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Sample records for calcitonin

  1. Assays for calcitonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  2. Calcitonin Salmon Injection

    Science.gov (United States)

    Calcitonin salmon injection is used to treat osteoporosis in postmenopausal women. Osteoporosis is a disease that causes bones to weaken and break more easily. Calcitonin salmon injection is also used to treat Paget's disease ...

  3. Analgesic effects of calcitonin.

    Science.gov (United States)

    Lyritis, G P; Trovas, G

    2002-05-01

    The analgesic activity of salmon calcitonin (subcutaneous or intranasal) has been demonstrated in several prospective clinical trials, in patients suffering different painful skeletal conditions, including recent nontraumatic osteoporotic vertebral fractures. The mechanism of the analgesic effect of calcitonin is not clear. It is possible that specific binding sites for salmon calcitonin exist in the brain. Another explanation is that changes in descending serotonergic modification on the sensory transmission mediated by C afferents contribute to the analgesic effects of calcitonin on pain in osteoporotic patients. From the clinical point of use, the analgesic effect of calcitonin is beneficial throughout the whole period of medical treatment of osteoporotic patients. Salmon calcitonin in a daily dose of 100 IU subcutaneously or 200 IU intranasally reduces dramatically the back pain (p salmon calcitonin effectively controls severe pain in osteoporotic patients with a recent vertebral fracture, allowing them earlier mobility in combination with a reduction of the urinary hydroxyproline excretion, and a limitation of the considerable bone loss that may occur during prolonged bed rest, make this therapeutic scheme attractive.

  4. Calcitonin Salmon Nasal Spray

    Science.gov (United States)

    ... is important that you get enough calcium and vitamin D while you are using calcitonin salmon. Your doctor ... symptoms such as crusts, dryness, redness, or swelling back pain joint pain upset stomach flushing (feeling of warmth) ...

  5. Renal metabolism of calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, R.E.; Hjelle, J.T.; Mahoney, C.; Deftos, L.J.; Lisker, W.; Kato, P.; Rabkin, R.

    1988-04-01

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with /sup 125/I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes.

  6. Calcitonin, a major gill hormone.

    OpenAIRE

    Milhaud, G; Bolis, L; Benson, A A

    1980-01-01

    Isolated salmon gills, under simulated in vivo conditions, transported calcium ion into the ambient seawater when perfused with Ringer's solution containing salmon calcitonin. Similar enhancement of phosphate efflux was observed. Calcitonin caused simultaneous decreases in perfusate flow rates. The effects act synergistically to diminish net plasma calcium concentrations.

  7. Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

    Directory of Open Access Journals (Sweden)

    Grabellus Florian

    2011-08-01

    Full Text Available Abstract Background Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice. Methods We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE particles in 10 C57BL/6J wild-type (WT mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1, WT with UHMWPE particles (Group 2, Calca -/- mice without UHMWPE particles (Group 3, Calca -/- mice with UHMWPE particles (Group 4, Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5, and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6. Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP + cells. Results Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin increased significantly after CT substitution. Conclusions As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

  8. Calcitonin

    Science.gov (United States)

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  9. Effects of calcitonin on the osteoporotic skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Agrawal, R.; Wallach, S.; Cohn, S.; Wu, T.; Tessier, M.; Verch, R.; Hussain, M.; Zanzi, I.

    1981-01-01

    Synthetic salmon calcitonin at a dose of 100 MRC units daily was administered to nine biopsy-proven osteoporotic men, aged 50 years and older, for one to two years. Two additional groups of men with comparable degrees of osteoporosis received either multivitamins alone or multivitamins plus a calcium supplement. The group treated with salmon calcitonin increased their total body calcium by 3% at the end of two years, whereas no change was seen in the other two groups. This result was not statistically significant because of dispersion of the data. There was also no significant changes in bone mineral content of the distal forearm. Four of the nine men treated with calcitonin had increases in total body calcium, which exceeded the reproducibility of the in vivo neutron activation method by 2 SD (SD +- 1.1%). The mean increase in total body calcium in these four patients was 8% compared to a mean decrease of 2 to 4% in the remainder. New vertebral compression and/or collapse was significantly less frequent in the group treated with calcitonin (1.0 +- 0.6 per patient) compared to the other two groups (2.4 +- 0.8 and 2.0 +- 0.6 per patient). These data support the thesis that calcitonin can increase skeletal mass in selected osteoporotic patients and justify further studies to detect responsive patients and to amplify the effect of calcitonin in such patients. 5 references.

  10. The calcitonin gene is expressed in salmon gills.

    OpenAIRE

    Martial, K; Maubras, L; Taboulet, J; Jullienne, A; M. Berry; Milhaud, G; Benson, A A; Moukhtar, M S; Cressent, M

    1994-01-01

    Calcitonin is an important physiological regulator of salmon gills. Although the calcitonin receptor was found in salmon gills, the critical question concerning the source of the hormone remained unanswered. In this communication, evidence is presented for expression of calcitonin mRNA and its encoded peptide in gills of the pink salmon, Oncorhynchus gorbuscha. The expression of calcitonin gene transcripts was demonstrated by reverse transcription-polymerase chain reaction, Southern hybridiza...

  11. Determination of calcitonin; Bestimmung von Kalzitonin

    Energy Technology Data Exchange (ETDEWEB)

    Goerges, R. [Klinik fuer Nuklearmedizin, Klinikum Essen, Univ. Duisburg/Essen (Germany); Gemeinschaftspraxis fuer Nuklearmedizin, Duisburg (Germany)

    2005-03-01

    Calcitonin in serum is a comparatively highly sensitive, specific and reliable tumor marker of central relevance for the diagnosis and follow-up of medullary thyroidal C-cell carcinoma (MTC) and neoplastic C-cell hyperplasia (CCH). It is seen considerably less often in other tumor entities. For determination we recommend immunometric two-site assays of approximately 1-2 pg/ml sensitivity. Higher MTC specificity is achieved by assays focussing on a largely selective determination of monomeric calcitonin. If this is realized, basal calcitonin levels are already greatly relevant for MTC or CCH diagnosis. The diagnostic sensitivity and specificity of calcitonin determination may be further enhanced by means of pentagastrin test, but even then false positive results are clinically relevant especially in benign CCH and renal insufficiency. In family screening in case of MTC patients, moleculargenetic techniques have become the procedure of choice and have now largely replaced the pentagastrin test. Calcitonin screening in adenomatous goitre (struma nodosa) is making headway. Although this accounts for only 10% of thyroidal malignomas (which are in fact rare), and the recommended levels of intervention will result in many unnecessary surgical operations, early tumor staging definitely increases the chances for curative intervention. (orig.)

  12. Whisky: a new provacative test for calcitonin secretion.

    Science.gov (United States)

    Dymling, J F; Ljungberg, O; Hillyard, C J; Greenberg, P B; Evans, I M; MacIntyre, I

    1976-07-01

    Oral whisky is a potent stimulus of calcitonin secretion. Peak increments of immunoreactive calcitonin are observed within 15 min after the ingestion of 50 ml of whisky; the magnitude of the response is similar to that observed during a four-hour calcium infusion. This procedure has several advantages over standard methods of stimulating calcitonin release in patients at risk of developing medullary carcinoma of the thyroid, and this is shown by a study in a large family with familial chromaffinomatosis.

  13. Morning or evening administration of nasal calcitonin?

    DEFF Research Database (Denmark)

    Schlemmer, A; Ravn, Pernille; Hassager, C;

    1997-01-01

    The purpose of this study was to examine the effect of intranasal salmon calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or evening (21:00), on the known circadian variation in biochemical markers of bone turnover. An open, placebo-controlled, randomized, crossover......). Serum osteocalcin (sOC) was measured by radioimmunoassay (RIA). The first 24 h study was performed without intervention. Prior to this control study the participants were randomized to either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were given 4-5 days prior to and during...... in late afternoon. Both morning and evening administration of sCT significantly decreased the urinary excretion of CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound effect. sOC did not exhibit a significant circadian variation and was not affected by the calcitonin. The 24 h...

  14. Elucidation of the nucleotide sequence of chicken calcitonin mRNA: direct evidence for the expression of a lower vertebrate calcitonin-like gene in man and rat.

    OpenAIRE

    Lasmoles, F.; Jullienne, A; Day, F; Minvielle, S.; Milhaud, G; Moukhtar, M S

    1985-01-01

    Calcitonin shows considerable divergence in amino acid sequence between lower vertebrates and higher vertebrates. Immunoreactive salmon-like calcitonin molecules are present in the thyroid of man and rat. Elucidation of the almost complete sequence of chicken calcitonin mRNA revealed that the calcitonin precursor in chickens had the same organisation as in higher vertebrates (man and rat) but showed considerable differences in amino acid sequence. cDNA probes specific for chicken calcitonin m...

  15. Role of calcitonin in management of musculoskeletal pain

    Directory of Open Access Journals (Sweden)

    Lars Arendt-Nielsen

    2009-12-01

    Full Text Available Calcitonin was discovered more than 40 years ago and the scientific community continues to debate the primary and secondary pharmacological actions of calcitonin. Presently calcitonin is accepted by agencies only for treatment of osteoporosis, but many studies have indicated an effect on pain in many different experimental settings both pre-clinically and clinically. The effects of calcitonin on clinical pain conditions have received increasing attention in the past decades, although a consensus on mode of action and potential indications still has to be reached. Several key advances in the pain field may enable a deeper understanding of the putative analgesic effects of calcitonin. Most studies have focused on the effect of calcitonin on musculoskeletal pain problems. Ample lines of independent evidence suggest that calcitonin exerts putative analgesic effects. Well-designed clinical trials, particularly in the field of musculoskeletal pain, are needed to validate fragmented evidence of analgesic actions. This in combination with advanced mechanism-based pain assessment tools can provide new insight into the role of calcitonin, alone or in combination with other compounds, in management of pain.

  16. Calcitonin-like diuretic hormones in insects.

    Science.gov (United States)

    Zandawala, Meet

    2012-10-01

    Insect neuropeptides control various biological processes including growth, development, homeostasis and reproduction. The calcitonin-like diuretic hormone (CT/DH) is one such neuropeptide that has been shown to affect salt and water transport by Malpighian tubules of several insects. With an increase in the number of sequenced insect genomes, CT/DHs have been predicted in several insect species, making it easier to characterize the gene encoding this hormone and determine its function in the species in question. This mini review summarizes the current knowledge on insect CT/DHs, focusing on mRNA and peptide structures, distribution patterns, physiological roles, and receptors in insects.

  17. Pulp response after calcitonin treatment of direct exposures in the dog.

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    Cullum, D R; Kline, L W

    1985-08-01

    The hypocalcemic hormone, calcitonin, was used in directly pulp-capped teeth to determine whether or not calcitonin promoted healing. Two dogs were used. Twelve teeth received the calcitonin; nine control teeth were prepared, and five were treated with calcium hydroxide. Calcitonin did not increase either the rate of healing or the amount of secondary dentin formed. Calcitonin reduced the degree of inflammation in the treated tooth pulps.

