Vandetanib Tumor Shrinkage in Metastatic Medullary Thyroid Cancer Allowing Surgical Resection of the Primary Site: A Case Report.

Vandetanib has been shown to improve progression-free survival in adults with advanced medullary thyroid cancer. This article describes a pediatric patient with metastatic medullary thyroid cancer secondary to sporadic multiple endocrine neoplasia 2B, treated with vandetanib. At presentation, he had an inoperable primary tumor, with carotid encasement, and pulmonary metastases. Vandetanib induced a significant response: calcitonin and carcinoembryonic antigen levels both fell considerably, primary tumor maximal diameter decreased by 68%, and pulmonary metastases became no longer detectable. This allowed surgical resection of the primary tumor. The patient remains well after over 6 years of vandetanib therapy, with no treatment toxicity.

The Determination of Procalcitonin Concentration in Early-Onset Neonatal Infection.

The aim of this study was to assess the clinical usefulness of blood procalcitonin (PCT) levels for the diagnosis and therapeutic monitoring of early-onset neonatal sepsis (EONS). PCT as well as C-reactive protein (CRP) levels and white blood cell (WBC) count were measured in venous blood from 57 infected and 72 uninfected neonates. Differences between groups for PCT, CRP, and WBC levels were significant. The threshold value on the receiver operating characteristic curve in the prediction of EONS was 5.33 ng/mL for PCT, 9.3 mg/L for CRP, and 14.9 × 109/L for WBC. There was no effect of antibiotic administered to the mother on PCT, CRP, and WBC levels in neonatal blood sampled before treatment of EONS. Evidently reduced PCT levels are observed after 2 days of treatment. The authors conclude that prenatal antibiotic therapy does not reduce the value of PCT levels in blood for the diagnosis of EONS.

Early procalcitonin kinetics and appropriateness of empirical antimicrobial therapy in critically ill patients: A prospective observational study.

PURPOSE: The purpose was to investigate the value of procalcitonin (PCT) kinetics in predicting the appropriateness of empirical antimicrobial treatment in critically ill patients. MATERIALS AND METHODS: This prospective observational study recruited patients in whom empirical antimicrobial therapy was started for suspected infection. Biochemical and physiological parameters were measured before initiating antimicrobials (t0), 8 hourly (t8, t16, t24), and then daily (day2-6). Patients were grouped post hoc into appropriate (A) and inappropriate (IA) groups. RESULTS: Of 209 patients, infection was confirmed in 67%. Procalcitonin kinetics were different between the IA (n = 33) and A groups (n = 108). In the IA group, PCT levels (median [interquartile range]) increased: t0= 2.8 (1.2-7.4), t16= 8.6 (4.8-22.1), t24= 14.5 (4.9-36.1), P< .05. In the A group, PCT peaked at t16 and started to decrease by t24: t0= 4.2 (1.9-12.8), t16= 6.99 (3.4-29.1), t24= 5.2 (2.0-16.7), P< .05. Receiver operating characteristic analysis revealed that a PCT elevation greater than or equal to 69% from t0 to t16 had an area under the curve for predicting inappropriate antimicrobial treatment of 0.73 (95% confidence interval, 0.63-0.83), P< .001; from t0 to t24, a greater than or equal to 74% increase had an area under the curve of 0.86 (0.77-0.94), P< .001. Hospital mortality was 37% in the A group and 61% in the IA group (P= .017). CONCLUSIONS: Early response of PCT in the first 24 hours of commencing empirical antimicrobials in critically ill patients may help the clinician to evaluate the appropriateness of therapy.

Effects of Dulaglutide on Thyroid C Cells and Serum Calcitonin in Male Monkeys.

