Vitamin D, Parathyroid Hormone, Insulin Sensitivity and Islet β-Cell Secretory Function in Diabetic Patients from South Kivu in the Democratic Republic of Congo: Cross-Sectional Study

Background: The role of vitamin D and parathyroid hormone in the metabolic profile of type 2 diabetes mellitus in sub-Saharan Africa has not been adequately assessed. The aim of this study was to determine the prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin sensitivity and β-cell secretory function among Congolese type 2 diabetics. Methodology: Fasting glycaemia, fasting insulin, 25OH D3 and human parathyroid hormone (hPTH) were measured in one hundred and eighty-four type 2 diabetic patients followed as outpatients in South Kivu. Levels of 25OH D3 65 pg/ml defined low vitamin D and elevated parathyroid hormone levels, respectively. The HOMA model was used to measure insulin sensitivity and β-cell secretory function. Results: Medians (IQR) were 25.3 (20.4 - 32.4) ng/ml for 25OH D3 and 53.7 (38.4 - 115.7) pg/ml for hPTH. 58.7% of diabetics had insulin resistance, 126 (68.5%) had low vitamin D and 80 (43.5%) had hyperparathyroidism. In multivariate analysis, hPTH (partial r = −0.28;p = 0.0002) and 25OH D3 (partial r = 0.16;p = 0.03) showed an independent association with insulin sensitivity after adjustment for body mass index and waist circumference. Finally, hPTH (partial r = 0.27;p = 0.0002) was the sole determinant of β-cell secretory function. Conclusions: This study confirms the high prevalence of low vitamin D level and secondary hyperparathyroidism and their association with insulin resistance and impaired islet β-cell secretory function among Congolese with type 2 diabetes mellitus. Vitamin D and calcium supplementation should be envisaged for cases of deficiency in this region.

Post Thyroidectomy Assessment of Intact Parathyroid Hormone for Early Prediction of Hypocalcaemia

Background: As the half-life of intact parathyroid hormone (iPTH) is very low, it reflects parathyroid insufficiency within minutes to hours after total thyroidectomy. Therefore, iPTH level assessment in the postoperative period can be used to predict the development of hypocalcaemia. The optimal time point to measure serum iPTH is important for the accurate prediction of hypocalcaemia. Aim: This paper aims to evaluate the ability of iPTH as an early predictive marker of hypocalcaemia and determine which time iPTH is more able to predict postoperative hypocalcaemia. Method: This prospective observational study was conducted in the Department of Otolaryngology-Head & Neck Surgery, BSMMU, Dhaka, from July 2020 to December 2021, with 67 patients who underwent total thyroidectomy. iPTH levels were measured on the day before the operation and at 1 hour, 4 hours, and 24 hours after the operation. S.calcium levels were measured on the day before the operation and 1st postoperative day. All the data were compiled and sorted properly and were analyzed statistically. Results: Postoperative hypocalcaemia developed in 18 cases, with an incidence of 26.9%. Pearson correlation showed a significant correlation between postoperative iPTH at 1 hr, 4 h, and 24 hr with 1st postoperative calcium value. The Receiver operating characteristic (ROC) curve was processed for the postoperative iPTH at 1 hr, 4 h, and 24 hr. The sensitivity, specificity, cut-off value, and mean AUC found 93.9%, 94.4%, ≤14.0, 0.988;95.9%, 94.4%, ≤09.5, 0.993 and 91.8%, 94.4%, ≤11.0, 0.993 respectively. Conclusion: iPTH can be used as an early predictor of post-thy-roidectomy hypocalcaemia. 4 hr iPTH showed more sensitivity and specificity for a cut-off value near the laboratory reference range.

The effect of the ratio of standardized ileal digestible lysine to metabolizable energy on growth performance,blood metabolites and hormones of lactating sows