  18. Salmon calcitonin: a review of current and future therapeutic indications.

    Science.gov (United States)

    Chesnut, C H; Azria, M; Silverman, S; Engelhardt, M; Olson, M; Mindeholm, L

    2008-04-01

    Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.

  19. Salmon calcitonin in the prevention and treatment of osteoporosis.

    Science.gov (United States)

    Avioli, L V

    1997-04-01

    The principal calcitonins used therapeutically are porcine, human (synthetic), salmon (synthetic), and eel. Of these substances, salmon calcitonin is the most potent (Reginster 1991). Injectable forms of salmon calcitonin were first indicated for use in the treatment of Paget's disease in the United States and later received an indication for use in the treatment of postmenopausal osteoporosis. The injectable [intramuscular (IM) or subcutaneous (SC)] formulation of salmon calcitonin, however, has been associated with a high rate of noncompliance in elderly patients. The recently approved nasal-spray formulation has ameliorated the difficulties inherent in parenteral administration and is considered a suitable option as an alternative therapy in patients who are not appropriate candidates for estrogen replacement therapy. (Trends Endocrinol Metab 1997;8:89-92). (c) 1997, Elsevier Science Inc.

  20. Inhibitory effect of calcitonin on pure human pancreatic secretion.

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    Tanaka,Juntaro

    1989-06-01

    Full Text Available The inhibitory effect of calcitonin on human pancreatic secretion was evaluated to examine whether the different results reported earlier between humans, cats and dogs can be ascribed to the different sensitivity of these species to calcitonin, as suggested by some investigators. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct from 11 patients with relapsing pancreatitis during intravenous infusion of secretin (1 U/kg/h plus caerulein (0.04 microgram/kg/h. After steady secretion was attained 20 min after the beginning of collection, five 2-min fractions were obtained before, and ten 2-min fractions were obtained after intravenous infusion of calcitonin (1 IU/kg/h. The pre- and post-calcitonin fractions from each patient were compared by Student's t-test. Calcitonin inhibited the secretory volume (26.8 to 65.6% and bicarbonate secretion (21.4 to 62.0% in 8 patients, and amylase (48.4 to 89.5% and lipase secretion (47.4 to 90.5% in all patients. The present studies reconfirmed that prominent inhibition of enzyme secretion occurs in humans. A new finding was that significant inhibition of the secretory volume and bicarbonate secretion occurs in humans. The inhibitory effects of calcitonin in humans did not appear to differ from those in cats and dogs, when evaluated similarly with the use of pure pancreatic juice.

  1. Binding of a candidate splice regulator to a calcitonin-specific splice enhancer regulates calcitonin/CGRP pre-mRNA splicing.

    Science.gov (United States)

    Coleman, Timothy P; Tran, Quincy; Roesser, James R

    2003-01-27

    The calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA is alternatively processed in a tissue-specific manner leading to the production of calcitonin mRNA in thyroid C cells and CGRP mRNA in neurons. A candidate calcitonin/CGRP splice regulator (CSR) isolated from rat brain was shown to inhibit calcitonin-specific splicing in vitro. CSR specifically binds to two regions in the calcitonin-specific exon 4 RNA previously demonstrated to function as a bipartate exonic splice enhancer (ESE). The two regions, A and B element, are necessary for inclusion of exon 4 into calcitonin mRNA. A novel RNA footprinting method based on the UV cross-linking assay was used to define the site of interaction between CSR and B element RNA. Base changes at the CSR binding site prevented CSR binding to B element RNA and CSR was unable to inhibit in vitro splicing of pre-mRNAs containing the mutated CSR binding site. When expressed in cells that normally produce predominantly CGRP mRNA, a calcitonin/CGRP gene containing the mutated CSR binding site expressed predominantly calcitonin mRNA. These observations demonstrate that CSR binding to the calcitonin-specific ESE regulates calcitonin/CGRP pre-mRNA splicing.

  2. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias.

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    Kim Vietz Andreassen

    Full Text Available Salmon calcitonin (sCT and human calcitonin (hCT are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(aR with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a receptor. CT(aR downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours and prolonged (up to 72 hours stimulation. CT(aR kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(aR downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo.

  3. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias.

    Science.gov (United States)

    Andreassen, Kim Vietz; Hjuler, Sara Toftegaard; Furness, Sebastian G; Sexton, Patrick M; Christopoulos, Arthur; Nosjean, Olivier; Karsdal, Morten Asser; Henriksen, Kim

    2014-01-01

    Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a) receptor. CT(a)R downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours) and prolonged (up to 72 hours) stimulation. CT(a)R kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(a)R downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo.

  4. Salmon calcitonin: conformational changes and stabilizer effects

    Directory of Open Access Journals (Sweden)

    Shan-Yang Lin

    2015-11-01

    Full Text Available The therapeutic activity of peptides or protein drugs is highly dependent on their conformational structure. The protein structure is flexible and responds to external conditions, which may compromise the protein's native conformation and influence its physical and chemical stability. The physical and chemical stability of peptides or protein drugs are important characteristics of biopharmaceutical products. Calcitonin (CT is a polypeptide hormone that participates in diverse physiological functions in humans; therefore, it is a potentially useful protein for investigations of different aspects of pharmacology and drug delivery systems. Of the different types of CT available for clinical use, salmon CT (sCT is one of the most potent. In this review article, the commercially available sCT was selected as a suitable peptide candidate for the discussion of its stability and conformational changes in the aqueous and solid states using Fourier transform infrared (FTIR spectroscopic analysis under different external conditions, including pH, temperature, drying method, and added excipients. Particularly, excipients that have been optimized as stabilizers of sCT in aqueous solution and as lyophilized and spray-dried drug formulations are also discussed.

  5. Calcitonin gene related peptide and its functions

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    Karimian M

    1998-07-01

    Full Text Available Calcitonin Gene Related Peptide (CGRP was first reported in 1982. This peptide contains 37 amino acids which could be found in Alpha and Beta forms. CGRP shows diversity both in its receptors and biological effects and up to now four different types of receptors have been reported. It can act like a neurotransmitter, local hormone and neuromodulator. They have a variety of effects on different organs such as a potent effect on vasodilation and smooth muscle relaxation. Ability of CGRP for induction of protein extravasation from blood vessels was uncertain. In this study intra-articular infusion of 10^-6 M CGRP to the rat knee joint induced significant protein extravasation into the rat knee joint space. The amount of protein was detected by modified Iawata method which could detect amount of protein between 5-500 mg/L. Higher and lower concentrations failed to induce protein extravasation. Failure in higher concentration was likely due to significant fall in blood pressure. In the presence of an arterial hypotension induced by an ? adenoreceptor antagonist, 10^-6 M of CGRP failed to produce protein extravasation. This effect of CGRP was a specific active effect and not a passive effect due to its potent vasodilation effect, as similar vasodilatory response induced by a ?-adrenoreceptor agonist failed to induce protein extravasation. There is more than 50% of sensory neurons which contain CGRP and they are spread in all over the body and joints, therefore CGRP induced protein extravasation can potentiate inflammation in different organs.

  6. Improving oral absorption of Salmon calcitonin by trimyristin lipid nanoparticles.

    Science.gov (United States)

    Martins, S; Silva, A C; Ferreira, D C; Souto, E B

    2009-02-01

    Solid lipid nanoparticles (SLN) composed of trimyristin (solid lipid) and poloxamer 407 (surfactant) were prepared by a w/o/w emulsion technique for the incorporation of Salmon calcitonin, and further explored as protein carriers for oral delivery. Trimyristin SLN showed a mean size diameter of 200 nm with an association efficiency for calcitonin of approx. 86%. The morphology of SLN was investigated by cryo-SEM and by AFM, revealing spheroid shape SLN with a smooth surface. The in vitro release of calcitonin occurred for a period of 8 h, under both gastric and intestinal simulated pH conditions, predicting suitable properties for oral administration. The pharmacological activity of the protein was evaluated following oral dosage of calcitonin-loaded SLN in rats. SLN lowered the basal blood calcium levels by up to 20% with 500 IU/kg dose sustaining hypocalcaemia over 8 h. The results indicate that incorporation of Salmon calcitonin into trimyristin SLN is a key factor for the improvement of the efficiency of such carriers for oral delivery of proteins.

  7. Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidence by autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Bouizar, Z.; Rostene, W.H.; Milhaud, G.

    1987-08-01

    In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with /sup 125/I-labeled sCT. Autoradiograms demonstrated a heterogeneous distribution of /sup 125/I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert it physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites.

  8. Scientific considerations for generic synthetic salmon calcitonin nasal spray products.

    Science.gov (United States)

    Lee, Sau L; Yu, Lawrence X; Cai, Bing; Johnsons, Gibbes R; Rosenberg, Amy S; Cherney, Barry W; Guo, Wei; Raw, Andre S

    2011-03-01

    Under the Abbreviated New Drug Application pathway, a proposed generic salmon calcitonin nasal spray is required to demonstrate pharmaceutical equivalence and bioequivalence to the brand-name counterpart or the reference listed drug. This review discusses two important aspects of pharmaceutical equivalence for this synthetic peptide nasal spray product. The first aspect is drug substance sameness, in which a proposed generic salmon calcitonin product is required to demonstrate that it contains the same active ingredient as that in the brand-name counterpart. The second aspect is comparability in product- and process-related factors that may influence immunogenicity (i.e., peptide-related impurities, aggregates, formulation, and leachates from the container/closure system). The comparability of these factors helps to ensure the product safety, particularly with respect to immunogenicity. This review also highlights the key features of in vitro and/or in vivo studies for establishing bioequivalence for a solution nasal spray containing a systemically acting salmon calcitonin.

  9. Salmon calcitonin in the therapy of corticoid-induced osteoporosis.

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    Ringe, J D; Welzel, D

    1987-01-01

    There is uncertainty about the best treatment for steroid-induced osteoporosis. Thirty-six patients with steroid-dependent, chronic obstructive lung disease and associated steroid osteoporosis have been studied, of whom 18 were treated with salmon calcitonin and the other 18 served as controls. Treatment lasted for 6 months and consisted of 100 I.U.s.c. every other day. In the controls there were significant decrements of 1.4% and 3.5%, respectively, in cortical and cortical and trabecular bone mineral content, whereas in subjects on calcitonin there were increments of 2.6% and 2.7%, respectively. Additional evidence of positive effect of calcitonin was derived from the reduced incidence of new fractures occurring during the observation period. A significant reduction in back pain was a further consequence of the hormone therapy.