Glucagon-like peptide-1 (GLP-1) receptor agonists, used for the treatment of type 2 diabetes, have caused hyperplasia/neoplasia of thyroid C cells in rodent carcinogenicity studies. Studies in monkeys have not identified an effect of GLP-1 receptor agonists on thyroid C cells; however, group sizes were small. Dulaglutide is a once-weekly, long-acting human GLP-1 receptor agonist recently approved in the United States and the European Union. The objective of this study was to determine whether dulaglutide altered C-cell mass in monkeys. Male cynomolgus monkeys (20 per group) were sc injected with dulaglutide 8.15 mg/kg (∼500-fold maximum human plasma exposure) or a vehicle control twice weekly for 52 weeks. Basal and calcium gluconate-stimulated serum calcitonin concentrations were obtained at 3, 6, 9, and 12 months. Thyroid glands were weighed, fixed, and sectioned at 500-µm intervals. C-cell volumes were measured using an automated image analysis. C-cell proliferation was estimated using Ki67/calcitonin colabeling and cell counting. Administration of dulaglutide 8.15 mg/kg twice weekly for 52 weeks did not increase serum calcitonin in monkeys or affect thyroid weight, histology, C-cell proliferation, or absolute/relative C-cell volume. This study represents a comprehensive evaluation of the monkey thyroid C cells after dosing with a GLP-1 receptor agonist, with a large group size, and measurement of multiple relevant parameters. The lack of effect of dulaglutide on C cells is consistent with other studies in monkeys using GLP-1 receptor agonists and suggests that nonhuman primates are less sensitive than rodents to the induction of proliferative changes in thyroid C cells by GLP-1 receptor agonists.

Chronic Toxicity and Carcinogenicity Studies of the Long-Acting GLP-1 Receptor Agonist Dulaglutide in Rodents.

The tumorigenic potential of dulaglutide was evaluated in rats and transgenic mice. Rats were injected sc twice weekly for 93 weeks with dulaglutide 0, 0.05, 0.5, 1.5, or 5 mg/kg corresponding to 0, 0.5, 7, 20, and 58 times, respectively, the maximum recommended human dose based on plasma area under the curve. Transgenic mice were dosed sc twice weekly with dulaglutide 0, 0.3, 1, or 3 mg/kg for 26 weeks. Dulaglutide effects were limited to the thyroid C-cells. In rats, diffuse C-cell hyperplasia and adenomas were statistically increased at 0.5 mg/kg or greater (P ≤ .01 at 5 mg/kg), and C-cell carcinomas were numerically increased at 5 mg/kg. Focal C-cell hyperplasia was higher compared with controls in females given 0.5, 1.5, and 5 mg/kg. In transgenic mice, no dulaglutide-related C-cell hyperplasia or neoplasia was observed at any dose; however, minimal cytoplasmic hypertrophy of C cells was observed in all dulaglutide groups. Systemic exposures decreased over time in mice, possibly due to an antidrug antibody response. In a 52-week study designed to quantitate C-cell mass and plasma calcitonin responses, rats received twice-weekly sc injections of dulaglutide 0 or 5 mg/kg. Dulaglutide increased focal C-cell hyperplasia; however, quantitative increases in C-cell mass did not occur. Consistent with the lack of morphometric changes in C-cell mass, dulaglutide did not affect the incidence of diffuse C-cell hyperplasia or basal or calcium-stimulated plasma calcitonin, suggesting that diffuse increases in C-cell mass did not occur during the initial 52 weeks of the rat carcinogenicity study.

Effect of oral N-acetylcysteine treatment on immune system in continuous ambulatory peritoneal dialysis patients.

AIM: to determine the effect of oral N-acetylcysteine (NAC) on plasma levels of inflammatory markers in Continuous Ambulatory Peritoneal Dialysis (CAPD) patients. METHODS: we performed a placebo-controlled study over 8 weeks in 32 patients on regular CAPD. The patients were divided into 2 groups of 16 patients matched for age and gender. The first group was given NAC 2x600 mg/day for 8 weeks and inflammatory parameter was compared with control group. The immune system is determined from the average levels of Procalcitonin, IL-6, IL-1, C3, SICAM, hsCRP, and TNF- before and after treatment with NAC. Student t-test was performed to compare the means between NAC receiving and control groups. All statistics were done using SPSS software (SPSS Ver 16.0). RESULTS: administration of NAC, significantly diminished PCT (-0.38±0.57 vs 0.09±0.14; p=0.004), IL-6 (-1.94±3.03 vs 1.19±1.99; p=0.002), IL-1 (-0.14±0.21 vs 0.01±0.04; p=0.010), C3 (-7.40±12.04 vs 4.60±8.12; p=0.002), sICAM (-80.59±29.18 vs -35.02±46.99; p=0.007), hsCRP (-1.50±1.32 vs 0.81±1.17; p<0.001) and TNF- (-0.73±0.47 vs 0.14±0.74; p<0.001) levels compared control to group. CONCLUSION: short-term oral NAC treatment resulted in reduction of circulating PCT, IL-6, IL-1, C3, sICAM, hsCRP, and TNF- in CAPD patients.