A total of 335 lactating sows （Landrace x Large White） were used in two experiments to determine the optimum ratio of standardized ileal digestible lysine （SID-Lys） to metabolizable energy （ME） for mixed parity sows during lactation. In Exp. 1, 185 sows （weighing an average of 256.2 ± 6.5 kg and having an average parity of 3.4 ± 0.3） were allocated to one of six experimental diets in a completely randomized block design within parity groups （1, 2, and 3＋）. The experimental diets were formulated to contain 3.06, 3.16, 3.20, 3.25, 3.30 or 3.40 Mcal/kg of ME and each diet was fed to the sows throughout a 28 day lactation. All diets provided a similar SID-lysine level （0.86%）. As a result, the diets provided a SID-Lys：ME ratio of 2.81, 2.72, 2.69, 2.65, 2.61 or 2.53 g/Mcal ME. Sow feed intake was significantly （P 〈 0.01） affected by the energy content of the diet as well as by sow parity. Using regression analysis, feed intake was shown to be maximized at 3.25, 3.21, 3.21 and 3.21 Mcal/kg of ME for parity 1, 2, 3＋ sows and the entire cohort of sows respectively （quadratic; P 〈 0.01）. In addition, the result of feed intake can be expressed as 2.65, 2.69, 2.69 and 2.68 g/Mcal based on analysis of SID-Lys：ME ratio. Litter weight gain was affected by dietary treatment for parity 3＋ sows and the entire cohort （P 〈 0.01）. Based on regression analysis, litter weight gain was maximized at 3.25 and 3.24 Mcal/kg of ME for parity 3＋ （quadratic; P 〈 0.01） and the entire cohort （quadratic; P 〈 0.01）. Similarly, the result of litter weight gain could be expressed as 2.65 and 2.66 g/Mcal of SID- Lys：ME ratio. Therefore, 3.25 Mcal/kg of ME was selected for Exp. 2 in which 150 sows （weighing 254.6 ± 7.3 kg and having an average parity of 3.4 ± 0.4） were allocated to one of five treatments in a completely randomized block design within parity （1, 2, and 3＋）. The experimental diets were formulated to contain 2.1, 2.4, 2.7, 3.0 or 3.3 g/Mcal of SID-Lys：ME ratio with all diets providing 3.25 Mcal/kg of ME. The diets were fed to the sows throughout a 28 day lactation. Sow body weight loss was affected by dietary treatment （parity 3＋ sows, P = 0.02; entire cohort, P 〈 0.01） and by sow parity （P 〈 0.01）. Litter weight at weaning and litter weight gain were affected by dietary treatment for parity 1, 2, 3＋ sows and the entire cohort （P 〈 0.01） as well as by sow parity （P 〈 0.01）. Plasma urea nitrogen （P 〈 0.01）, creatinine （P 〈 0.01） and non-esterifide fatty acids （P = 0.04） were decreased as the SID-Lys：ME ratio of the diet increased. Insulin-like growth factor-1 （P = 0.02）, estradiol （P 〈 0.01） and luteinizing hormone （P = 0.02） were increased as the SID-Lys：ME ratio in diet increased. Based on a broken-line model, the estimated SID-Lys： ME ratio to maximize litter weight gain was estimated to be 3.05 g/Mcal.

Development and validation of RP-HPLC and RP-UPLC methods for quantification of parathyroid hormones (1-34) in medicinal product formulated with meta-cresol

Rapid and sensitive reversed phase high performance liquid chromatography (RP-HPLC) and ultra performance liquid chromatography (RP-UPLC) method with UV detection has been developed and validated for quantification of parathyroid hormone (PTH) in presence of meta-cresol as a stabilizer in a pharmaceutical formulation.Chromatography was performed with mobile phase containing 0.1% Trifluoroacetic acid (TFA) in MilliQ water and 0.1% TFA in acetonitrile with gradient program and flow rate at 0.3 mL/min for HPLC and 0.4 mL/min for UPLC.Quantification was accomplished with internal reference standard (qualified against innovator product and National Institute for Biological Standards and Control (NIBSC) standard).The methods were validated for linearity (correlation coefficient 0.99),range,accuracy,precision and robustness.Robustness was confirmed by considering three factors;mobile phase composition,column temperature and flow rate/age of mobile phase.Intermediate precision was confirmed on different equipments,different columns and on different days.The relative standard deviation (RSD) (<2% for RP-HPLC and <1% for UPLC,n=30) indicated a good precision.Retention time was found about 17 min and 2 min by HPLC and UPLC methods,respectively.Both methods are simple,highly sensitive,precise and accurate and have the potential of being useful for routine quality control.