  10. Calcitonin, as SMS 201-995, ameliorates the VIPoma syndrome.

    Science.gov (United States)

    Antonelli, A; Gambuzza, C; Bertoni, F; Baschieri, L

    1993-01-01

    A 72-year-old woman was referred to our hospital for diarrhea, abdominal and back pain, weight loss, low serum potassium level. Pathological findings and high circulating Vasoactive Intestinal Peptide (VIP) levels allowed us to diagnose "VIPoma syndrome". The patient underwent a treatment with SMS 201-995 with improvement of symptomatology and reduction of circulating VIP levels. After a wash-out period the patient was treated with salmon calcitonin with a net improvement of diarrhea, normalization of potassium serum level and reduction of VIP level. The symptomatology recurred after calcitonin withdrawal. These data confirm the effectiveness of SMS 201-995 in the VIPoma syndrome and suggest that calcitonin may ameliorate symptomatology and reduce circulating VIP level in patients with VIPoma tumor.

  11. [Calcitonin as an alternative treatment for root resorption].

    Science.gov (United States)

    Pierce, A; Berg, J O; Lindskog, S

    1989-01-01

    Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption.

  12. Calcitonin Gene-Related Peptide (CGRP in Cerebrovascular Disease

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    Lars Edvinsson

    2002-01-01

    Full Text Available Cerebral blood vessels are innervated by sensory nerves that store several neurotransmitters among which calcitonin gene-related peptide (CGRP is the most abundant. In primary headaches, there is a clear association between the head pain and the release of CGRP. In cluster headache there is an additional release of vasoactive intestinal peptide (VIP.

  13. Calcitonin gene-related peptide and adrenomedullin release in humans

    DEFF Research Database (Denmark)

    Hasbak, Philip; Lundby, Carsten; Olsen, Niels Vidiendal;

    2002-01-01

    ). Plasma values of CGRP, AM, calcitonin, noradrenaline, adrenaline, lactate and heart rate were measured at rest and during maximal exercise (W(max)). On each study day, the dopamine D(2)-receptor antagonist, domperidone (30 mg; n=6), or no medication (n=6) was given 1 h before exercise. W(max) at SL, HA1...

  14. 21 CFR 862.1140 - Calcitonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Calcitonin test system. 862.1140 Section 862.1140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  15. Specific binding of /sup 125/I-salmon calcitonin to rat brain. Regional variation and calcitonin specificity

    Energy Technology Data Exchange (ETDEWEB)

    Nakamuta, H.; Furukawa, S.; Koida, M. (Nagasaki Univ. (Japan). Faculty of Pharmaceutical Sciences); Yajima, H.; Orlowski, R.C.

    1981-02-01

    Rat brain particulate fraction was found to contain binding sites for /sup 125/I-Salmon Calcitonin-I (/sup 125/I-SCT). Maximum binding occurred in the physiological pH range of 7.25 - 7.5. The binding reaction proceeded in a temperature-dependent manner. Binding sites were broadly distributed among the various rat brain regions and considerable regional differences existed in the affinity and density as detected by Scatchard analysis. The highest affinity was recorded in the case of the hypothalamus and the lowest in the case of the cerebellum. The KD (nM) and Bmax (pmole/mg protein) estimated for the binding to four regions were as follows: hypothalamus: 1.4 and 0.19, midbrain, hippocampus plus striatum: 1.5 and 0.08, pon plus medulla oblongata: 3.0 and 0.15 and cerebellum: 8.3 and 0.20. Using a particulate fraction of rat brain void of cerebellum and cortices, a binding assay for calcitonins was developed. Binding of /sup 125/I-SCT was inhibited by unlabeled salmon, (Asu sup(1,7))-eel and porcine calcitonins in a dose-dependent manner and the IC50s were 2.0, 8.0 and 30 nM, respectively. The IC50s were comparable to those estimated using a kidney particulate fraction. Human calcitonin, ..beta..-endorphin and substance P were weak inhibitors of the binding. Other peptides, drugs and putative neurotransmitters tested (totally 23 substances) failed to inhibit the binding at concentrations of 1.0 ..mu..M. The physiological significance of brain binding sites for calcitonin, with the possibility that the brain may possess endogenous ligands for these sites are discussed.

  16. Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes

    Directory of Open Access Journals (Sweden)

    Pedersen Christian

    2010-04-01

    Full Text Available Abstract Background Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA cartilage. Methods Human OA cartilage explants were cultured with salmon calcitonin [100 pM-100 nM]. Direct effects of calcitonin on articular cartilage were evaluated by 1 measurement of proteoglycan synthesis by incorporation of radioactive labeled 35SO4 [5 μCi] 2 quantification of collagen-type-II formation by pro-peptides of collagen type II (PIINP ELISA, 3 QPCR expression of the calcitonin receptor in OA chondrocytes using four individual primer pairs, 4 activation of the cAMP signaling pathway by EIA and, 5 investigations of metabolic activity by AlamarBlue. Results QPCR analysis and subsequent sequencing confirmed expression of the calcitonin receptor in human chondrocytes. All doses of salmon calcitonin significantly elevated cAMP levels (P 35SO4 incorporation, with a 96% maximal induction at 10 nM (P Conclusion Calcitonin treatment increased proteoglycan and collagen synthesis in human OA cartilage. In addition to its well-established effect on subchondral bone, calcitonin may prove beneficial to the management of joint diseases through direct effects on chondrocytes.

  17. Identification of the calcitonin receptor in osteoarthritic chondrocytes

    Directory of Open Access Journals (Sweden)

    Christensen Tjorbjoern

    2011-10-01

    Full Text Available Abstract Background Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA. However, the presence of the calcitonin receptor (CTR in articular cartilage chondrocytes is yet to be identified. In this study, we sought to further investigate the expression of the CTR in naïve human OA articular chondrocytes to gain further confirmation of the existents of the CTR in articular cartilage. Methods Total RNA was purified from primary chondrocytes from articular cartilage biopsies from four OA patients undergoing total knee replacement. High quality cDNA was produced using a dedicated reverse transcription polymerase chain reaction (RT-PCR protocol. From this a nested PCR assay amplifying the full coding region of the CTR mRNA was completed. Western blotting and immunohistochemistry were used to characterize CTR protein on protein level in chondrocytes. Results The full coding transcript of the CTR isoform 2 was identified in all four individuals. DNA sequencing revealed a number of allelic variants of the gene including two potentially novel polymorphisms: a frame shift mutation, +473del, producing a shorter form of the receptor protein, and a single nucleotide polymorphism in the 3' non coding region of the transcript, +1443 C>T. A 53 kDa protein band, consistent with non-glycosylated CTR isoform 2, was detected in chondrocytes with a similar size to that expressed in osteoclasts. Moreover the CTR was identified in the plasma membrane and the chondrocyte lacuna of both primary chondrocytes and OA cartilage section. Conclusions Human OA articular cartilage chondrocytes do indeed express the CTR, which makes the articular a pharmacological target of salmon calcitonin. In addition, the results support previous findings suggesting that calcitonin has a direct anabolic effect on articular cartilage.

  18. Calcitonin gene-related peptide and migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Ashina, Messoud

    2014-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathophysiology. Most studies have focused on CGRP in relation to migraine without aura (MO). About one-third of migraine patients have attacks with aura (MA), and this is a systematic review of the current literature...... of CGRP in MA is less studied than in MO. Further studies of the importance of CGRP for auras and migraine are needed....

  19. Effect of Acupuncture on Calcitonin in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    ZHAORong; LIUChuyu; LVGuangrong; CAOJianming; LIQingyun

    2003-01-01

    Objective To Explore the mechanism of the acupuncture on posanenopausal osteoporo-sis.Method One hundred Wistar female rats(6 month- old)were randomly divided into two groups: O-variectomized group and sham - operated group. After 3 months of operation, three rats were chosen tomeasure the bone histomorphometric indexes. Then the ovariectomized rats were distributed randomly to acupuncture group and yigaining group and normal saline group and control 2 group, the rats were respec-tively treated by acupuncture and yigaining and normal saline. After the treatment for three course, all rats were collected blood from the ateria femoralis, the levels of calcitonin were measured by IRMA. the bone histomorphometric indexes and C - cell in thyroid follicle were detected. Results The levels of calcitonin of acupuncture group were increasing significantly comparing with the yigaining group and the normal saline group and the control 2 group ( p < 0.05), but there were no evident difference in the levels of cal-citonin between the acupuncture group and the sham - operated group. The mean trabecular bone width and the tmbecuhar bone volume % of acupuncture group were increasing more than that of the normal saline group and the control 2 group(p < 0.05) ;the mean marrow cavity width and the marrow cavity vol-ume % were derreasing more than that of the nomal saline group and the control 2 group( P < 0.05) ; the number of C - cell in thyroid follicle of the acupuncture group were increasing more than that of the other groups except the sham - operated group. Conclusion Acupuncture can effectively treat the post-menopausal osteoporosis by strengthening the ability of the C - cell in thyroid follicle which can improve the levels of calcitonin in serum.

  20. Conformational flexibility in calcitonin: The dynamic properties of human and salmon calcitonin in solution

    Energy Technology Data Exchange (ETDEWEB)

    Amodeo, Pietro; Motta, Andrea; Strazzullo, Giuseppe [Istituto per la Chimica di Molecole di Interesse Biologico, Istituto Nazionale di Chimica dei sistemi Biologici del CNR (Italy); Castiglione Morelli, Maria A. [Universita della Basilicata, Dipartimento di Chimica (Italy)

    1999-02-15

    We have studied the dynamic properties of human (h) and salmon (s) calcitonin (CT) in solution. For both hormones, distance geometry in torsion-angle space has been used to generate three-dimensional structures consistent with NMR data obtained in sodium dodecyl sulfate micelles. For sCT and hCT we used, respectively, 356 and 275 interproton distances together with hydrogen-bonds as restraints. To better characterize their flexibility and dynamic properties two fully unrestrained 1100-ps molecular dynamics (MD) simulations in methanol were performed on the lowest-energy structures of both hormones. Statistical analyses of average geometric parameters and of their fluctuations performed in the last 1000 ps of the MD run show typical helical values for residues 9-19 of sCT during the whole trajectory. For hCT a shorter helix was observed involving residues 13-21, with a constant helical region in the range 13-19. Angular order parameters S({phi}) and S({psi}) indicate that hCT exhibits a higher flexibility, distributed along the whole chain, including the helix, while the only flexible amino acid residues in sCT connect three well-defined domains. Finally, our study shows that simulated annealing in torsion-angle space can efficiently be extended to NMR-based three-dimensional structure calculations of helical polypeptides. Furthermore, provided that a sufficient number of NMR restraints describes the system, the method allows the detection of equilibria in solution. This identification occurs through the generation of 'spurious' high-energy structures, which, for right-handed {alpha}-helices, are likely to be represented by left-handed {alpha}-helices.