The relevance of preclinical research models for the development of antimigraine drugs: focus on 5-HT(1B/1D) and CGRP receptors.

Migraine is a complex neurovascular syndrome, causing a unilateral pulsating headache with accompanying symptoms. The past four decades have contributed immensely to our present understanding of migraine pathophysiology and have led to the introduction of specific antimigraine therapies, much to the relief of migraineurs. Pathophysiological factors culminating into migraine headaches have not yet been completely deciphered and, thus, pose an additional challenge for preclinical research in the absence of any direct experimental marker. Migraine provocation experiments in humans use a head-score to evaluate migraine, as articulated by the volunteer, which cannot be applied to laboratory animals. Therefore, basic research focuses on different symptoms and putative mechanisms, one at a time or in combination, to validate the hypotheses. Studies in several species, utilizing different preclinical approaches, have significantly contributed to the two antimigraine principles in therapeutics, namely: 5-HT(1B/1D) receptor agonists (known as triptans) and CGRP receptor antagonists (known as gepants). This review will analyze the preclinical experimental models currently known for the development of these therapeutic principles, which are mainly based on the vascular and/or neurogenic theories of migraine pathogenesis. These include models based on the involvement of cranial vasodilatation and/or the trigeminovascular system in migraine. Clearly, the preclinical strategies should involve both approaches, while incorporating the newer ideas/techniques in order to get better insights into migraine pathophysiology.

Relationship between substances in seminal plasma and Acrobeads Test results.

OBJECTIVE: To asses the effects of seminal plasma on sperm function. DESIGN: Retrospective case-control study. SETTING: University hospital. PATIENT(S): One hundred fourteen infertile men. INTERVENTION(S): Acrobeads Test scores (0-4) and measurement of interleukin (IL)-6, soluble IL-6 receptor, epidermal growth factor, insulin-like growth factor-I (IGF-I), transforming growth factor-beta I, superoxide dismutase, calcitonin, and macrophage migration inhibitory factor (MIF) levels in seminal plasma. MAIN OUTCOME MEASURE(S): Kruskal-Wallis test to compare the concentrations of substances as a nonparametric test for differences among Acrobeads Test scores and a multivariable logistic regression model to find independent risk factors associated with abnormal Acrobeads Test results. RESULT(S): The Acrobeads Test score was 0 for 7 samples, 1 for 20 samples, 2 for 18 samples, 3 for 28 samples, and 4 for 41 samples. Age, abstinence period, and semen parameters, except for sperm motility and percentage of sperm with abnormal morphology, had no effect on the Acrobeads Test results. Concentrations of IGF-I and MIF were significantly higher in patients with abnormal Acrobeads Test results. Multivariate analysis indicated that MIF and IGF-I were significantly associated with abnormal Acrobeads Test results (scores 0 to 1). CONCLUSION(S): Although further studies are needed, IGF-I and MIF in seminal plasma may have negative effects on sperm function.

The value of intraoperative pentagastrin testing in medullary thyroid cancer.

BACKGROUND: The decrease of calcitonin levels after curative operation in patients with medullary thyroid cancer is characterized by individual variation; therefore, intraoperative calcitonin measurements to evaluate the completeness of the resection seem to not be feasible. The aim of this study was to evaluate whether an intraoperative pentagastrin test after thyroidectomy and central neck dissection is useful to predict lymph node involvement of the lateral neck. METHODS: A group of 30 consecutive patients underwent primary surgery. After thyroidectomy and dissection of the central lymph node compartment, an intraoperative pentagastrin test was performed. Biochemical and histologic data were compared retrospectively. RESULTS: Of the group, 20 patients (67%) showed no, or only central neck lymph node, involvement and no increase in calcitonin after intraoperative stimulation. Lymph node involvement was documented histologically in the lateral neck of 10 patients (33%), and 8 patients showed an increase of calcitonin as an indication of lymph node involvement. In two patients, each with 1 single micrometastasis in the lateral neck, the intraoperative pentagastrin test was negative. CONCLUSIONS: Intraoperative calcitonin monitoring after pentagastrin stimulation seems promising in predicting lymph node involvement of the lateral neck to aid selection of patients for lateral lymph node dissection. The development of a highly sensitive, quick calcitonin assay is imperative.

Both mercury and cadmium directly influence calcium homeostasis resulting from the suppression of scale bone cells: the scale is a good model for the evaluation of heavy metals in bone metabolism.