Variability of Serum Concentration of Calcium, Phosphate and Parathyroid Hormone Depending on Time of Blood Draw for Patients on Nocturnal Home Hemodialysis

Background: Guidelines for patients treated with conventional hemodialysis patients have been written for target serum levels for calcium (Ca), phosphate (PO4) and intact parathyroid hormone (iPTH). No guidelines exist for nocturnal home hemodialysis (NHHD) patients for target values or timing of the blood sample draw. We undertook a prospective cohort study to examine the variability in pre, post and clinic (post-post) serum values for Ca, PO4, and iPTH in NHHD patients to determine if timing of blood draw could affect clinical decisions. Methods: Twenty prevalent NHHD patients collected blood pre and post their usual NHHD session with an additional blood sample drawn in clinic (post-post). Median and interquartile range of pre, post and clinic (post-post) values of iPTH, PO4 and Ca were calculated and compared with Freidman/Wilcoxon test. Serum concentrations were also categorized according to Canadian Society of Nephrology (CSN) guidelines target values for pre and clinic (post-post) samples. The proportion of patients that would be categorized differently by clinic (post-post) samples was determined. Results: There was a significant difference between pre-serum values compared to post and clinic (post-post) values. Overall, iPTH, PO4 and Ca values would be misclassified in 25%, 70% and 50% respectively if blood was drawn at the clinic visit (post-post) compared to pre-HD as per CSN guidelines. Conclusions: Although no specific guideline has been written for NHHD patients, to ensure consistency of management compared to in-centre HD patients, lab values should be drawn pre-HD until clinical evidence suggests that the recommendations should be different for NHHD.

The effects of consumption of raw garlic on serum lipid level, blood sugar and a number of effective hormones on lipid and sugar metabolism in hyperglycemic and/or hyperlipidemic individuals ——Benefit of raw garlic consumption

Diabetes mellitus is one of the worldwide largest growing metabolic diseases. In this study the effects of consumption of raw garlic on serum lipid level, blood sugar and a number of effective hormones on lipid and sugar metabolism (thyroid hormones and insulin) in individuals either with high level of blood sugar or lipid were investigated. Eighty five volunteers having following clinical history enrolled in the study: Group 1: having blood sugar more than 126 mg/dl (30 vo-lunteers);Group 2: having cholesterol higher than 245 mg/dl (30 volunteers);Group 3: having blood sugar over 126 mg/dl and cholesterol more than 245 mg/dl (25 volunteers). In group 1, there wasn’t a sig-nificant differences between biochemical factors be-fore and after garlic consumption, whereas, in the second group after 6 weeks of garlic consumption a decline in cholesterol (P < 0.001), FBS and TG (P < 0.01) was observed but HDL-C (P < 0.001) was in-creased. Six weeks after termination of garlic con-sumption, cholesterol (P < 0.001), FBS and TG (P < 0.05) were in- creased and HDL-C (P < 0.01) was de-creased. In the third group, total cholesterol (P < 0.001), FBS (P < 0.01) and HbA1c decreased while HDL-C was in- creased. Other factors, including thy-roid hormones (T3, T4), TSH and insulin showed no significant alte- ration. In conclusion our results shown that raw garlic consumption can reduce the FBS and Lipid in hyperglycemic and/or hyperlipidemic individuals.

Recurrent acute pancreatitis as an initial presentation of primary hyperparathyroidism:A case report

BACKGROUND With 4.9 to 35 instances per 100000 cases,hyperparathyroidism is one of the rarest causes of acute pancreatitis.The major cause of primary hyperparathyroidism is a parathyroid adenoma,which can manifest clinically in various ways.CASE SUMMARY We discuss the unusual case of a 13-year-old boy with recurrent pancreatitis as the initial presentation of primary hyperparathyroidism.The cause of his recurrent pancreatitis remained unknown,and the patient had multiple admissions with acute pancreatitis over 3 years.His diagnosis was delayed due to the initial normal levels of parathyroid hormone,which were later reported elevated in a subsequent episode where ultrasound neck and thyroid scintigraphy revealed a parathyroid adenoma as the underlying cause.After the diagnosis was made,he underwent surgical resection of the adenoma.CONCLUSION This case study stresses the importance of considering uncommon causes for recurrent pancreatitis.