  1. Activities of calcitonin gene-related peptide (CGRP) and related peptides at the CGRP receptor

    Energy Technology Data Exchange (ETDEWEB)

    Maton, P.N.; Pradhan, T.; Zhou, Z.C.; Gardner, J.D.; Jensen, R.T. (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA))

    1990-05-01

    In guinea pig pancreatic acini rat calcitonin gene-related peptide (CGRP) increased amylase release 2-fold, salmon calcitonin had an efficacy of only 44% of that of CGRP and (Tyr0)CGRP(28-37) and human calcitonin had no actions. (Tyr0)CGRP(28-37), but not human calcitonin, antagonized the actions of CGRP in pancreatic acini with an IC50 of 3 microM. (Tyr0)CGRP(28-37) produced a parallel rightward shift in the dose-response curve for CGRP-stimulated amylase secretion. The inhibition was specific for CGRP and was reversible. Studies with 125I-CGRP demonstrated that CGRP, salmon calcitonin and (Tyr0)CGRP, but not human calcitonin, interacted with CGRP receptors on pancreatic acini. These results indicate that various CGRP-related peptides demonstrate different relationships between their abilities to occupy the CGRP receptor and to affect biologic activity, with CGRP itself being a full agonist, salmon calcitonin a partial agonist, (Tyr0)CGRP(28-37) a competitive antagonist, and human calcitonin having no actions.

  2. Novel Secondary Structure of Calcitonin in Solid State as Revealed by Circular Dichroism Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    DU,Hai-Ning(杜海宁); DING,Jin-Guo(丁金国); CUI,Da-Fu(崔大敷); HU,Hong-Yu(胡红雨)

    2002-01-01

    The solid-state circular dichroic study reveals that salmon calcitonin presents a typical α-helical structure while human calcitonin appears to form a β-sheet in solid state, although both of them adopt random coil structures in aqueous solution.

  3. Stability aspects of salmon calcitonin entrapped in poly(ether-ester) sustained release systems

    NARCIS (Netherlands)

    Dijkhuizen-Radersma, van R.; Nicolas, H.M.; Weert, van de M.; Blom, M.; Groot, de K.; Bezemer, J.M.

    2002-01-01

    Poly(ether-ester)s composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were studied as matrix for the controlled release of calcitonin. Salmon calcitonin loaded PEGT/PBT films were prepared from water-in-oil emulsions. T

  4. Salmon calcitonin reduces oxaliplatin-induced cold and mechanical allodynia in rats.

    Science.gov (United States)

    Aoki, Manahito; Mori, Asami; Nakahara, Tsutomu; Sakamoto, Kenji; Ishii, Kunio

    2013-01-01

    Oxaliplatin is commonly used anti-cancer drugs, but it frequently causes peripheral neuropathic pain. Recently, we reported that elcatonin, a synthetic analog of eel calcitonin, attenuated the oxaliplatin- and paclitaxel-induced cold and mechanical allodynia in rats. In the present study, we determined whether salmon calcitonin also had anti-allodynic effects on oxaliplatin-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, intraperitoneally (i.p.)). Oxaliplatin resulted in cold and mechanical allodynia. We assessed the anti-allodynic effects of subcutaneously administered salmon calcitonin (20 U/kg/d) by cold stimulation (8°C) directly to the hind paw of the rats and by using the von Frey test. Salmon calcitonin almost completely reversed the effects of both cold and mechanical allodynia. These results suggest that salmon calcitonin is also useful for treatment of oxaliplatin-induced neuropathy clinically.

  5. Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors

    Directory of Open Access Journals (Sweden)

    Ito Akitoshi

    2012-06-01

    Full Text Available Abstract Background The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats. Results Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG, which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. Conclusions These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.

  6. Effect of Acupuncture on Calcitonin in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Rong; LIU Chuyu; LV Guangrong; CAO Jianming; LI Qingyun

    2003-01-01

    Objective To Explore the mechanism of the acupuncture on postmenopausal osteoporosis. Method One hundred Wistar female rats(6 month-old)were randomly divided into two groups:Ovariectomized group and sham - operated group. After 3 months of operation, three rats were chosen tomeasure the bone histomorphometric indexes. Then the ovariectomized rats were distributed randomly toacupuncture group and yigaining group and normal saline group and control 2 group,the rots were respec-tively treated by acupuncture and yigaining and normal saline. After the treatment for three course, all ratswere collected blood from the ateria femoralis, the levels of calcitonin were measured by IRMA. The bonehistomorphometric indexes and C - cell in thyroid follicle were detected. Results The levels of calcitoninof acupuncture group were increasing significantly comparing with the yigaining group and the normalsaline group and the control 2 group (p < 0.05),but there were no evident difference in the levels of cal-citonin between the acupuncture group and the sham - operated group. The mean trabecular bone widthand the trabecular bone volume % of acupuncture group were increasing more than that of the normalsaline group and the control 2 group(p < 0.05) ;the mean marrow cavity width and the marrow cavity volume % were derreasing more than that of the nomal saline group and the control 2 group(P < 0.05) ;thenumber of C - cell in thyroid follicle of the acupuncture group were increasing more than that of the othergroups except the sham - operated group. Conclusion Acupuncture can effectively treat the post-menopausal osteoporosis by strengthening the ability of the C - cell in thyroid follicle which can improvethe levels of calcitonin in serum.

  7. Salmon calcitonin in prevention of osteoporosis in maintenance dialysis patients

    Institute of Scientific and Technical Information of China (English)

    WANG Shi-xiang; LI Han

    2008-01-01

    Background Renal osteodystrophy is one of the commonest complications of chronic renal failure. It may have a severe impact on the quality of life of patients on maintenance dialysis therapy. Besides post-menopausal women and elderly people, the dialysis patients are another high risk group. But at present, there is no research on how to prevent osteoporosis in maintenance dialysis patients. This study was conducted to observe the bone density of maintenance dialysis patients and to evaluate the clinical outcomes and safety of different administration dosage of salmon calcitonin to prevent osteoporosis in maintenance dialysis patients.Methods One hundred and forty-eight patients on maintenance dialysis were involved in the 12-month, randomized, controlled trial. Fifty patients (experiment Ⅰ group) received subcutaneous injection of salmon calcitonin (50 U) three times a week for 12 months. Fifty patients (experiment Ⅱ group) received subcutaneous injection of salmon calcitonin (100 U) three times a week for 12 months. At the same time, both of them received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 μg qn for 12 months. The control group only received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 μg qn for 12 months. The levels of bone mass density (BMD) of the lumbar spine and femoral neck, serum intact parathyroid hormone (iPTH), osteocatcin (OC), calcium, phosphorus, alkaline phosphatase (ALP) were assessed at baseline and then again after 3, 6 and 12 months of treatment.Results The values of BMD at the lumbar spine and femoral neck before the treatment were not significantly different from those 3, 6, and 12 months after the treatment in trial groups I and II (all P >0.05) and there were no significant differences in the BMD values at different time points between trial groups I and I1. In the control group, the BMD values at the lumbar spine and femoral neck 3, 6, and 12 months after the beginning of trial were significantly lower than

  8. [Drug therapy for osteoporosis associated with rheumatoid arthritis (calcitonin)].

    Science.gov (United States)

    Ide, M; Suzuki, Y

    2001-05-01

    Calcitonin (CT) inhibits osteoclastic bone resorption and also exhibits long-lasting analgestic action, probably mediating through intrinsic serotonin and opioid peptides. The injection form of eel and salmon CT is only available in Japan. There are a few RCT data regarding the effect of CT on osteoporosis associated with RA, the previous studies have shown its effectiveness in terms of maintaining or increasing bone mineral density in RA patients with or without corticosteroid therapy. RA patients with high turnover osteoporosis and back pain might be a good indication of CT therapy.

  9. [Effectiveness of intranasal salmon calcitonin treatment in postmenopausal osteoporosis].

    Science.gov (United States)

    Kopaliani, M

    2005-04-01

    The aim of this study was to assess clinical efficacy of intranasal salmon calcitonin (Miacalcic, Novartis pharma) treatment in women with established postmenopausal osteoporosis. 30 women of the main group with established postmenopausal osteoporosis(T-score salmon calcitonin: 200 IU daily for 2 months with subsequent pause of 2 months (3 cycles), 12 months in total. Age matched control group was formed by 25 postmenopausal women with similar clinical status. SOS (speed of sound) of cortical bone was measured in the middle of the tibia by ultrasound densitometer--Sound Scan Compact (Myriad-Israel). Patients of both groups received 500 mg Ca and 200 IU vit.D3 (CaD3 Nycomed) two times daily in the same regimen (two months treatment--two months pause). Our results showed that intranasal treatment with 200 IU daily effectively influence the back pain, reduces bone turnover and significantly increases cortical BMD. Significant changes were not observed in patients of the control group, who received only CaD3 Nycomed, that showed that Calcium and vitamin D supplementation is more effective for prevention of bone lose in postmenopausal women, rather for treatment of established osteoporosis.

  10. Localization and characterization of renal calcitonin receptors by in vitro autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Sexton, P.M.; Adam, W.R.; Moseley, J.M.; Martin, T.J.; Mendelsohn, F.A.

    1987-12-01

    Calcitonin receptors were identified in renal cortex and medulla using the radioligand /sup 125/I-salmon calcitonin. Microscopic localization of these receptors revealed binding over medullary and cortical thick ascending limb of the loop of Henle and in distal convoluted tubule. A number of receptor positive cells in the inner medulla were also identified. Characterization of the binding demonstrated a single class of high-affinity binding sites in both the medulla and the cortex with affinity constants of 0.74 +/- 0.09 x 10(9) M-1 and 0.32 +/- 0.05 x 10(9) M-1, respectively, and receptor concentrations of 205 +/- 45 fmol/mg protein and 453 +/- 54 fmol/mg protein, respectively. Competition for /sup 125/I-salmon calcitonin binding by a wide range of calcitonin analogs revealed a close correspondence between the reported biological potencies and activities in the current system. The localization of binding sites within the nephron corresponds to the reported localization of calcitonin-stimulated adenylate cyclase activity and suggests that the receptor mediated actions of calcitonin in the kidney utilize cyclic AMP as a second messenger. In addition, the microscopic identification of specific calcitonin receptors helps the delineation of direct actions of this hormone from those which are indirect.

