Acute regulation of parathyroid hormone by dietary phosphate

Secondary hyperparathyroidism in chronic renal failure is stimulated by dietary phosphate (P(i)) loading and ameliorated by dietary P(i) restriction. We investigated the rapidity of the response of serum parathyroid hormone (PTH) to changes in dietary P(i). When uremic rats adapted to a high P(i) diet (HPD) were fed a single meal of low P(i) diet (LPD), plasma PTH fell 80% within 2 h; plasma P(i) fell 1 mg/dl with no change in plasma ionized Ca (ICa). When uremic rats on the HPD were gavaged with LPD, PTH fell 60% within 15 min; plasma P(i) fell by 3.0 mg/dl with no change in total plasma Ca. However, HPD gavage increased PTH by 80% within 15 min with no change in plasma P or Ca, suggesting that the response may be independent of altered plasma P(i). Duodenal infusion of sodium P(i) increased PTH twofold within 10 min, with no change in ICa but an increase in plasma P(i), whereas duodenal infusion of NaCl had no effect on any of these parameters. Intravenous infusion of sodium phosphate also increased PTH within 10 min with no change in plasma ICa; intravenous NaCl had no effect. Additionally, duodenal infusion of phosphonoformate, a nonabsorbable phosphate analog, increased PTH fourfold within 5 min, but did not change plasma P or ICa. These findings indicate that oral P(i) increases PTH release in vivo more rapidly than previously reported; this response may be from both plasma phosphate and an additional signal arising from the gastrointestinal tract.     

The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide‐mediated vasorelaxation in BALB/c mice

There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L‐NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1–34] (80 µg/kg/day) or L‐NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro‐CT, histomorphometry and three‐point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co‐treatment with L‐NAME blocked the action of PTH on blood flow, whereas L‐NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co‐treatment with L‐NAME restricted the PTH‐stimulated increase in cortical bone formation but had no clear‐cut effects in trabecular bone. Co‐treatment with L‐NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO‐mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. © 2016 The Authors. Cell Biochemistry and Function published by John Wiley & Sons, Ltd.     

Effect of parathyroid hormone on the increase in serum glucose and insulin levels after a glucose load to thyroparathyroidectomized rats.

Thyroparathyroidectomy (TPTX) caused a significant increase in serum glucose and a corresponding fall in serum calcium in both fed and fasted rats. The increase in serum glucose, induced by TPTX, was markedly potentiated by a single intraperitoneal administration of calcium (2 mg/100 g BW) which caused a significant elevation of serum calcium in thyroparathyroidectomized rats. Parathyroid hormone (PTH; 20 U/100 g BW) administered subcutaneously to thyroparathyroidectomized rats, caused a significant decrease in serum glucose (0.1 g/100 g BW) to sham-operated rats significantly increased both serum glucose and insulin. The rise of serum glucose produced by a glucose load was markedly potentiated by TPTX, but the increase in serum insulin was not promoted significantly. The administration of PTH decreased both serum glucose and insulin levels increased by a glucose load to thyroparathyroidectomized rats, in a dose-dependent manner. The administration of calcitonin (80 MRC mU/100 g BW) significantly prevented the effect of PTH to decrease serum glucose after a glucose load to thyroparathyroidectomized rats, and calcitonin increased serum insulin. These results suggest that the effect of PTH on serum glucose does not involve insulin secretion.     

Long-term systemic administration of human recombinant interleukin-1beta induces a dose-dependent fall in circulating parathyroid hormone in rats.