Alteration of Sex and Non-Sex Hormones and Distribution Features of Blood ABO System Groups among the Women with Uterine Body Tumors

Objectives: The aim of the investigation was to study the hormonal status (sex hormones: estradiol (E2), progesterone (P), testosterone (T);non-sex gonadotropic hormones-luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) of women with benign and malignant tumors of uterine body in the reproductive, menopause and postmenopause periods. Also the distribution features of the blood ABO system phenotype groups and their link to the development of uterine body tumors have been studied. Methods: The determination of hormones was made by the enzyme analysis method (ELAIZA), provided by the proper ELAIZA kits. For the study of blood ABO system antigens, internationally recognized immunoserology methods were used. Results: Investigations revealed the increased level of E2 and T on the background of the reduced P in the blood of the women with uterine tumors in the reproductive, menopause and post-menopause period. As for gonadotropic hormones, the decreased levels of LH and FSH have also been detected. From the ABO system phenotype groups A(II) group had the highest frequency between the women with malignant uterine tumor in the reproductive age. O (I) phenotype group was the most frequent in case of menopause and post-menopause women with uterine malignant tumors. Conclusions: Hormonal imbalance creates good conditions for the proliferation of uterine tissues and hence causes the development of benign and malignant uterine tumors. The imbalance of the sex steroid and gonadotropic hormones in the blood of post-menopause women indicates on the genotoxic mechanism of cancer development on the background of age-related changes. A(II) group had the highest frequency between the reproductive age women with uterine malignant tumor, while O (I) group was the most frequent in case of menopause and post-menopause patients.

The Effect of Glucose Added to the Dialysis Fluid on Blood Pressure, Vasoactive Hormones and Energy Transfer during Hemodialysis in Chronic Renal Failure

Background: Previous studies showed that blood pressure was reduced in patients with chronic renal failure during hemodialysis with glucose added to the dialysis fluid. We wanted to test the hypotheses that blood pressure is reduced in non-diabetic and diabetic dialysis patients, when glucose is added to the dialysis fluid, and that blood pressure changes are caused by changes in plasma concentrations of vasoactive hormones or to vasodilation secondary to an increase in body temperature. Methods: The effect of dialysis with glucose added to the dialysis fluid was measured in three randomized, placebo-controlled, un-blinded and cross-over studies with periods of one week duration. In non-diabetic nephropathy (Study 1, n = 19) and diabetic nephropathy (Study 2, n = 15), we measured blood pressure (BP) and pulse rate (PR), plasma concentrations of glucose (p-Glucose), renin (PRC), angiotensin II (p-AngII), endothelin (p-Endot), insulin (p-Ins), glucagon (p-Glu), and human growth hormone (p-hGH). In non-diabetic nephropathy (Study 3, n = 24), we measured the effect of dialysis with glucose added to the dialysis fluid on energy transport from form the body using body temperature control. Results: Study 1 and 2 showed that BP, PRC, p-AngII, and p-Ins were unchanged, whereas P-Endot increased and P-hGH decreased, in dialysis patients with or without glucose added to the dialysis fluid. In diabetics, a marginal increase in p-Glu was measured during dialysis with glucose, but not without glucose. Study 3 showed that SBP increased significantly using dialysis with temperature control of dialysis fluid compared with no temperature control (145 versus 138 mm Hg). In parallel with the increase in SBP, the energy flux from the patients was significantly higher with temperature control than without. Conclusion: In non-diabetics and diabetics, blood pressure was unchanged during dialysis with glucose added to the dialysis fluid in a short-term study. Vasoactive hormones in plasma were changed in the same way independently of glucose in the dialysis fluid. Systolic blood pressure increased using dialysis with temperature control of dialysis fluid, presumably due to vasoconstriction to prevent or antagonize a fall in body temperature.

A study of effects of using low dialysate calcium concentration (1.50 mmol/L) on blood pressure,serum concentrations of calcium,parathyroid hormone and aldosterone in chronic hemodialysis patients