  11. Calcitonin-Induced Effects on Amniotic Fluid-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Caterina Morabito

    2015-05-01

    Full Text Available Background/Aims: Mesenchymal stem cells from human amniotic fluid (huAFMSCs can differentiate into multiple lineages and are not tumorigenic after transplantation, making them good candidates for therapeutic purposes. The aim was to determine the effects of calcitonin on these huAFMSCs during osteogenic differentiation, in terms of the physiological role of calcitonin in bone homeostasis. Methods: For huAFMSCs cultured under different conditions, we assayed: expression of the calcitonin receptor, using immunolabelling techniques; proliferation and osteogenesis, using colorimetric and enzymatic assays; intracellular Ca2+ and cAMP levels, using videomicroscopy and spectrophotometry. Results: The calcitonin receptor was expressed in proliferating and osteo-differentiated huAFMSCs. Calcitonin triggered intracellular Ca2+ increases and cAMP production. Its presence in cell medium also induced dose-dependent inhibitory effects on proliferation and increased osteogenic differentiation of huAFMSCs, as also indicated by enhancement of specific markers and alkaline phosphatase activity. Conclusions: These data show that huAFMSCs represent a potential osteogenic model to study in-vitro cell responses to calcitonin (and other members of the calcitonin family. This leads the way to the opening of new lines of research that will add new insight both in cell therapies and in the pharmacological use of these molecules.

  12. Radionuclide conjugates of calcitonin for imaging bone disease and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Greenland, William Edward Peverell

    2002-07-01

    Salmon calcitonin (sCt) is a peptide with a higher affinity for human calcitonin receptors (hCtR) than human calcitonin. It has been used for treating osteoporosis, Paget's disease and bone pain. High levels of hCtRs are expressed on osteoclasts, bone metastases and primary breast and prostate cancers. The peptide was chosen for radiolabelling as a possible imaging agent. Direct labelling with {sup 99m}Tc via simultaneous reduction of the indigenous disulfide bond and {sup 99m}TcO{sub 4}{sup -} (VII) with the water soluble phenyl phosphine (TPPDS) was performed. The radiolabelled peptide was not suitable for use as a radiopharmaceutical due to the heterogeneity of the product as observed by reverse phase HPLC and due to poor binding to the human breast cancer cell line MCF7. The electospray MS suggested a {sup 99}Tc-TPPDS (III) core instead of the expected {sup 99}Tc=O (V) core. Normal sCt has 3 conjugatible primary amines leading to a mixture of 8 possible products. A sCt analogue (sCtA) with a single primary amine was produced and conjugated to the chelator TETA to produce a single conjugated species. The sCtA-TETA was labelled with cold Cu and characterised by electospray MS. The monodentate ligand Hynic was synthesised directly into the peptide using N-{alpha}-Fmoc-N-{epsilon}-(Hynic-Boc)-Lys a novel orthogonally protected amino acid. The peptide was labelled with {sup 99m}Tc with tricine coligands. The radiolabelled peptide produced a single peak as observed by reverse phase HPLC and bound to MCF7 cell in a specific manner. The electospray MS suggested that one of the tricine coligands is lost due to the heating effect and possibly replaced by an adjacent histidine acting as a ternary ligand. The sCtLys{sup 18}-Hynic{sup 99m}Tc(tricine){sub 2} labelled peptide is the lead radiolabelled peptide and could be used for a normal biodistribution animal study, followed by clinical evaluation in humans. (author)

  13. [Effect of calcitonin, somatostatin and cimetidine on stress ulcer in rats].

    Science.gov (United States)

    Jakesz, R; Hofbauer, F; Lehr, L; Schiessel, R

    1978-05-01

    The prophylactic effect of calcitonin, somatostatin and cimetidine on stress ulcer formation in rats was investigated in two stress models: restraint + ketamin (4 h) and hypovolemia (4 h). The basis of the comparative study was a 70% inhibition of acid secretion for 4 h in pyloric ligated animals. This was achieved with 1000 microgram/kg somatostatin s.c., 10 microgram/kg calcitonin s.c., and 2 X 100 mumol/kg cimetidine s.c. In restraint stress and ketamin with calcitonin and cimetidine a significantly lower frequency of gastric lesions was found than with somatostatin. The most potent substance in hypovolemia was calcitonin, with a significant difference in the frequency of mucosal lesions to the groups with cimetidine and somatostatin.

  14. Calcitonin-negative primary neuroendocrine tumor of the thyroid (nonmedullary) in a dog

    Science.gov (United States)

    Arias, E.A. Soler; Castillo, V.A.; Aristarain, M.E. Caneda

    2016-01-01

    The Calcitonin-negative neuroendocrine tumor of the thyroid (CNNET) or “nonmedullary” in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of expression for calcitonin. An Argentine dogo bitch showed a solid, compact thyroid tumor, which was IHC negative for the expression of calcitonin, carcinoembryonic antigen, thyroglobulin and S100 protein, and positive for synaptophysin and cytokeratin AE1-AE3. The Ki-67 proliferation index was low. We cite this case not only because it is the first case report of calcitonin-negative primary neuroendocrine tumor of the thyroid in dogs but also because we want to highlight the diagnostic importance of IHC in this regard. PMID:27928520

  15. Involvement of calcitonin gene-related peptide in migraine

    DEFF Research Database (Denmark)

    Lassen, L H; Jacobsen, V B; Haderslev, P A

    2008-01-01

    mug/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V (mean)) in the middle cerebral artery (MCA), as well as the heart......Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (halphaCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of halphaCGRP (2...

  16. Calcitonin gene-related peptide in cervicogenic headache

    DEFF Research Database (Denmark)

    Frese, Amalie; Schilgen, M; Edvinsson, L

    2005-01-01

    Trigeminovascular activation is involved in the pathophysiology of migraine and cluster headache. The marker evaluated best for trigeminovascular activation is calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown whether trigeminovascular activation plays any role...... in cervicogenic headache (CEH). The objective of this study was to investigate CGRP plasma levels in CEH patients in relation to headache state. To compare plasma CGRP levels between the peripheral and the cranial circulation. Blood from both external jugular veins and from the antecubital vein was drawn from 11...... patients with CEH. Plasma CGRP levels were measured by radioimmunoassay. No difference was found between CGRP levels assessed on days with and without headache. There was no difference between CGRP levels from the symptomatic and the asymptomatic external jugular vein and the antecubital vein...

  17. False positive results using calcitonin as a screening method for medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Rafael Loch Batista

    2013-01-01

    Full Text Available The role of serum calcitonin as part of the evaluation of thyroid nodules has been widely discussed in literature. However there still is no consensus of measurement of calcitonin in the initial evaluation of a patient with thyroid nodule. Problems concerning cost-benefit, lab methods, false positive and low prevalence of medullary thyroid carcinoma (MTC are factors that limit this approach. We have illustrated two cases where serum calcitonin was used in the evaluation of thyroid nodule and rates proved to be high. A stimulation test was performed, using calcium as secretagogue, and calcitonin hyper-stimulation was confirmed, but anatomopathologic examination did not evidence medullar neoplasia. Anatomopathologic diagnosis detected Hashimoto thyroiditis in one case and adenomatous goiter plus an occult papillary thyroid carcinoma in the other one. Recommendation for routine use of serum calcitonin in the initial diagnostic evaluation of a thyroid nodule, followed by a confirming stimulation test if basal serum calcitonin is showed to be high, is the most currently recommended approach, but questions concerning cost-benefit and possibility of diagnosis error make the validity of this recommendation discussible.

  18. Low-Level Laser Therapy and Calcitonin in Bone Repair: Densitometric Analysis

    Directory of Open Access Journals (Sweden)

    Tatiana Pinto Ribeiro

    2012-01-01

    Full Text Available The aim of this work was to evaluate the association of low-level laser therapy (LLLT, 830 nm and calcitonin in bone repair considering that bone healing remains a challenge to health professionals. Calcitonin has antiosteoclastic action and LLLT is a treatment that uses low-level lasers or light-emitting diodes to alter cellular function. Both are used to improve bone healing. Densitometry is a clinical noninvasive valuable tool used to evaluate bone mineral density (BMD. Sixty male rats were submitted to bone defect with a trephine bur, randomly divided into four groups of 15 animals each: control (C; synthetic salmon calcitonin (Ca; LLLT (La; LLLT combined with calcitonin (LaCa. Animals from Ca and LaCa received 2 UI/Kg synthetic salmon calcitonin intramuscularly on alternate days after surgery. Animals from groups La and LaCa were treated with infrared LLLT (830 nm, 10 mW, 20 J/cm2, 6 s, contact mode. Five animals from each group were euthanized 7, 14, and 21 days after surgery and bone defects were analyzed by densitometry. Statistical analysis showed a significant difference in BMD values in LaCa group at 7 and 21 days (=0,005. The results of the densitometric study showed that LLLT (830 nm combined with calcitonin improved bone repair.

  19. The Inhibitory Effect of Salmon Calcitonin on Tri-Iodothyronine Induction of Early Hypertrophy in Articular Cartilage

    OpenAIRE

    Pingping Chen-An; Kim Vietz Andreassen; Kim Henriksen; Yadong Li; Morten Asser Karsdal; Anne-Christine Bay-Jensen

    2012-01-01

    OBJECTIVE: Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the ...

  20. MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Yang Kui

    2008-09-01

    Full Text Available Abstract Background Dysregulated expression and splicing of cell adhesion marker CD44 is found in many types of cancer. In prostate cancer (PC specifically, the standard isoform (CD44s has been found to be downregulated compared with benign tissue whereas predominant variant isoform CD44v7-10 is upregulated. Mitogen-activated protein kinase pathways and paracrine calcitonin are two common factors linked to dysregulated expression and splicing of CD44 in cancer. Calcitonin has been found to increase proliferation and invasion in PC acting through the protein kinase A pathway. Methods In androgen-independent PC with known high CD44v7-10 expression, CD44 total and CD44v7-10 RNA or protein were assessed in response to exogenous and endogenous calcitonin and to inhibitors of protein kinase A, MEK, JNK, or p38 kinase. Benign cells and calcitonin receptor-negative PC cells were also tested. Results MEK or p38 but not JNK reduced CD44 total RNA by 40%–65% in cancer and benign cells. Inhibition of protein kinase A reduced CD44 total and v7-10 protein expression. In calcitonin receptor-positive cells only, calcitonin increased CD44 variant RNA and protein by 3 h and persisting to 48 h, apparently dependent on an uninhibited p38 pathway. Cells with constitutive CT expression showed an increase in CD44v7-10 mRNA but a decrease in CD44 total RNA. Conclusion The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing.

  1. Calcitonin Receptor AluI (rs1801197) and Taq1 Calcitonin Genes Polymorphism in 45-and Over 45-year-old Women and their Association with Bone Density

    Science.gov (United States)

    Dehghan, Morteza; Pourahmad-Jaktaji, Razieh; Farzaneh, Zarghampoor

    2016-01-01

    Purpose: Calcitonin receptor gene has also a polymorphism which is associated with bone mass density. This study evaluates the association between calcitonin receptor AluI (rs1801197) and Taq1 calcitonin genes polymorphism with bone density rate. Methods: In this descriptive-analytical study in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenol– chloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. Results: The genotypic distribution of polymorphism AluI for TT, TC, and CC genotypes in control group was 31.4%, 38.6%, and 30% and in patients 25.4%, 55.4%, and 19.2%, respectively. There was no significant difference in polymorphism AluI between patients and control group and no significant association was found between this gene and bone density rate (P > 0.05). All patients and the individuals in the control group exhibited tt genotype for TaqI calcitonin gene and no significant association was found between these participants and osteoporosis. Conclusion: There was no association between two polymorphisms and osteoporosis, and between polymorphism of these two genes and osteoporosis development rate in the participants. PMID:27708484

  2. Eel calcitonin binding site distribution and antinociceptive activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guidobono, F.; Netti, C.; Sibilia, V.; Villa, I.; Zamboni, A.; Pecile, A.