The synergism/antagonism between interleukin (IL)-1beta and parathyroid hormone (PTH) has been the subject of in vitro and in vivo work, but a possible direct action of the cytokine on PTH release has not been reported. We have investigated the effect of a continuous infusion of human recombinant IL-1beta (rIL-1beta) on circulating PTH during a 14-day period in 7-week-old female rats. This time interval was chosen in order to exclude initial hypercalcemia and to enable data collection under steady-state conditions. Five groups of 20 animals each had miniosmotic pumps (Alzet 2002, 200 microl) implanted subcutaneously and primed to release either distilled water (controls) or 100, 500, 1,000 and 2, 000 ng/24 h of rIL-1beta. Blood was drawn on days 1 and 14 for PTH, corticosterone and Ca2+ determinations. Adequate biological activity of the infused rIL-1beta was supported by elevated rectal temperature records and significant elevations of plasma corticosterone on day 14. The 100-ng dose had no effect but 500-2, 000 ng rIL-1beta/24 h significantly reduced plasma PTH in a dose-dependent manner down to 54% of basal value (20.4 +/- 1.1 vs. 15.3 +/- 1.4 pg/ml for 500 ng, p < 0.005; 20.5 +/- 1.3 vs 12.3 +/- 1.1 for 1,000 ng, p < 0.001, and 19.5 +/- 2.0 vs. 10.6 +/- 1.1 pg/ml for 2,000 ng, p < 0.0008). Despite these findings, no differences in blood Ca2+ could be detected between treated animals and controls. The following conclusions can be inferred from the foregoing: Systemic administration of rIL-1beta to rats induced a dose-dependent fall in circulating PTH without altering calcemia, calling into question the biological relevance of the former finding. Although the recorded PTH depression may indeed not have been severe enough to cause hypocalcemia, it can be hypothesized that osteoclast activation by rIL-1beta would enhance bone mineral release into the pool compensating for depressed PTH activity.     

Dietary boron supplementation enhances the effects of estrogen on bone mineral balance in ovariectomized rats

The present study investigated whether boron would enhance the action of 17β-estradiol (E₂) or parathyroid hormone (PTH) on bone mineral balance in ovariectomized (OVX) rats. Forty-three days after OVX, the rats were treated for 5 wk with vehicle, boron (5 ppm as boric acid), E₂ (30 μg/kg/d, sc), PTH (60 μg/kg/d, sc), or a combination of boron and E₂ or PTH. Bone mineral balance was assessed by measuring apparent absorption, excretion, and retention of calcium (Ca), phosphorus (P), and magnesium (Mg). Serum Ca, P, Mg, and osteocalcin were also measured in this experiment. Boron alone had no effects on food consumption, weight gain, bone mineral balance, and serum levels of Ca, P, Mg, and osteocalcin. E₂ alone increased serum P and Mg and decreased serum osteocalcin, but it had no effect on bone mineral balance. The combination of boron and E₂ markedly improved apparent absorption of Ca, P, and Mg. In addition, the combination treatment increased the apparent retention of Ca and Mg (but not P) and also increased serum Ca and Mg but not serum P. On the other hand, boron cotreatment did not prevent the E₂-induced reduction in serum osteocalcin in OVX rats. PTH alone significantly increased serum Ca, P, Mg, and osteocalcin concentrations, although it had no effect on bone mineral balance. Contrary to the boron-E₂ combination treatment, the combination of boron and PTH did not enhance bone mineral balance. However, inasmuch as boron-PTH cotreatment did not enhance the stimulatory action of PTH on serum Ca, P, and osteocalcin, boron completely abolished the stimulatory effect of PTH on serum Mg. In conclusion, we have demonstrated for the first time that although boron by itself has no effect on bone mineral homeostasis, it appears to have synergistic enhancing effects on the action of E₂ on Ca and Mg homeostasis in OVX rats.     

Hypercalcemia in glucocorticoid withdrawal

We found severe hypercalcemia in the course of hydrocortisone withdrawal in a patient who had undergone unilateral adrenalectomy to resect a cortisol-hypersecreting adenoma. Serum calcium gradually but progressively increased after unilateral adrenalectomy. Severe hypercalcemia developed on the 77th postoperative day (the 15th day after discontinuing hydrocortisone replacement). The serum concentration of calcium, PTH, 25(OH)D, and 1,25(OH)2D were 8.0 mEq/l, less than 100 pg/ml, 10.1 ng/ml and 29.6 pg/ml, respectively. This hypercalcemia was accompanied by marked urinary hydroxyproline excretion and less calcium excretion in the urine than the prevailing level of serum calcium. Serum concentrations of 25(OH)D, 1,25(OH)2D and PTH were not elevated during the severe hypercalcemia. We concluded that the hypercalcemia in this patient was due in part to enhanced bone resorption and increased renal tubular reabsorption of calcium as a result of glucocorticoid withdrawal, but not to the elevation of serum PTH or serum 25(OH)D and serum 1,25(OH)2D.     