Background: Dialysis centres around the world use different concentrations of calcium in dialysate solution,ranging from 1. 25 to 1. 75 mmol / L. However,a dialysate concentration of 1. 25 mmol / L is recommended. [1] Higher or lower dialysate calcium concentrations are indicated in patients,depending on their co-morbid factors. We explored the effects of using a calcium dialysate solution of 1. 50 mmol / L compared to a 1. 75 mmol / L calcium dialysate solution on the Blood Pressure (BP) ,serum concentrations of Calcium,Parathyroid Hormone (PTH) and Aldosterone in chronic hemodialysis (HD) patients. Method: 42 patients were enrolled in the study. First a 1. 50 mmol / L low calcium dialysate solution (LCDS) was used for 4 hour dialysis,and for the next session of HD,a 1. 75 mmol / L (NCDS) normal calcium dialysate solution was used. Blood pressure was measured at 5 intervals of time: pre HD,at 60,120,180 and 240 minutes into the HD session. Pre and post HD blood samples were taken for serum calcium,PTH and Aldosterone levels. Results: All 42 patients completed the study. With LCDS,the post HD serum calcium levels were (2. 51 ± 0. 14) mmol / L,compared to (2. 85 ± 0. 17) mmol / L for NCDS (P < 0. 01) . A post HD serum PTH level of (80. 6 ± 144. 93) pg / ml was observed when using LCDS,whereas a (52. 25 ± 115. 89) pg / ml serum PTH level was noted with NCDS (P < 0. 01) . As for aldosterone,a post HD value of (161. 77 ± 80. 42) ng / L was obtained with LCDS and (165. 50 ± 78. 84) ng / L with NCDS (P < 0. 01) . The mean post HD systolic blood pressure was (129. 17 ± 25. 42) mmHg with LCDS dialysis compared to (132. 50 ± 20. 32) mmHg for NCDS dialysis (P < 0. 01) and the diastolic BP values observed were (75. 10 ±10. 34) mmHg and (78. 26 ±11. 63) mm Hg(P <0. 01) ,respectively. Conclusion: LCDS can more effectively improve hypercalcemic status in dialysis patients than NCDS. Using LCDS stimulates the secretion of PTH more than when using NCDS. LCDS decreases aldosterone levels more than NCDS. Patients undergoing dialysis with LCDS have a lower post dialysis BP compared to those using NCDS. LCDS has a greater effect in decreasing both the post systolic and diastolic blood pressure than NCDS. Serum calcium,PTH and aldosterone levels have a greater decreasing effect on BP in LCDS than NCDS. Dialysate calcium profiling might be used as a means of therapy to control hypercalcemia, especially in patients who are hemodynamically stable.

Comparison between recombinant human parathyroid hormone(1-34) and elcatonin in treatment of primary osteoporosis

Objective:To evaluate the efficacy and safety of rhPTH(1-34) vs.elcatonin.Methods:Sixty palients with primary OP were randomly divided into two groups according to the ratio of 3:1.rhPTH(1-34) group(PTH group) was treated with subcutaneous injection of rhPTH(1-34) 20 μg daily for 18 months,and the elcalonin group(CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months.Bone mineral density(BMD) of the lumbar spine 2-4(L_(2-4))and femoral neck,serum calcium and phosphorus,urinary calcium,serum hone specific alkaline phosphatase(BSAP).and urinary c-terminal telopeptides of type Ⅰ collagen/creatinine(uCTX-Ⅰ /Cn were tested at baseline,and 6.12.and 18 months after treatment.Results:In PTH group.HMD of L_(2-4),at 6,12.and 18 months,BDM of Femoral neck at 18 month,BSAP at 6 and 12 months and uCTX- Ⅰ /Cr at 6.12 and 18 months were all significantly raised.In CT group.HMD of L_(2-4) at12 month and that of femoral neck at 12 and 18 months were significantly elevated,while HSAP was significantly decreased at 12 and 18 months,and no significant difference on CTX- Ⅰ /Cr was observed.When BMD growth and growth rate between two groups were compared.PTH group had better improvement in L_(2-4) BMD and growth rate than CT group at 6.12.and 18 months.BMD growth and growth rale of femoral neck al 12 month and its growth at 18 month in CT group were higher than in PTH group,hut there was no significant difference between two groups regarding the growth rates at 18 month.Besides,there were no significant differences regarding the rales ol adverse reactions between two groups.Conclusions:rhPTH(1—34),is safe and effective in the treatment of primary OP.It is superior to elcatonin in improving vertebral HMD at onset time,growth rate and growth range,but inferior to elcatonin at HMD of femoral neck.

Osteoporotic fracture and parathyroid hormone

Osteoporosis and age-related bone loss is associated with changes in bone remodeling characterized by decreased bone formation relative to bone resorption,resulting in bone fragility and increased risk of fractures.Stimulating the function of bone-forming osteoblasts,is the preferred pharmacological intervention for osteoporosis.Recombinant parathyroid hormone(PTH),PTH(1-34),is an anabolic agent with proven benefits to bone strength and has been characterized as a potential therapy for skeletal repair.In spite of PTH’s clinical use,safety is a major consideration for long-term treatment.Studies have demonstrated that intermittent PTH treatment enhances and accelerates the skeletal repair process via a number of mechanisms.Recent research into the molecular mechanism of PTH action on bone tissue has led to the development of PTH analogs to control osteoporotic fractures.This review summarizes a number of advances made in the field of PTH and bone fracture to combat these injuries in humans and in animal models.The ultimate goal of providing an alternative to PTH,currently the sole anabolic therapy in clinical use,to promote bone formation and improve bone strength in the aging population is yet to be achieved.