    1986-03-01

    The distribution of binding site for (/sup 125/I)-eel-calcitonin (ECT) to rat central nervous system, studied by an autoradiographic technique, showed concentrations of binding in the diencephalon, the brain stem and the spinal cord. Large accumulations of grains were seen in the hypothalamus, the amygdala, in the fasciculus medialis prosencephali, in the fasciculus longitudinalis medialis, in the ventrolateral part of the periventricular gray matter, in the lemniscus medialis and in the raphe nuclei. The density of grains in the reticular formation and in the nucleus tractus spinalis nervi trigemini was more moderate. In the spinal cord, grains were scattered throughout the dorsal horns. Binding of the ligand was displaced equally by cold ECT and by salmon CT(sCT), indicating that both peptides bind to the same receptors. Human CT was much weaker than sCT in displacing (/sup 125/I)-ECT binding. The administration of ECT into the brain ventricles of rats dose-dependently induced a significant and long-lasting enhancement of hot-plate latencies comparable with that obtained with sCT. The antinociceptive activity induced by ECT is compatible with the topographical distribution of binding sites for the peptide and is a further indication that fish CTs are active in the mammalian brain.

  3. Radioimmunoassay of calcitonin in unextracted human serum: a sensitive method

    Energy Technology Data Exchange (ETDEWEB)

    Emmertsen, K.; Marqversen, J.; Jensen, F.T.; Hansen, H.H. (Kommunehospitalet, Copenhagen (Denmark))

    1982-11-01

    A sensitive sequential direct radioimmunoassay of calcitonin (CT) is described. Human synthetic monomer CT was used for /sup 125/I-labelling. The antibody was directed against mid-portion and C-terminal parts of the human CT molecule. No significant cross reactivity with salmon or porcine CT was found. Separation of free from antibody-bound /sup 125/I-labelled CT was performed using a double antibody-polyethyleneglycol mixture. Dilution curves of sera from normal controls and patients with medullary thyroid carcinoma (MCT) were parallel to the standard curve. The intraassay coefficients of variation (CV) were 6% and 3% at serum concentrations of 90 and 230 ng/l respectively. The interassay CV were 13% and 10% at mean serum CT concentrations of 50 and 210 ng/l respectively. The lower limit of detection was 20 ng/l. Thirty-one healthy controls had serum CT levels in the range of 35-135 ng/l. Elevated basal serum CT concentrations were found in 11 patients with MCT and the serum concentrations increased markedly after pentagastrin stimulation. Subsequent thyroidectomy in eight of the 11 patients with MCT reduced basal serum CT levels, in six to within the reference range for normals.

  4. Mucoadhesive intestinal devices for oral delivery of salmon calcitonin.

    Science.gov (United States)

    Gupta, Vivek; Hwang, Byeong Hee; Lee, Joohee; Anselmo, Aaron C; Doshi, Nishit; Mitragotri, Samir

    2013-12-28

    One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈75% cumulative drug released in 5h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈52-fold (pharmacokinetic) and ≈44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.

  5. Delivery of salmon calcitonin using a microneedle patch.

    Science.gov (United States)

    Tas, Cetin; Mansoor, Saffar; Kalluri, Haripriya; Zarnitsyn, Vladimir G; Choi, Seong-O; Banga, Ajay K; Prausnitz, Mark R

    2012-02-28

    Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL min). T(max) (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.

  6. In vivo iontophoretic delivery of salmon calcitonin across microporated skin.

    Science.gov (United States)

    Vemulapalli, Viswatej; Bai, Yun; Kalluri, Haripriya; Herwadkar, Anushree; Kim, Hyun; Davis, Shawn P; Friden, Phil M; Banga, Ajay K

    2012-08-01

    The purpose of this study was to determine the effect of microneedle (MN) technology and its combination with iontophoresis (ITP) on the in vivo transdermal delivery of salmon calcitonin (sCT). Maltose MNs (500 µm) were used to porate skin prior to application of the drug, with or without ITP. Micropores created by maltose MNs were characterized by histological sectioning and calcein imaging studies, which indicated uniformity of the created micropores. In vivo studies were performed in hairless rats to assess the degree of enhancement achieved by ITP (0.2 mA/cm² for 1 h), MNs (81 MNs), and their combination. In vivo studies indicate a serum maximal concentration of 0.61 ± 0.42 ng/mL, 1.79 ± 0.72 ng/mL, and 5.51 ± 0.32 ng/mL for ITP, MNs, and combination treatment, respectively. MN treatment alone increased serum concentration 2.5-fold and the combination treatment increased the concentration ninefold as compared with iontophoretic treatment alone. Combination treatment of ITP and MNs resulted in the highest delivery of sCT and therapeutic levels were achieved within 5 min of administration.

  7. Rapid calcitonin response to experimental hypercalcemia in healthy horses.

    Science.gov (United States)

    Rourke, K M; Kohn, C W; Levine, A L; Rosol, T J; Toribio, R E

    2009-05-01

    Calcium has important physiological functions, and disorders of calcium homeostasis are frequent in horses. We have made important progress understanding equine calcium homeostasis; however, limited information on equine calcitonin (CT) is available, in part because of the lack of validated CT assays. To determine the CT response to high ionized calcium (Ca(2+)) concentrations in healthy horses, we induced hypercalcemia in 10 healthy horses using a calcium gluconate 23% solution (5mg/kg; 120 mL/500 kg horse) infused over 4 min. Four horses were infused with 120 mL of 0.9% NaCl and used as controls. We validated a human-specific CT radioimmunoassay for use in horses. Serum Ca(2+) concentrations increased from 6.2+/-0.3mg/dL to 9.9+/-0.5mg/dL (4 min; Pequine thyroid gland C-cell responds quickly to changes in extracellular Ca(2+) concentrations by secreting large quantities of CT into the systemic circulation, indicating that CT is important in equine calcium homeostasis. The human CT radioimmunoassay can be used to measure changes in equine CT.

  8. Does salmon calcitonin cause cancer? A review and meta-analysis.

    Science.gov (United States)

    Wells, G; Chernoff, J; Gilligan, J P; Krause, D S

    2016-01-01

    Recently an association between the use of calcitonin and cancer has been postulated. We reviewed the biological rationale and performed an additional analysis of historical data with respect to the possibility. An association cannot be excluded, but the relationship is weak and causality is unlikely. The purpose of the present study is to review the strength of association and likelihood of a causal relationship between use of calcitonin and cancer. We reviewed the evidence for this association, including the molecular signaling mechanisms of calcitonin, preclinical data, an "experiment of nature," and the results of a previous meta-analysis which showed a weak association. We performed an additional meta-analysis to incorporate the data from a novel investigational oral formulation of salmon calcitonin. Review of the literature did not identify a cellular signaling mechanism of action which might account for a causal relationship or toxicologic or postmarketing data to support the thesis. Additional clinical results incorporated into previous meta-analyses weakened but did not completely negate the possibility of association. A causal association between calcitonin use and malignancy is unlikely, as there is little biological plausibility. The preponderance of nonclinical and clinical evidence also does not favor a causal relationship.

  9. Low cytotoxic elastic niosomes loaded with salmon calcitonin on human skin fibroblasts.

    Science.gov (United States)

    Manosroi, Aranya; Chankhampan, C; Ofoghi, H; Manosroi, W; Manosroi, J

    2013-01-01

    A low cytotoxic elastic niosomal formulation loaded with salmon calcitonin was developed. The elastic niosomes were prepared from Tween 61 mixed with cholesterol at various concentrations of the edge activators (sodium cholate (NaC) and sodium deoxycholate (NaDC); 0.25, 0.5, 2.5, 5 and 10% mole) or ethanol (10-30% v/v). The effects of the niosomal concentrations (5, 10 and 20 mM) and phosphate buffer at pH 7.0 (5, 10, 20 and 30 mM) on the physical characteristics of niosomes were investigated. The 5 mM elastic niosomes in 5 mM phosphate buffer containing calcitonin 0.22 mg/mL gave the highest elasticity (deformability index (DI)) at 6.79 ± 2.03 determined by the extrusion method. The blank elastic niosomes comprised 2.5% mole NaDC, 5% mole NaC or 20% v/v ethanol showed the highest elasticity. The 5% mole NaC elastic niosomes loaded with calcitonin gave the highest DI (21.59 ± 0.91) and percentages of calcitonin entrapment efficiency (60.11 ± 4.98). This study has demonstrated that this NaC elastic niosome did not only reduce the cytotoxicity of the loaded calcitonin but also gave superior cell viability to the ethanolic elastic niosome as well.

  10. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth

    Institute of Scientific and Technical Information of China (English)

    Mona A Abbassy; Ippei Watari; Ahmed S Bakry; Takashi Ono; Ali H Hassan

    2016-01-01

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C1D group (normal rats injected with calcitonin and vitamin D3), the diabetic C1D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C1D groups using a single dose of 60 mg?kg–1 body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C1D and diabetic C1D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C1D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties.

  11. Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats

    DEFF Research Database (Denmark)

    Feigh, M; Andreassen, K V; Neutzsky-Wulff, A V

    2012-01-01

    Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male Zucker diabetic fatty...... (ZDF) rats, a model of type 2 diabetes....

  12. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes

    DEFF Research Database (Denmark)

    Sondergaard, B C; Wulf, H; Henriksen, K

    2006-01-01

    chain reaction (RT-PCR). In bovine articular cartilage explants, cartilage degradation was investigated by release of C-terminal telopeptides of collagen type II (CTX-II), induced by tumor necrosis factor-alpha (TNF-alpha) [20 ng/ml] and oncostatin M (OSM) [10 ng/ml], with salmon calcitonin [0.......0001-1 microM]. In vivo, cartilage degradation was investigated in ovariectomized (OVX) rats administered with oral calcitonin [2 mg/kg calcitonin] for 9 weeks. RESULTS: The calcitonin receptor was identified in articular chondrocytes by immunohistochemistry and RT-PCR. Calcitonin concentration......-dependently increased cAMP levels in isolated chondrocytes. Explants cultured with TNF-alpha and OSM showed a 100-fold increase in CTX-II release compared to vehicle-treated controls (Pprotection...

  13. Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation.