To examine the effects of heavy metals such as cadmium and mercury on calcium homeostasis, plasma calcium and calcitonin were measured in goldfish. Cadmium induced hypocalcemia both at 4 and at 8 days. In methylmercury-treated goldfish, the plasma calcium level increased at 2 days and then decreased at 8 days. The plasma calcitonin level increased in correspondence with the increased plasma calcium by methylmercury treatment, although cadmium did not cause a significant change. To elucidate the mechanism in detail, fish scales, which have both osteoclasts and osteoblasts and are similar to mammalian membrane bone, were used in the present study. We measured tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) activity as respective indicators of activity in both types of cells. TRAP activity in the scales decreased by treatment of cadmium and methylmercury at 6 h incubation. Particularly, cadmium (even at 10(-13) M) significantly suppressed TRAP activity, suggesting that this system is utilized as an acute biosensor for cadmium. ALP activity decreased after exposures of 64 and 96 h, although the activity did not change after 6, 18, and 36 h. In addition, mRNA expression of the estrogen receptor and insulin-like growth factor 1, which participate in osteoblastic growth and differentiation, was less than the control values by treatment with both metals. This study demonstrates that mercury directly acts on the bone cells and influences calcium homeostasis and indicates that, in a short-term exposure, mercury has a different action from that of cadmium and induces hypercalcemia.

Modulation of the inflammatory response to cardiopulmonary bypass by dopexamine and epidural anesthesia.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory reaction. Microcirculation-dependent alteration of the gut mucosal barrier with subsequent translocation of endotoxins is a postulated mechanism for this inflammatory response. This study was designed to elucidate whether two different approaches to modulate splanchnic perfusion may influence systemic inflammation to CPB. METHODS: We examined 40 patients scheduled for elective coronary bypass surgery in a prospective, randomized study. One group (DPX) received dopexamine (1 micro g. kg-1. min-1) continuously after induction of anesthesia until 18 h after CPB. The control group (CON) received equal volumes of NaCl 0.9% in a time-matched fashion. In a third group (EPI) a continuous epidural infusion of bupivacaine 0.25% [(body height (cm) - 100). 10-1=ml.h-1] was administered for the whole study period. Procalcitonin (PCT), tumor necrosis factor (TNF-alpha), soluble TNF receptor, human soluble intercellular adhesion molecule-1, C-reactive protein (CRP) and leukocyte count were measured as parameters of inflammation. RESULTS: All parameters significantly increased following CPB. Increases of PCT, TNF-alpha and leukocyte count were significantly attenuated in the DPX and EPI groups at different time points. However, neither splanchnic blood flow nor oxygen delivery and consumption were different when compared with the CON-group. CONCLUSION: These results do suggest that mechanisms other than an improved splanchnic blood flow by DPX and EPI treatment have to be considered for the anti-inflammatory effects.

[Influence of dithranol therapy on clinical status and serum calcitonin concentrations in patients with common psoriasis]. / Wplyw leczenia cignolina na obraz kliniczny i wartosci stezenia kalcytoniny w surowicy u chorych na luszczyce.

The aim of this work was to study the effects of external dithranol therapy of psoriatic patients on the clinical status and serum calcitonin concentrations. This was done on 19 patients with common psoriasis using Cignoderm in the short contact therapy. Calcitonin concentration in serum samples was determined before and after a 14-day therapy. Results obtained before were compared with concentrations after dithranol treatment and with results in control group. Serum TSH was also measured in serum samples from both groups at the very beginning time. The determinations showed statistically significant lower serum TSH level in psoriatic patients before therapy vs. control and significant, negative correlation with calcitonin concentration in those patients. After a 14-day dithranol therapy a significant calcitonin concentration decrease as well as clinical effects were observed in the investigated group.

Induction of systemic serum procalcitonin and cardiocirculatory reactions after isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan.