Effects of Environmental Lead Pollution on Blood Lead and Sex Hormone Levels among Occupationally Exposed Group in An E-waste Dismantling Area

Objective To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. Methods An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. Results The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 I~/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. Conclusion There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks.

Safety,Tolerability and Pharmacokinetic Study of Recombinant Human Parathyroid Hormone [rhPTH(1-84)] in Chinese Healthy Volunteers

The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH （1-84）] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH （1-84） subcutaneously： 1, 2, and 4 μg/kg. The blood was timing drawn and the serum concentration of rhPTH （1-84） was determined by enzyme linked immunosorbent assay （ELISA）. Serum concentration-time curves of PTH （1-84） exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration. Serum terminal half-time of PTH （1-84） was approximately 2 h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean Cmax and AUC0_24 ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg.h.mL^-1 over the dose range. The drug was well tolerated, the clinical symptoms were generally mild and of short duration.

Gastric emptying and plasma levels of gastrointestinal hormones in patients with peptic ulcer

IM To study the plasma level of gastrointestinal hormones and gastric emptying in patients with peptic ulcer. METHODS Thirty patients with gastric ulcer (GU), and 29 duodenal ulcer (DU) and 12 controls were studied. Plasma levels of SS, VIP and SP were measured by radioimmunoassay, and gastric emptying half time (GET1/2) was determined with TC99mresin solid meal method. RESULTS GET1/2(min) was significantly longer in GU than that in controls (659±148 vs 533±43, P<001) and plasma VIP levels (ng/L) were significantly higher than in controls (375±107 vs 184±59, P<005). There was a significant positive correlation between GET1/2 and plasma VIP levels (r=055,P<001). No significant changes were found in SS and SP in GU compared with controls (P>005). GET1/2 in DU was markedly shorter than the control group (417±102 vs 533±43, P<001), and plasma SS levels (ng/L) significantly lower than those in controls (64±25 vs 119±34,P<001), there was a significant positive correlation between GET1/2 and SS levels (r=056,P<001). Plasma SP levels (ng/L) in DU were significantly higher than the controls (544±127 vs 416±58,P<001),there was a significant negative correlation between GET1/2 and SP levels (r=-068,P<001). No significant difference was found in the plasma VIP levels between DU and controls (P>005).CONCLUSION VIP elevation may contribute to the GET1/2 delay and the occurrence of GU. The increased SP and lowered SS may play important roles in the GET1/2 acceleration and the pathogensis of DU.

Impact of parathyroid hormone on bone marrow-derived stem cell mobilization and migration

Parathyroid hormone(PTH) is well-known as the principal regulator of calcium homeostasis in the human body and controls bone metabolism via actions on the survival and activation of osteoblasts. The intermittent administration of PTH has been shown to stimulate bone production in mice and men and therefore PTH administration has been recently approved for the treatment of osteoporosis. Besides to its physiological role in bone remodelling PTH has been demonstrated to influence and expand the bone marrow stem cell niche where hematopoietic stem cells, capable of both self-renewal and differentiation, reside. Moreover, intermittent PTH treatment is capable to induce mobilization of progenitor cells from the bone marrow into the bloodstream. This novel function of PTH on modulating the activity of the stem cell niche in the bone marrow as well as on mobilization and regeneration of bone marrow-derived stem cells offers new therapeutic options in bone marrow and stem cell transplantation as well as in the field of ischemic disorders.