    Science.gov (United States)

    Woodrow, Janine P; Sharpe, Christopher J; Fudge, Neva J; Hoff, Ana O; Gagel, Robert F; Kovacs, Christopher S

    2006-09-01

    The maternal skeleton rapidly demineralizes during lactation to provide calcium to milk, responding to the stimuli of estrogen deficiency and mammary-secreted PTH-related protein. We used calcitonin/calcitonin gene-related peptide-alpha (Ctcgrp) null mice to determine whether calcitonin also modulates lactational mineral metabolism. During 21 d of lactation, spine bone mineral content dropped 53.6% in Ctcgrp nulls vs. 23.6% in wild-type (WT) siblings (P bone mineral content returned fully to baseline in 18.1 d in Ctcgrp null vs. 13.1 d in WT (P protect the maternal skeleton against excessive resorption and attendant fragility during lactation and reveal that the postweaning skeleton has the remarkable ability to rapidly recover even from losses of over 50% of skeletal mineral content.

  14. Quantitative Structure-Activity Relationships and Docking Studies of Calcitonin Gene-Related Peptide Antagonists

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range...... of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression....... The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model...

  15. Skeletal blood flow in Paget's disease of bone and its response to calcitonin therapy.

    Science.gov (United States)

    Wootton, R; Reeve, J; Spellacy, E; Tellez-Yudilevich, M

    1978-01-01

    1. Blood flow to the skeleton was measured by the 18F clearance method of Wooton, Reeve & Veall (1976) in 24 patients with untreated Paget's disease. In every patient but one, resting skeletal blood flow was increased. There was a significant positive correlation between skeletal blood flow and serum alkaline phosphatase and between skeletal blood flow and urinary total hydroxyproline excretion. 2. Fourteen patients were re-studied after they had received short-term (7 days or less) or long-term (7 weeks or more) calcitonin. Skeletal blood flow, alkaline phosphatase and urinary hydroxy-proline excretion fell towards normal in every case. There was some evidence from the short-term studies that calcitonin produced a more rapid fall in skeletal blood flow than in alkaline phosphatase. 3. Glomerular filtration rate appeared to increase transiently in response to calcitonin.

  16. The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

    Directory of Open Access Journals (Sweden)

    Pingping Chen-An

    Full Text Available OBJECTIVE: Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants. METHODS: Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13, by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers. RESULTS: Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05, of cartilage turnover (p<0.05, and of CTR (p<0.01. Salmon, but not human, calcitonin induced cAMP release (p<0.001. Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05. CONCLUSIONS: T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.

  17. Quality analysis of salmon calcitonin in a polymeric bioadhesive pharmaceutical formulation: sample preparation optimization by DOE.

    Science.gov (United States)

    D'Hondt, Matthias; Van Dorpe, Sylvia; Mehuys, Els; Deforce, Dieter; DeSpiegeleer, Bart

    2010-12-01

    A sensitive and selective HPLC method for the assay and degradation of salmon calcitonin, a 32-amino acid peptide drug, formulated at low concentrations (400 ppm m/m) in a bioadhesive nasal powder containing polymers, was developed and validated. The sample preparation step was optimized using Plackett-Burman and Onion experimental designs. The response functions evaluated were calcitonin recovery and analytical stability. The best results were obtained by treating the sample with 0.45% (v/v) trifluoroacetic acid at 60 degrees C for 40 min. These extraction conditions did not yield any observable degradation, while a maximum recovery for salmon calcitonin of 99.6% was obtained. The HPLC-UV/MS methods used a reversed-phase C(18) Vydac Everest column, with a gradient system based on aqueous acid and acetonitrile. UV detection, using trifluoroacetic acid in the mobile phase, was used for the assay of calcitonin and related degradants. Electrospray ionization (ESI) ion trap mass spectrometry, using formic acid in the mobile phase, was implemented for the confirmatory identification of degradation products. Validation results showed that the methodology was fit for the intended use, with accuracy of 97.4+/-4.3% for the assay and detection limits for degradants ranging between 0.5 and 2.4%. Pilot stability tests of the bioadhesive powder under different storage conditions showed a temperature-dependent decrease in salmon calcitonin assay value, with no equivalent increase in degradation products, explained by the chemical interaction between salmon calcitonin and the carbomer polymer.

  18. Type II Turn of Receptor-bound Salmon Calcitonin Revealed by X-ray Crystallography.

    Science.gov (United States)

    Johansson, Eva; Hansen, Jakob Lerche; Hansen, Ann Maria Kruse; Shaw, Allan Christian; Becker, Peter; Schäffer, Lauge; Reedtz-Runge, Steffen

    2016-06-24

    Calcitonin is a peptide hormone consisting of 32 amino acid residues and the calcitonin receptor is a Class B G protein-coupled receptor (GPCR). The crystal structure of the human calcitonin receptor ectodomain (CTR ECD) in complex with a truncated analogue of salmon calcitonin ([BrPhe(22)]sCT(8-32)) has been determined to 2.1-Å resolution. Parallel analysis of a series of peptide ligands showed that the rank order of binding of the CTR ECD is identical to the rank order of binding of the full-length CTR, confirming the structural integrity and relevance of the isolated CTR ECD. The structure of the CTR ECD is similar to other Class B GPCRs and the ligand binding site is similar to the binding site of the homologous receptors for the calcitonin gene-related peptide (CGRP) and adrenomedulin (AM) recently published (Booe, J. M., Walker, C. S., Barwell, J., Kuteyi, G., Simms, J., Jamaluddin, M. A., Warner, M. L., Bill, R. M., Harris, P. W., Brimble, M. A., Poyner, D. R., Hay, D. L., and Pioszak, A. A. (2015) Mol. Cell 58, 1040-1052). Interestingly the receptor-bound structure of the ligand [BrPhe(22)]sCT(8-32) differs from the receptor-bound structure of the homologous ligands CGRP and AM. They all adopt an extended conformation followed by a C-terminal β turn, however, [BrPhe(22)]sCT(8-32) adopts a type II turn (Gly(28)-Thr(31)), whereas CGRP and AM adopt type I turns. Our results suggest that a type II turn is the preferred conformation of calcitonin, whereas a type I turn is the preferred conformation of peptides that require RAMPs; CGRP, AM, and amylin. In addition the structure provides a detailed molecular explanation and hypothesis regarding ligand binding properties of CTR and the amylin receptors.

  19. A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial.

    Science.gov (United States)

    Binkley, Neil; Bolognese, Michael; Sidorowicz-Bialynicka, Anna; Vally, Tasneem; Trout, Richard; Miller, Colin; Buben, Christine E; Gilligan, James P; Krause, David S

    2012-08-01

    The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2  mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000  mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis.

  20. Evaluation of bone targeting salmon calcitonin analogues in rats developing osteoporosis and adjuvant arthritis.

    Science.gov (United States)

    Bhandari, Krishna H; Asghar, Waheed; Newa, Madhuri; Jamali, Fakhreddin; Doschak, Michael R

    2015-01-01

    Synthetic analogues of the peptide hormone calcitonin have been used in medicine as biologic drug therapies for decades, to treat pathological conditions of excessive bone turnover, such as osteoporosis, where more bones are removed than replaced during bone remodeling. Osteoporosis and other chronic skeletal diseases, including inflammatory arthritis, exact a substantial and growing toll on aging populations worldwide however they respond poor to synthetic biologic drug therapy, due in part to the rapid half-life of elimination, which for calcitonin is 43 minutes. To address those shortcomings, we have developed and synthesized bone-targeting variants of calcitonin as a targeted drug delivery strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in highly specific reaction conditions. To evaluate their in vivo efficacy, bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and dose escalation was performed in female rats developing Osteoporosis. The bone-targeting calcitonin analogues were also tested in a separate cohort of male rats developing adjuvant-induced arthritis. Ovariectomized female rats developing Osteoporosis were administered daily sub-cutaneous injection of analogues equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis was developed in male rats by administering Mycobacterium butyricum through tail base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg of calcitonin was administered and the rats were measured for visible signs of inflammation to a 21 day endpoint. In both studies, the effect of drug intervention upon bone volume and bone mineral density (BMD) was assessed by measuring the trabecular bone volume percentage and BMD at the proximal tibial metaphysis using in vivo micro-computed tomography. With dose escalation studies, only bone targeting analogue dosed groups

  1. An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Sekiguchi Miho

    2008-12-01

    Full Text Available Abstract Background Calcitonin is used as a treatment to reduce the blood calcium concentration in hypercalcemia and to improve bone mass in osteoporosis. An analgesic effect of calcitonin has been observed and reported in clinical situations. Ovariectomaized (OVX rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopousal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study. Methods We assessed the antinociceptive effects of calcitonin in an ovariectomized (OVX rat model, which exhibit osteoporosis and hyperalgesia, using the immunohistochemical method. Fifteen rats were ovariectomized bilaterally, and ten rats were received the same surgery expected for ovariectomy as a sham model. We used five groups: the OVX-CT (n = 5, the sham-CT (n = 5, and the OVX-CT-pcpa (n = 5 groups recieved calcitonin (CT: 4 U/kg/day, while OVX-vehi (n = 5 and the sham-vehi (n = 5 groups received vehicle subcutaneously 5 times a week for 4 weeks. The OVX-CT-pcpa-group was given traperitoneal injection of p-chlorophenylalanine (pcpa; an inhibitor of serotonin biosynthesis (100 mg/kg/day in the last 3 days of calcitonon injection. Two hours after 5% formalin (0.05 ml subcutaneously into the hind paw, the L5 spinal cord were removed and the number of Fos-immunoreactive (ir neurons were evaluated using the Mann-Whitney-U test. Results The numbers of Fos-ir neurons in the OVX-CT and sham-CT groups were significantly less than in the OVX-vehi and sham-vehi groups, respectively (p = 0.0090, p = 0.0090. The number of Fos-ir neurons in the OVX-CT-pcpa-group was significantly more than that of the OVX-CT-group (p = 0.0283, which means pcpa inhibits calcitonin induced reduction of c-Fos production. Conclusion The results in this study demonstrated that 1 the increase of c-Fos might be related to hyperalgesia in OVX-rats. 2 Calcitonin has

  2. [Rational (injection) of calcitonin for stimulation of the mandibular reparative regeneration].

    Science.gov (United States)

    Shvyrkov, M B

    2011-01-01

    This investigation permit to detect, that first resorption stage of the mandible reparative regeneration terminats after fracture 5 days later. Calcitonine injection during 5 days after fracture i.e. in paratiroid hormone dependent stage distorts normal reparative process. Rats with traumatic osteomielitis become 1.5 times more and rats with normal regeneration become 3 times less. Injection calcitonine in KT-dependent stage, i.e. in 6-11 days after fracture increases quantity of rats with normal regeneration in 7 times and decreases quantity animals with traumatic osteomielitis on 50%. There's recommendation to inject KT from 6 days after trauma.