OBJECTIVES: Isolated, hyperthermic limb perfusion (ILP) with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) and melphalan is a highly effective treatment for locoregional metastases of malignant melanoma and for advanced soft tissue sarcoma of the limb. The major systemic side effects are characterized by the induction of a systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT), a serum marker of bacterial sepsis, was investigated with respect to its role in SIRS after ILP. SETTING: University surgical oncology division with an integrated eight-bed intensive care unit. PATIENTS: Thirty-seven patients were treated by ILP with rhTNF-alpha and melphalan (n = 26) or with cytostatics alone (n = 11) for soft tissue sarcoma or malignant melanoma. INTERVENTIONS: The course of serum PCT, interleukin (IL)-6, and IL-8 was analyzed intra- and postoperatively. Hemodynamic variables including heart rate, mean arterial pressure, cardiac index, pulmonary arterial pressure, pulmonary capillary occlusion pressure, and pulmonary and systemic vascular resistance were recorded in parallel. MEASUREMENTS AND MAIN RESULTS: PCT was significantly elevated over baseline after ILP with a maximum between 8 hrs (peak level 16.0+/-18.8 (SD) ng/mL) and 36 hrs (13.8+/-15.7 ng/mL) (p < .001). The increase in serum PCT was significantly more pronounced after ILP with rhTNF-alpha/melphalan than after ILP with cytostatics alone (p < .001). IL-6 and IL-8 were also significantly increased after ILP (p = .001), reaching peak concentrations at 1 hr and 4 hrs postoperatively. Significant changes in heart rate, mean arterial pressure, cardiac index, and systemic vascular resistance were observed during and after ILP; however, PCT levels could not be correlated to these variables. Pulmonary arterial pressure, pulmonary capillary occlusion pressure, and pulmonary vascular resistance showed no significant changes. CONCLUSIONS: Serum procalcitonin is induced as part of the SIRS after ILP with rhTNF-alpha/melphalan. It may be induced directly by rhTNF-alpha or other cytokines, because serum peaks of IL-6 and IL-8 precede the peak of PCT. Because there is no correlation between serum levels of PCT and hemodynamic variables, this marker cannot be applied to assess the severity of SIRS reaction after ILP.

Surgical treatment of postoperative, incidentally diagnosed small sporadic C-cell carcinomas of the thyroid.

BACKGROUND AND AIMS: The surgical strategy in small sporadic C-cell carcinomas of the thyroid that are incidentally diagnosed after goiter resection for benign disease is controversial. It remains unclear whether a completion thyroidectomy should be performed in every case. PATIENTS AND METHODS: We present nine patients who were operated on between October 1992 and October 1997 in whom an unexpected, small sporadic C-cell carcinoma (seven with pT1, two with pT2) was found in the postoperative histology. RESULTS: All patients were calcitonin negative and there were no signs of the disease being inherited (no familial history, negative RET proto-oncogene). No patient underwent a completion thyroidectomy. All patients had a follow-up with pentagastrin-stimulated calcitonin and carcinoembryonic antigen (CEA) 3 months, 6 months and annually after the operation. No patient became calcitonin positive or showed any other signs of tumor recurrence after a follow-up period of 2-7 years. CONCLUSION: A completion thyroidectomy is not necessary in small sporadic C-cell carcinoma that is incidentally diagnosed after resection for benign disease if there is no sign of familial cancer and if calcitonin is negative. A close follow-up is necessary.

Minimally invasive surgery for recurrent neuroendocrine carcinoma of the supraglottic larynx.

Calcitonin-secreting neuroendocrine carcinomas of the supraglottic larynx are infrequent tumors, making it difficult to agree on treatment plans for recurrent tumors. Furthermore, this rare malignancy is often confused with the more common medullary thyroid carcinoma, resulting in inappropriate thyroidectomies. We present a case report of a calcitonin-secreting recurrent neuroendocrine carcinoma of the supraglottic larynx, in which surgery and pentagastrin stimulation were performed repeatedly at various stages of the disease. The recurrent laryngeal tumor was ultimately identified and, after construction of a protective tracheostomy, resected transorally en bloc with the underlying arytenoid cartilage. Postoperatively, the patient did well and stimulated calcitonin levels never exceeded double baseline values. Laryngoscopic removal of smaller laryngeal carcinomas is both technically feasible and safe, even when tumors are recurrent. In calcitonin-secreting malignancies, pentagastrin stimulation may facilitate the distinction between laryngeal and medullary thyroid carcinoma and thus help avoid unnecessary thyroidectomies.

Influence of laminin substratum on cell proliferation and CALC I gene expression in medullary thyroid carcinoma C cell lines.