Environmental mercury exposure, semen quality and reproductive hormones in Greenlandic Inuit and European men： a cross-sectional study

Several animal studies indicate that mercury is a male reproductive toxicant, but human studies are few and contradictory. We examined semen characteristics and serum levels of reproductive hormones in relation to environmental exposure to mercury. Blood and semen samples were collected from 529 male partners of pregnant women living in Greenland, Poland and Ukraine between May 2002 and February 2004. The median concentration of the total content of mercury in whole blood was 9.2 ng ml-1 in Greenland （0.2- 385.8 ng ml-1）, 1.0 ng m1-1 in Poland （0.2-6.4 ng ml-z） and 1.0 ng ml-I in Ukraine （0.2-4.9 ng ml-1）. We found a significantly positive association between the blood levels of mercury and serum concentration of inhibin B in men from Greenland （p=0.074, 95% confidence interval （CI）=0.021 to 0.126） and in an analysis including men from all three regions （p=0.067, 95% C1=0.024 to O. 110）. The association may be due to beneficial effects of polyunsaturated fatty acids （PUFAs）, which are contained in seafood and fish. No significant association （P〉O.05） was found between blood concentrations of mercury and any of the other measured semen characteristics （semen volume, total sperm count, sperm concentration, morphology and motility） and reproductive hormones （free androgen index {FAI）, follicle-stimulating hormone （FSH）, luteinizing hormone （LH）, testosterone and LH xtestosterone） in any region. In conclusion, the findings do not provide evidence that environmental mercury exposure in Greenlandic and European men with median whole blood concentration up to 10 ng m1^-1 has adverse effects on biomarkers of male reproductive health.

Hypoxia-inducible factor-1a restricts the anabolic actions of parathyroid hormone

The hypoxia inducible factors （Hifs） are evolutionarily conserved transcriptional factors that control homeostatic responses to low oxygen. In developing bone, Hif-1 generated signals induce angiogenesis necessary for osteoblast specification, but in mature bone, loss of Hif-1 in osteoblasts resulted in a more rapid accumulation of bone. These findings suggested that Hif-1 exerts distinct developmental functions and acts as a negative regulator of bone formation. To investigate the function of Hif-1a in osteoanabolic signaling, we assessed the effect of Hif-1a loss-of-function on bone formation in response to intermittent parathyroid hormone （PTH）. Mice lacking Hif-1a in osteoblasts and osteocytes form more bone in response to PTH, likely through a larger increase in osteoblast activity and increased sensitivity to the hormone. Consistent with this effect, exposure of primary mouse osteoblasts to PTH resulted in the rapid induction of Hif-1a protein levels via a post-transcriptional mechanism. The enhanced anabolic response appears to result from the removal of Hif-1a-mediated suppression of β-catenin transcriptional activity. Together, these data indicate that Hif-1a functions in the mature skeleton to restrict osteoanabolic signaling. The availability of pharmacological agents that reduce Hif-1a function suggests the value in further exploration of this pathway to optimize the therapeutic benefits of PTH.

Effect of parathyroid hormone on apoptosis of human medullary thyroid carcinoma cells

Objective The aim of the study was to investigate the effect of parathyroid hormone(PTH) on the apoptosis of human medullary thyroid carcinoma(MTC) cells.Methods In vitro cultured medullary thyroid carcinoma cell lines were treated with parathyroid hormone and parathyroid hormone receptor-monoclonal antibody,and the apoptosis of cells was detected by flow cytometry.Results The cell morphology changed significantly after treatment based on the observation using the inverted phase-contrast microscope.Various concentrations of parathyroid hormone and parathyroid hormone receptor-monoclonal antibody effectively induced apoptosis in a time-and concentrationdependent manner.When the concentration of parathyroid hormone was 2.0 μmol/L and that of parathyroid hormone receptor-monoclonal antibody was 1.0 μmol/L,the apoptotic rate was 13.24% and 20.78%,respectively,representing a statistically significant difference from that of the control cells(P < 0.05).Conclusion PTH plays a role in inducing apoptosis of human MTC cells.

Parathyroid hormone pulsatility: physiological and clinical aspects

Parathyroid hormone （PTH） secretion is characterized by an ultradian rhythm with tonic and pulsatile components. In healthy subjects, the majority of PTH is secreted in tonic fashion, whereas approximately 30% is secreted in low-amplitude and high-frequency bursts occurring every 10-20 min, superimposed on tonic secretion. Changes in the ultradian PTH secretion were shown to occur in patients with primary and secondary osteoporosis, with skeletal effects depending on the reciprocal modifications of pulsatile and tonic components. Indeed, pathophysiology of spontaneous PTH secretion remains an area potentially suitable to be explored, particularly in those conditions such as secondary forms of osteoporosis, in which conventional biochemical and densitometric parameters may not always give reliable diagnostic and therapeutic indications. This review will highlight the literature data supporting the hypothesis that changes of ultradian PTH secretion may be correlated with skeletal fragility in primary and secondary osteoporosis.