Parathyroid hormone and calcitonin secretion in man: effect of dopamine agonists and antagonists

This study was undertaken to evaluate the physiological role, if any, of dopamine (DA) in modulating parathyroid hormone (PTH) and calcitonin (CT) secretion in man. Infusion of DA (5 micrograms/kg/min) into 6 normal men, decreased serum immunoreactive prolactin (iPRL) and concomitantly increased serum iPTH to 140 +/- 6.8% of baseline (P less than 0.01) at 30 min, with decline thereafter, despite continuation of the DA infusion. Serum iCT levels did not significantly change. Chlorpromazine (50 mg IM), decreased serum iPTH to 75 +/- 5.4% and 79 +/- 3.7% of baseline (P less than 0.01) at 30 and 60 min, respectively, associated with an increase in iPRL. There was subsequent return of iPTH to baseline even though iPRL remained elevated. iCT levels did not significantly change. These observations would suggest that DA may play a physiological role in iPTH, but not iCT, secretion. However, infusion of more nearly physiological doses of DA (0.02, 0.2, and 2.0 micrograms/kg/min) lowered serum iPRL to levels similar to those after the larger DA dose, but with no concomitant increase in either iPTH or iCT. Also, 1) the DA agonist bromocriptine decreased serum iPRL without modifying iPTH or iCT; 2) the DA precursor, levodopa, and the DA antagonist, metoclopramide, had no effect on serum iPTH or iCT levels. These studies suggest that 1) the transient stimulatory effect of DA on iPTH secretion is pharmacological, and 2) DA does not have a physiological role in secretion of iPTH or iCT in man.     

Effect of age and Gender on Fasting and Food-Stimulated Levels of Calcitonin,Parathyroid, and Gastrin Hormones in Healthy Adults

Objective: To investigate the effect of age and gender on basal and food-stimulated serum calcitonin (CT), parathyroid hormone (PTH), and gastrin levels among healthy adults.Methods: Ninety-six healthy adults (76 men and 20 women) aged between 21 and 43 years were recruited. Serum CT, PTH, and gastrin levels were measured after a 9-hour overnight fast, and 1 and 3 hours postprandially.Results: PTH levels decreased early and increased late after feeding. This change was significant in men but not in women. CT levels increased in response to food intake in men but not in women. Gastrin levels were significantly increased after feeding in both men and women. Mean basal and food stimulated CT, PTH, and gastrin levels did not significantly differ between genders. Fasting and post-prandial PTH levels were higher while gastrin levels were lower in older subjects (>30 years old) compared to younger subjects (≤30 years old). Fasting and postprandial CT levels were not significantly different between age groups.Conclusion: Age had a significant effect on fasting and food-stimulated PTH and gastrin hormone levels. The effect of age on PTH levels was independent of baseline vitamin D levels. Men showed significant changes in CT and PTH levels in response to feeding compared to women, although the mean hormone levels were not significantly different between men and women.Abbreviations: CT = calcitonin; MTC = medullary thyroid carcinoma; PTH = parathyroid hormone; SD = standard deviation     

RETRACTED ARTICLE: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor,GcMAF

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32–50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.     