Medullary thyroid carcinoma (MTC) originates from C cells, which secrete calcitonin (CT) and CT gene-related peptide (CGRP), the two splice peptide products of the CALC I gene. Normal and hyperplastic C cells are intrafollicular, in contact with the basement membrane (BM) that is maintained around the differentiated tumors. To investigate the relationships between MTC evolution and BM constituents, we examined the modifications induced by laminin-1 and -2 (merosin), two isoforms colocalized in the follicular BM, on three MTC cell lines: murine rMTC 6-23 and CA-77 cells, and human TT cells. Laminin exerted a mitogenic activity on rMTC 6-23 and on TT cells, causing a concurrent decrease in both CT and CGRP mRNA levels and production of the peptides. Conversely, laminin reduced the proliferation rate and enhanced CGRP synthesis and secretion in CA-77 cells. This antiproliferative response, which coincides with an increase in differentiation markers, is comparable to that reported in normal cells and also in the neoplastic Caco-2 cell line. This suggests that laminin could exert opposite effects depending on the stage of tumor evolution.

Evidence that peroral calcium does not activate the gastrin-ECL-cell axis in the rat.

The ECL cells are histamine- and pancreastatin-secreting endocrine cells in the oxyntic mucosa, thought to release a blood Ca2+-lowering peptide hormone upon stimulation by gastrin. Previously, we have shown that the ECL cells do not respond to perturbations in blood Ca2+. In the present study, we examine if Ca2+ in the gastric lumen will affect the activity of the gastrin-ECL-cell axis. Freely fed or food deprived (48 h) rats were given an oral load of CaCl2 (or NaCl), and the blood Ca2+ concentration was monitored. The serum gastrin concentration at sacrifice, 3 h after ingestion of CaCl2, was measured together with two parameters of ECL cell activity: the oxyntic mucosal histidine decarboxylase (HDC) activity and the serum pancreastatin concentration. The circulating concentrations of calcitonin and parathyroid hormone (PTH) were also measured. Oral CaCl2 raised the blood Ca2+ in a dose-dependent manner. The two highest doses (which caused damage to the oxyntic mucosa) raised the serum gastrin concentration and the HDC activity in both fed and fasted rats; the serum pancreastatin concentration remained unaffected. Oral CaCl2 raised the serum calcitonin concentration and lowered the serum PTH concentration. The effects of high doses of oral CaCl2 on the serum gastrin concentration and on the oxyntic mucosal HDC activity could be reproduced by a high dose of NaCl. Thus the effects are probably not due to Ca2+ per se. We conclude that the gastrin-ECL-cell axis in the rat does not respond to peroral Ca2+. Since the ECL cells do not respond to either circulating or peroral Ca2+ they are unlikely to secrete a calciotropic hormone.

1-alpha-Hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women.

50 Japanese women within 10 years after menopause (mean age 52.5 years) were studied to determine the effects of 0.75 microgram of 1-alpha-hydroxyvitamin D3 [1-alpha-(OH)D3] with calcium (150 mg/day) (treated group: N = 25) and calcium only (control group: N = 25) for 12 months on bone mass and metabolism. Their L2-4 BMD measurements were 1.5 SD below the mean value of Japanese young, normal women. L2-4 BMDs increased significantly in the treated group (+2.1%; p < 0.01), but decreased significantly in controls (-2.1%; p < 0.01). Although serum calcium and creatinine remained unchanged in both groups, phosphorus levels increased significantly in the treated group (p < 0.01). Urinary calcium/creatinine (Cr) increased in both groups. Urinary pyridinoline/Cr and deoxypyridinoline/Cr decreased significantly in the treated group (p < 0.05), but not in the control group. Serum osteocalcin levels remained unchanged in both groups. Intact parathyroid hormone levels decreased significantly (p < 0.05) and calcitonin levels significantly increased in the treated group (p < 0.05), but these changes were not observed in the control group. These data clearly demonstrate that 0.75 microgram of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by modulation of calcium-regulating hormones. Temporarily increased urinary calcium excretion was observed in control group, but did not appear to be effective in modulating bone turnover.

Regulation of calcitonin secretion by thyroid parafollicular cells in vitro.

The studies were performed on cultured TT cells originating from human thyroid medullary carcinoma (i.e., from parafollicular cells of the thyroid). The amount of released calcitonin was dependent upon calcium level in the medium. Moreover, calcitonin secretion might be regulated by medium supplementation with polypeptide hormones. Somatostatin inhibited while glucagon and pentagastrin stimulated calcitonin secretion to t he medium. Calcitonin secretion was also influenced by biogenic amines and their precursors. Dihydroxy-1-phenylalanine and serotonin augmented while 5-hydroxy-1-tryptophan and dopamine inhibited calcium secretion. This, calcitonin secretion may be controlled by different substances present in the healthy organism. This points to a complex control of calcium ion level in the blood.