. Serum 1,25-dihydroxyvitamin-D [1,25(OH)2D], which is produced in the proximal tubules through 1 alpha-hydroxylation from 25-hydroxyvitamin-D [25OHD], was normal or increased to more than 60pg/ml. The serum level of 1,25(OH)2D was inversely related to creatinine clearance in both the men (p < 0.05) and women (p < 0.01). Serum iPTH was slightly increased to more than 0.9 mg/ml, whereas the levels of other hormones, including 25OHD, calcitonin, thyroxine (T4) and triiodothyronine (T3) were normal. The serum alkaline phosphatase activity and serum osteocalcin concentration were significantly increased compared to those of controls in both sexes. Bone loss detected by the measurement of bone density was prominent in female subjects. These results support the hypothesis that the serum phosphate concentration is more important than the serum concentration of 1,25(OH)2D for abnormalities of bone metabolism in cadmium-induced renal tubular dysfunction.     

The current role of preoperative arteriography in free fibula flaps

Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal, and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell surface calcium-sensing receptor. We describe the first therapeutic use of a novel molecule, a calcimimetic, that has agonist action at the calcium-sensing receptor. A 78-yr-old man with parathyroid carcinoma was admitted with hypercalcemia, markedly elevated PTH, and a change in mental status. He was treated for 17 days with conventional therapy, which included saline hydration, furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day 30, saline and furosemide were discontinued. He was discharged on hospital day 40. With several dose adjustments, he has been treated with monotherapy calcimimetic for over 600 days and has not required any other interventions for his parathyroid carcinoma. Mean daily precalcimimetic treatment values of serum ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to 1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51 mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH, serum calcium has remained high, but lower than the admission level and acutely responsive to changes in calcimimetic doses. This compound, a calcimimetic, the first of a new class of compounds with activity at the calcium-sensing receptor, has been used to treat a patient with parathyroid carcinoma. During 2 yr of treatment, no adverse clinical effects have been observed, and it appears to have been effective at controlling hypercalcemia.     

Control of calculus formation by a dentifrice containing calcium lactate

This study has been carried out in order to elucidate the clinical significance of serum osteocalcin measurement. The changes of this marker paralleled those of serum total alkaline phosphatase activity (a marker of bone formation) following parathyroidectomy in hyperparathyroid patients with skeletal involvement. Furthermore, the percentage decrease of serum osteocalcin levels in respect to basal values (85 +/- 12), and the percentage decrease of serum alkaline phosphatase activity levels (82 +/- 7) were significantly lower (p < 0.001) in respect to that of the 24-h hydroxyproline/creatinine ratio (42 +/- 14) one week after parathyroid surgery. Instead, changes of serum osteocalcin levels were similar to those of serum free hydroxyproline (considered to be a marker of bone resorption) following acute calcitonin infusion in normal subjects. These results imply that the antibody used in our assay might recognize not only the entire osteocalcin molecule, but also small epitopes released during the process of bone matrix resorption. Alternatively, if we consider serum osteocalcin only as a marker related to some processes of bone formation, the experiment carried out on normal subjects strongly supports the evidence of calcitonin receptors in osteoblastic surfaces.