Proliferation of guinea-pig uterine epithelial cells in serum-free culture conditions: effect of 17 beta-estradiol, epidermal growth factor and insulin

The effects of 17 beta-estradiol (E2), epidermal growth factor (EGF) and insulin, alone or in association on guinea-pig uterine epithelial cell proliferation were examined in serum-free culture conditions. Primary cultures of epithelial cells were made quiescent by serum depletion, then incubated in a chemically defined medium. In this medium, insulin increased DNA synthesis but not in a dose-dependent manner for concentrations ranging from 0.2 to 10 micrograms/ml. A significant effect of EGF was found only for the highest concentration tested (100 ng/ml). E2 alone or in the presence of insulin (1 microgram/ml) had no effect whatsoever on the concentration tested (10(-10)-10(-5)M). Insulin (10 micrograms/ml) plus EGF (100 ng/ml) exerted on DNA synthesis and cell proliferation a significant additive effect which was identical to the growth stimulation induced by 10% fetal calf serum. The effects of insulin plus EGF were not modified by the addition of E2. These findings suggest that E2 is not directly mitogenic for uterine epithelial cells in defined culture conditions and that the mitogenic response to optimal concentration of insulin plus EGF is independent of E2.     

Serum 25-Hydroxyvitamin D Deficiency; A Risk Factor for Chronic Kidney Disease in Ambulatory Indigent Patients

ObjectiveTo assess whether 25-hydroxyvitamin D (25[OH]D) deficiency is a risk factor for chronic kidney disease (CKD) in ambulatory indigent patients.MethodsData for all serum 25(OH)D concentrations measured during 2010 in our ambulatory nondialysis-dependent patients were analyzed along with CKD-related parameters. Patients were stratified into groups based on 25(OH)D levels of < 10, 10 to 19, 20 to 29, and ≥ 30 ng/mL. CKD was defined by estimated glomerular filtration rate (eGFR; Chronic Kidney Disease-Epidemiology Collaboration [CKD-EPI] equation) and abnormal urine protein to creatinine ratios. CKD-associated parameters included serum parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25[OH]₂D), alkaline phosphatase, albumin, corrected calcium, and total CO₂ levels.ResultsA total of 2,811 patients had 25(OH)D levels measured. Patients with 25(OH)D levels < 10 ng/mL had significantly increased relative risk (RR) of an eGFR < 15 mL/min/1.73 m² (RR, 4.0), an eGFR of 15 to 29 mL/min/1.73 m² (RR, 2.6), urine protein to creatinine ratio > 3.5 g/g (RR, 5.6), and serum PTH > 100 pg/mL (RR, 2.8) compared to patients with a 25(OH)D level ≥ 30 ng/mL. Patients with 25(OH)D levels of 10 to19 ng/mL had significantly increased RR of a urine protein to creatinine ratio > 3.5 g/g (RR,4.8) and serum PTH > 100 pg/mL (RR, 1.5) compared to patients with 25(OH)D levels ≥ 30 ng/mL.Conclusion25(OH)D deficiency (< 10 ng/mL) was associated with reduced eGFR, nephrotic-range proteinuria, and increased PTH levels in our population of ambulatory urban indigent patients. (Endocr Pract. 2014;20:236-243)     

Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns

Renal parathyroid hormone (PTH) action is often studied at high doses (100 microg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na(+) transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 +/- 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 microg.kg(-1).h(-1)) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na(+) reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli.     

Inhibitory effects of active vitamin D preparations on PTH secretion in rats

To study the effects of various vitamin D preparations on PTH secretion, serum calcium and urinary excretion of cAMP were monitored in conscious perfused rats, and the influences of a bolus iv injection of the preparations on these parameters were examined. Three hours after the administration of 0.25 microgram/kg (0.6 nmol/kg) of 1 alpha, 24(R)-dihydroxycholecalciferol [1 alpha, 24(OH)2D3], the urinary excretion of cAMP decreased to a level compatible with that of parathyroidectomized (PTX) rats (50% of initial value; p less than 0.05) with no change in the concentration of serum calcium (total and ionized). In PTX rats supplemented with bovine PTH (1 U/h), the vitamin D preparation showed no significant effects either on the urinary excretion of cAMP or on serum calcium. These effects were rather specific for active vitamin D preparations, i.e. 1 alpha, 25(OH)2D3 (0.25 micrograms/kg) and 1 alpha OHD3 (1.25-6.25 micrograms/kg). However, 24,25(OH)2D3 (up to 25 micrograms/kg) had no significant effect on these parameters. These results suggest that, in rats, active vitamin D preparations specifically inhibit PTH secretion without causing a significant increase in the serum calcium concentration, reflecting a direct feedback mechanism between active vitamin D metabolite and the parathyroid glands.     

