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.

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.

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.

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.

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.

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.

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.

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.

Inhibition effects of parathyroid hormone on human medullary thyroid carcinoma cells

Objective： The purpose of the study was to investigate the effects of parathyroid hormone and parathyroid hormone receptor monoclonal antibody on in vitro growth and proliferation of human medullary thyroid carcinoma cell lines. Methods： The medullary thyroid carcinoma cell line was cultured in vitro, with parathyroid hormone and parathyroid hormone receptor monoclonal antibody treatment intervention, the growth of the cells was observed under an inverted contrast micro scope, the MTT assay was used to detect the cell growth inhibition rate. Results： Under the inverted contrast microscope, the cells changed significantly, the parathyroid hormone and parathyroid hormone receptor monoclonal antibodies can effectively inhibit the proliferation of medullary thyroid cancer cells in a time and dose dependent. When parathyroid hormone concentra tion reached a concentration of 2.0 IJmol/L, the parathyroid hormone receptor monoclonal antibody reached a concentration of 1.0 μmol/L, the cell growth was most significantly inhibited （P 〈 0.05）. Conclusion： Parathyroid hormone and parathyroid hormone receptor monoclonal antibody were able to inhibit the proliferation of medullary thyroid carcinoma cells and signifi cantly reduce the proliferation index.

Vitamin D and Parathyroid Hormone Profiles in Living Kidney Failure Patients in Côte d’Ivoire

Introduction: Abnormalities in mineral and bone metabolism, particularly phosphocalcic metabolism, are common in renal failure and are associated with a significant morbidity and mortality. The regulation of phosphocalcic metabolism is subject to a particularly precise and complex control of parathormone (PTH) and vitamin D. Assessment of vitamin D and parathyroid hormone concentrations would help to improve the medical management of patients with chronic kidney disease and ensure a better quality of life. Methods: The study population consisted of 138 individuals including 46 non- dialysis renal failure patients, 46 chronic hemodialysis patients and 46 non- renal failure volunteers to serve as controls. Serum Parathyroid hormone and Vitamin D concentrations were measured using the Vidas automated system. Results: 25-hydroxyvitamin D concentrations in controls (65 ± 2.41 nmol/L) and dialysis patients (70 ± 3.03 nmol/L) were significantly higher than those in CKD patients (48 ± 3.34 nmol/L). On the other hand, the mean values of Parathyroid hormone in dialysis patients (312 ± 36.22 pg/mL) and CKD patients (117 ± 10.68 pg/mL) were very high compared to that in controls (25 ± 2.34 pg/mL). Conclusion: Secondary hyperparathyroidism is common in renal failure. Parathyroid hormone and 25-hydroxyvitamin D assays would be adequate for better management of chronic renal failure.

Alcohol-induced Wnt signaling inhibition during bone fracture healing is normalized by intermittent parathyroid hormone treatment

Nearly half of orthopaedic trauma patients are intoxicated at the time of injury, and excess alcohol consumption increases the risk for fracture nonunion. Previous studies show alcohol disrupts fracture associated Wnt signaling required for normal bone fracture repair. Intermittent parathyroid hormone(PTH) promotes bone growth through canonical Wnt signaling, however, no studies have investigated the effect of PTH on alcohol-inhibited bone fracture repair. Male C57 BL/6 mice received two-3 day alcohol binges separated by 4 days before receiving a mid-shaft tibia fracture. Postoperatively, mice received PTH daily until euthanasia. Wnt/β-catenin signaling was analyzed at 9 days post-fracture. As previously observed, acute alcohol exposure resulted in a >2-fold decrease in total and the active form of β-catenin and a 2-fold increase in inactive β-catenin within the fracture callus. Intermittent PTH abrogated the effect of alcohol on β-catenin within the fracture callus. Upstream of β-catenin, alcohol-treated animals had a 2-fold decrease in total LRP6, the Wnt co-receptor, which was restored with PTH treatment. Alcohol nor PTH had any significant effect on GSK-3β. These data show that intermittent PTH following a tibia fracture restores normal expression of Wnt signaling proteins within the fracture callus of alcohol-treated mice.

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.

Feeding Reduces Serum Concentration of Endogenous Bioactive (1-84), but Not Total Intact Parathyroid Hormone in Female Sprague-Dawley Rats

Background: Interpretation of parathyroid hormone (PTH) measurements requires an understanding of its structural conformation. PTH reflects calcium intake and vitamin D status but is commonly measured in the fasted state using 2nd generation assays, known to cross-react with PTH 7-84 fragments, which is not observed with 3rd generation assays. The objective was to determine if plasma PTH in the fed and non-fed state differ while controlling for diurnal rhythm and the generation of PTH assay. Methods: Blood was sampled, 2 d apart, from Sprague-Dawley rats (30 males and 30 females) in both fed and non-fed states at 20 wk of age (weight: 470.2 ± 23.2 g) for measurement of ionized calcium (iCa), total intact (INT) and bioactive 1-84 (BIO) PTH. Differences between groups were tested using a GLIMMIX model with sex and feeding state as fixed effects and individual rats as a random effect. Results: Females had a lower iCa than males (F: 1.43 ± 0.01 vs M: 1.46 ± 0.01 mmol/L, P = 0.03). In males and females, there was no difference between fed and non-fed groups when PTH was assessed using the INT PTH assay (M Fed: 21.6 ± 1.3 vs M Non-fed: 22.6 ± 2.3 pmol/L, P = 0.59;F Fed: 19.3 ± 1.5 vs F Non-fed: 22.8 ± 2.9 pmol/L, P = 0.39). However, in females only, PTH measured using the BIO PTH, was significantly lower in the fed group versus the non-fed (Fed: 8.4 ± 0.8 vs Non-fed: 16.7 ± 3.4 pmol/L, P = 0.05). Conclusions:

The Relationship of Serum Calcium, Phosphorus, and Parathyroid Hormone with Renal Function in Elderly Osteoporotic Patients with No History of Chronic Kidney Disease

The prevalence of osteoporosis and decline in renal function increases with age. Therefore, the coexistence rate of both these conditions rises in the elderly population. Abnormalities in mineral bone metabolism are major complications in chronic kidney disease (CKD). However, in elderly osteoporotic patients without a history of CKD, there are few reports on the relationship between calcium (Ca), phosphorus (P), and parathyroid hormone (PTH), and renal function. The purpose of this study was to investigate the relationship between Ca, P, and PTH, and renal function in elderly osteoporosis patients with no history of CKD. We evaluated 169 patients who had been treated for osteoporosis. The eGFR decreased with age resulting in a negative correlation (r = -0.514, p p p p p < 0.01, respectively). Even if Ca and P are in the normal range, in case of a poor effect of an osteoporotic therapeutic drug, it is necessary to consider the measurement of intact PTH in elderly osteoporosis patients with no history of CKD.

Parathyroid Hormone: Is It Really the Cause for Increased Tooth Mobility after Orthognathic Surgery?

Introduction: Following orthognathic surgery, increased tooth mobility is observed clinically and is utilized for postsurgical orthodontic tooth movement. It was suggested that the increase may result from a surgery-associated alteration of parathyroid hormone (PTH) and calcium metabolism. Materials and Methods: 30 young adult patients were divided into a mandibular osteotomy group (Group A, n = 20) and an untreated control group (Group B, n = 10). Tooth mobility was evaluated using the Periotest device. Tooth mobility, serum PTH and calcium levels were determined repeatedly for both groups. Results: The tooth mobility was increased significantly in the Group A patients in the first 10 days post-surgery. All serum PTH and calcium mean levels were within normal ranges. No significant differences were found between the measurements of both groups. The serum calcium levels recorded at the 1st post-surgery day were slightly lower in the operated patients compared to the control group. Conclusion: It can be concluded that the increased facility of orthodontic tooth movement immediately post-surgery was confirmed by Periotest measurements, while no association was found with surgery-related altered levels of PTH and calcium. Since dietary effects can be ruled out, the increase of clinical tooth mobility may rather result from preoperative orthodontic forces and/or the post-surgical elimination of masticatory muscular influences.

ASSOCIATION OF PARATHYROID HORMONE GENE POLYMORPHISM WITH BONE MINERAL DENSITY IN CHINESE WOMEN

Objective.To investigate the distribution frequency of parathyroid hormone(PTH)gene polymorphism in healthy adults from Bejing area and to explore the association of PTH genotypes with bone mineral density(BMD).Methods.PTH gene polymorphism was detected in270subjects by polymerase chain reaction(PCR)and PCR /restriction fragment length polymorphism(PCR /RFLP).The digestion products of restriction enzyme Bst B1were separated on1%agarose gels.PTH genotypes were confirmed by DNA sequences analysis.BMD was measured by dual-energy X-ray absorptiometry(DEXA,DPX -L ,Lunar).Results.Genotype frequencies of BB,Bb,bb were73.7%,25.9%and0.4%respectively in Beijing adults(P<0.01),67.1%,32.2%and0.7%in postmenopausal women,which was different from Japanese wom-en.We statistically compared bone mineral density at the lumbar2-4and proximal femur between BB and Bb genotypes.No obvious association was found between the BMD and PTH genotypes in Beijing women(P>0.05).Conclusion.PTH gene polymorphism is not associated with BMD in Chinese women.The further research to explore the genetic risk factors of osteoporosis should be committed.

Dose-dependent effect of parathyroid hormone 1-34 fragment and its influence mechanism on the functional activity of isolated heart

The present investigation is the continuation of our prior clinical studies on the content of parathyroid hormone (PTH), its paracrine analog, parathyroid hormone-related protein (PTHrP) and electrolytes in blood of patients with heart failure. The results of these studies formed the basis for the nomination of the hypothesis on PTH and PTHrP compensatory-modulating effect on the contractile activity of heart. The objective of this study is to elucidate the mechanism of the compensatory-modulating effect of PTH on heart functional activity, which is realized by the study of effective doses of PTH by pharmacological analysis, using different inhibitors. The dose-dependent effect of PTH on the heart contraction rate and amplitude is studied on the frog isolated heart by the method of non-invasive registration of heart contractile activity. The method is based on the photoelectric principle of the reflected from the contractile object light ray transformation into an electric signaling. It is shown that the most effective dose that has positive chronotropic and inotropic effects on heart is 10–10 M hormone. To clarify the mechanism of PTH physiological dose action on the contractile activity of heart PTH 1-34 is combined with Ca-channel as well as phosphodiesterase blockers. The mentioned substances are applied based on the fact that PTH effect on target cells is mediated by secondary messengers, particularly calcium ions and cAMP. Based on the data obtained by combination of hormone with Verapamil (10–5 M) and Theophylline (10–4 M), we concluded on the involvement of calcium ions in the realization of chronotropic and cAMP in the inotropic effects on the heart.