Role of antidiuretic activity in the inhibition of renin secretion by vasopressin in anesthetized dogs

The nature of the activity of vasopressin which is responsible for the inhibition of renin secretion was studied by comparing the effects of vasopressin (AVP) and analogs of AVP in anesthetized water-loaded dogs. Infusion of AVP (1.0 ng/kg/min) increased mean arterial pressure (MAP) and decreased heart rate (HR) and free water clearance (CH2O). Plasma renin activity (PRA) decreased from 11.9 +/- 4.7 to 3.8 +/- 1.7 ng/ml/3 hr (p less than 0.05). A selective antidiuretic agonist, 1-deamino-8-D-arginine vasopressin (1.0 ng/kg/min), which had no effect on MAP or HR but was effective as AVP in decreasing CH2O, decreased PRA from 13.5 +/- 4.6 to 7.0 +/- 2.9 ng/ml/3 hr (p less than 0.05). Infusion of a selective vasoconstrictor agonist, 2-phenylalanine-8-ornithine oxytocin (1.0 ng/kg/min), increased MAP and decreased HR but did not decrease CH2O or PRA. A vasoconstrictor antagonist, d(CH2)5Tyr(Me)AVP (10 micrograms/kg), completely blocked the MAP and HR responses to AVP but did not block the decrease in CH2O or PRA (5.9 +/- 1.8 to 2.9 +/- 1.6 ng/ml/3 hr) (p less than 0.001). Infusion of the 0.45% saline vehicle had no significant effect on MAP, HR, CH2O or PRA. These results indicate that the inhibition of renin secretion by vasopressin in anesthetized water-loaded dogs is due to its antidiuretic activity.     

Effects of xylazine immobilization on biochemical and endocrine values in white-tailed deer

The effect of xylazine hydrochloride on biochemical and endocrine parameters in plasma was examined in adult white-tailed deer (Odocoileus virginianus (Zimmermann]. In the first experiment, seven animals were injected intramuscularly via a blowgun dart with 0.65 mg/kg xylazine (100 mg/ml) and were bled 10, 20, 30, and 60 min post-injection. In the second experiment, eight animals were manually restrained for the first blood sampling and then injected manually and bled as before. Plasma calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase (AP) were measured spectrophotometrically. Plasma parathyroid hormone (PTH), calcitonin (CT), thyroxine (T4), triiodothyronine (T3), and cortisol were measured by radioimmunoassay. Plasma PTH, CT, T4, T3, and AP activity did not differ (P greater than 0.05) during the 1 hr period studied in either experiment. Plasma Ca and P decreased significantly (P less than 0.05) in the second experiment, whereas cortisol levels increased significantly (P less than 0.05) 10 min post-injection in both experiments. The results may have been due to a drug effect or a combined drug and stress effect. It is suggested that xylazine may be safely used as an anesthetic in measuring PTH, CT, T4 and T3, and plasma AP up to 60 min post-injection in deer. Caution should be taken in using xylazine as an anesthetic to study adrenocortical function.     

Stimulatory effect of calcitonin on fatty acid synthesis in the liver of fed rats

The effect of calcitonin (CT) on free fatty acid concentration in the serum and liver of fed rats was investigated. A single subcutaneous administration of CT (synthetic [Asu1,7] eel CT;80 MRC mu/100 g body weight) produced a significant increase in serum free fatty acid concentration. An appreciable effect of CT was observed at a dose of 5 MRC mU/100 g body weight. The hormonal effect was also observed in thyroparathyroidectomized rats. The effect of CT on serum free fatty acid was diminished by fasting. Free fatty acid content in the hepatic cytosol of fed rats was markedly increased by CT administration. The hormonal effect was observed at a dose of 5 MRC mU/100 g body weight. Furthermore, stimulation of fatty acid synthesis caused by intraperitoneal injection of alanine (1.122 mmoles/100 g body weight) was markedly enhanced by administration of CT (5, 20 and 80 MRC mU/100 g body weight). This effect of CT on the liver may be the cause of increased level of fatty acid in the serum. The present results suggest that CT may stimulate synthesis of free fatty acid in the liver of fed rats.     

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.     

有氧运动联合褪黑素对Ⅱ型糖尿病大鼠骨质疏松的影响

目的：观察有氧运动和褪黑素对Ⅱ型糖尿病大鼠骨质疏松的影响。方法：6周龄的成年雌性SD大鼠60只,随机分为安静对照组（N组）10只和Ⅱ型糖尿病模型组50只,N组大鼠不加任何干预,Ⅱ型糖尿病模型组大鼠一次性腹腔注射35 mg/kg链脲佐菌素（STZ）,1周后检测大鼠血糖大于16.7 mmol/L为Ⅱ型糖尿病造模成功,将40只成模大鼠随机分为糖尿病对照组（D）、糖尿病+有氧运动组（DE）、糖尿病+褪黑素组（DM）、糖尿病+有氧运动+褪黑素组（DEM）,每组10只;DE组和DEM组大鼠采用20 min的递增负荷的方式进行跑台有氧运动,训练持续6周,DM组和DEM组大鼠每天灌胃40 mg/kg褪黑素,观察各组大鼠体重、脊椎骨以及左右股骨骨密度（BMD）、观察大鼠血糖、血清丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、血清总钙（Ca）、无机磷（P）和甲状旁腺素（PTH）的变化。结果：与N组相比,D组大鼠体重、血清SOD、GSH-Px水平、血Ca、腰椎和左右股骨BMD显著降低（P < 0.05,P < 0.01）,血糖、血清MDA和血PTH水平显著升高（P < 0.01）,血P无明显变化（P > 0.05）;与D组比较,DE组、DM组大鼠大鼠体重、血清SOD、GSH-Px水平、血Ca、腰椎和左右股骨BMD显著升高（P < 0.05,P <0.01）,血糖、血清MDA和血PTH水平显著降低（P < 0.05,P < 0.01）,血P无明显变化（P > 0.05）,有氧运动和褪黑素同时干预效果更好。结论：有氧运动和褪黑素均能改善糖尿病骨质疏松,且两者联合干预的效果更加显著,其可能与通过提高糖尿病大鼠的抗氧化应激能力,调节糖的代谢从而有效地降低血钙和PTH,改善BMD来缓解骨质疏松有关。     

Hypocalcaemia and serum levels of inorganic phosphorus, magnesium parathyroid and calcitonin hormones in the last month of pregnancy in Awassi fat-tail ewes

Serum levels of calcium (Ca), inorganic phosphorus (P), magnesium (Mg), parathyroid (PTH) and calcitonin (CT) hormones of fat-tail Awassi ewes were determined during the last month of pregnancy. The incidence of hypocalcaemia (HCE) was 13.4% of the obstetrical cases examined. Twenty-six (81.3%) of 32 ewes with HCE were 4 yr of age or older. Significant decreases (p less than 0.01) in serum Ca levels from normal values or controls (n = 6; 10.04 +/- 0.22% (w/w)) to pathological values (4.30 +/- 0.35% (w/w)) caused severe clinical manifestations in 75% of affected ewes. This HCE was accompanied by a significant increase in the PTH level (142.6 +/- 9.1 pmol/l in comparison to 99.7 +/- 9.3 pmol/l in controls, p less than 0.05) and significant decrease in serum CT level (98.2 +/- 7.6 pg/ml in comparison to 144.6 +/- 25.7 pg/ml in controls; p less than 0.05). Intravenous administration of Ca borogluconate yielded normal Ca levels which were accompanied by a decrease in serum PTH levels and an increase in CT levels to normal values.