  3. Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

    DEFF Research Database (Denmark)

    Edvinsson, L; Ahnstedt, H; Larsen, R;

    2014-01-01

    Calcitonin gene-related peptide (CGRP) and its receptor are widely distributed within the circulation and the mechanism behind its vasodilation not only differs from one animal species to another but is also dependent on the type and size of vessel. The present study examines the nature of CGRP......-induced vasodilation, characteristics of the CGRP receptor antagonist telcagepant and localization of the key components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human subcutaneous arteries....

  4. Calcitonin Gene-Related Peptide in Tension-Type Headache

    Directory of Open Access Journals (Sweden)

    M. Ashina

    2002-01-01

    Full Text Available In the last 10 years there has been increasing interest in the role of calcitonin gene-related peptide (CGRP in primary headaches. Tension-type headache is one of the most common and important types of primary headaches, and ongoing nociception from myofascial tissues may play an important role in the pathophysiology of this disorder. CGRP sensory fibers are preferentially located in the walls of arteries, and nerve fibers containing CGRP accompany small blood vessels in human cranial muscles. It is well established that nociception may lead to release of CGRP from sensory nerve endings and from central terminals of sensory afferents into the spinal cord. It has also been shown that density of CGRP fibers around arteries is increased in persistently inflamed muscle. These findings indicate that ongoing activity in sensory neurons in the cranial muscles may be reflected in changes of plasma levels of neuropeptides in patients with chronic tension-type headache. To explore the possible role of CGRP in tension-type headache, plasma levels of CGRP were measured in patients with chronic tension-type headache. This study showed that plasma levels of CGRP are normal in patients and unrelated to headache state. However, the findings of normal plasma levels of CGRP do not exclude the possibility that abnormalities of this neuropeptide at the neuronal or peripheral (pericranial muscles levels play a role in the pathophysiology of tension-type headache. Investigation of CGRP in other compartments with new sensitive methods of analysis is necessary to clarify its role in tension-type headache.

  5. Iodine-123 salmon calcitonin, an imaging agent for calcitonin receptors: synthesis, biodistribution, metabolism and dosimetry in humans

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J.; Kettle, A.G.; Leak, A.; O`Doherty, M.J. [Department of Nuclear Medicine, Kent and Canterbury Hospital, Canterbury (United Kingdom); Puncher, M.R.B.; George, S.; Dorsch, S.; Naylor, L.H. [Department of Biosciences, University of Kent, Canterbury (United Kingdom)

    1998-02-01

    A modified chloramine-T method was used to label a pharmaceutical form of salmon calcitonin (SCT) with iodine-123. Labelling can be performed within 5 min including purification, resulting in >95% radiochemical purity and 70% yield. Digestion analysis shows labelling with two iodine atoms on the tyrosine residue. A Chinese hamster ovary cell-based assay showed that the receptor binding and activation were not impaired by the labelling. Biodistribution in mice was similar to that of commercially available mono-iodinated {sup 125}I-labelled SCT, kidney being the principal target organ. Evaluation in three patients previously diagnosed as having Paget`s disease (injected with 37 MBq [{sup 123}I]diiodotyrosyl{sup 22}-SCT, containing less than 4 IU hormone, imaged dynamically up to 0.5 h and at intervals up to 24 h) shows early uptake in liver, kidney and sites of known Paget`s disease but not in normal bone, and later uptake in thyroid and stomach. Blood clearance was fitted to a biexponential with half-lives of 3.4-7.4 min and 3-34 h. Radiation dosimetry was estimated using MIRDOSE 3. The highest doses (mean mGy/MBq) were to thyroid (6.8 x 10{sup -1}) and kidney (6.0 x 10{sup -2}), with a whole-body dose 3.0 x 10{sup -2}. High performance liquid chromatography analysis revealed that urinary radioactivity was mostly in the form of iodide and diiodotyrosine within minutes of injection, indicating rapid in vivo breakdown.(orig. /MG) (orig.) With 8 figs., 1 tab., 28 refs.

  6. C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

    Science.gov (United States)

    Nakazawa, Tadao; Cameselle-Teijeiro, José; Vinagre, João; Soares, Paula; Rousseau, Emmanuel; Eloy, Catarina; Sobrinho-Simões, Manuel

    2014-09-01

    In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery.

  7. Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule.

    Science.gov (United States)

    Mousa, Umut; Gursoy, Alptekin; Ozdemir, Handan; Moray, Gokhan

    2013-07-01

    Serum calcitonin is a tumor marker used in the diagnosis and follow-up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61-year-old female patient with known Hashimoto's thyroditis and an 8-mm hypoechoic nodule was presented with one previously benign fine-needle aspiration cytology (FNAC). On referral to our department, she had a moderately high-serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high-serum calcitonin levels.

  8. VIP and Calcitonin-Producing Pancreatic Neuroendocrine Tumor with Watery Diarrhea: Clinicopathological Features and the Effect of Somatostatin Analogue

    Directory of Open Access Journals (Sweden)

    Tomoya Kon

    2012-03-01

    Full Text Available Context Pancreatic neuroendocrine tumor (pNET secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial. Case report A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0- 100 pg/mL, and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL. There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable. Conclusion From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs.

  9. Acute effects of nasal salmon calcitonin on calcium and bone metabolism

    DEFF Research Database (Denmark)

    Thamsborg, G; Skousgaard, S G; Daugaard, H;

    1993-01-01

    Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood...

  10. Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement

    DEFF Research Database (Denmark)

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon;

    2015-01-01

    hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate...

  11. Evaluation of the analgesic effect of salmon calcitonin in metastatic bone pain

    Directory of Open Access Journals (Sweden)

    Mishra Seema

    2003-01-01

    Full Text Available Aim: To evaluate the efficacy of calcitonin in controlling metastatic bone pain. Materials and methods: Patients with bone metastases, with a numerical pain score greater than 4 wererandomized to receive calcitonin 200 IU subcutaneously 6 hourly for 48 hours (n= 10 or normal saline placebo (n = 10 . The parameters measured were the 11-point numerical pain score, ECOG functional capacity score, morphine consumption in 24 hours, duration of pain in 24 hours and subjective assessment of efficacy of treatment by a blinded investigator. Results: There was a statistically significant decrease in pain score at 48 hours (2 vs 6 and 7 days (3 vs 6 in the calcitonin arm as compared to the control arm. The reduction in duration of pain (3 vs 13 and improvement in ECOG (1.5 vs 2.5 score were also statistically significant. Adverse effects were nausea in 5 patients and vomiting in 3 patients on the day of calcitonin administration. This was controlled with antiemetics. There was no significant change in serum calcium level in either group.

  12. Iontophoresis significantly increases the trans-dentinal delivery of osteoprotegerin, alendronate, and calcitonin.

    Science.gov (United States)

    Kitchens, James A; Schwartz, Scott A; Schindler, William G; Hargreaves, Kenneth M

    2007-10-01

    The purpose of this study was to evaluate the delivery of alendronate, calcitonin, and osteoprotegerin (OPG) through human dentin by both diffusion and iontophoresis for the potential treatment of invasive cervical resorption. Radiolabeled alendronate, calcitonin, and OPG were added to the top of a split chamber device that contained 1-mm thick dentin disks devoid of a smear layer. Transdentinal movement of medicaments by either random diffusion or application of an iontophoretic current was measured by analysis of gamma emission of effluent fractions. In addition, calcitonin delivery was evaluated at differing magnitudes of current (0-4 mA) by using the aforementioned chamber. Diffusion of all 3 medicaments was minimal. In contrast, the application of a 3-mA iontophoretic gradient significantly increased delivery for all 3 compounds at 10-, 20-, and 30-minute intervals. In addition, a linear increase in permeability was seen for calcitonin as milliamperes were increased from 0 to 4 (r = 0.947), with more than a 100-fold increase in delivery observed with iontophoresis. Delivery of the tested medicaments by using iontophoresis might prove to be a useful technique for treatment of invasive cervical resorption.

  13. Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries

    NARCIS (Netherlands)

    L. Edvinsson (Lars); K.Y. Chan (Kayi); S. Eftekhari; E. Nilsson (Elisabeth); R. de Vries (René); H. Säveland (Hans); C.M.F. Dirven (Clemens); A.H.J. Danser (Jan)

    2010-01-01

    textabstractIntroduction: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. Materials and methods: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-in

  14. Effect of calcium carbonate combined with calcitonin on hypercalcemia in hemodialysis patients.

    Science.gov (United States)

    Wei, Yong; Kong, Xiang Lei; Li, Wen Bin; Wang, Zun Song

    2014-12-01

    This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin.

  15. Calcitonin treatment in osteoectasia with hyperphosphatasia (juvenile Paget's disease): radiographic changes after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Tueysuez, B. [Div. of Genetics and Teratology, Univ. of Istanbul (Turkey); Serencebey, Istanbul (Turkey); Mercimek, S.; Uenguer, S. [Dept. of Paediatrics, Univ. of Istanbul (Turkey); Deniz, M. [Dept. of Paediatrics, Haseki Hospital, Istanbul (Turkey)

    1999-11-01

    Osteoectasia with hyperphosphatasia is a rare skeletal disorder, characterised by demineralisation and expansion of tubular bones and elevated serum alkaline phosphatase. We present a girl diagnosed as having osteoectasia with hyperphosphatasia who had swelling of phalanges of both hands and motor retardation. She was treated with synthetic human calcitonin. Clinical and radiological findings showed remarkable improvement after 2 years' treatment. (orig.)

  16. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Thomsen, Lise L; Olesen, Jes

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine-...

  17. Randomised placebo-controlled trial on the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis.

    Science.gov (United States)

    Tafazal, Suhayl I; Ng, Leslie; Sell, Philip

    2007-02-01

    This is a double blind randomised controlled trial to assess the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis. The trial compared the outcome of salmon calcitonin nasal spray to placebo nasal spray in patients with MRI confirmed lumbar spinal stenosis. Lumbar spinal stenosis is one of the commonest conditions encountered by spine surgeons. It more frequently affects elderly patients and lumbar decompression has been used to treat the condition with variable success. Non operative measures have been investigated, but their success ranges from 15% to 43% in patients followed up for 1-5 years (Simotas in Clin Orthop 1(384):153-161, 2001). Salmon calcitonin injections have been investigated in previous trials and may have a treatment effect. Nasal salmon calcitonin has become available and if effective would have advantages over injections. Forty patients with symptoms of neurogenic claudication and MRI proven lumbar spinal stenosis were randomly assigned either nasal salmon calcitonin or placebo nasal spray to use for 4 weeks. This was followed by a 'washout' period of 6 weeks, and subsequent treatment with 6 weeks of nasal salmon calcitonin. Standard spine outcome measures including Oswestry disability index (ODI), low back outcome score, visual analogue score and shuttle walking test were administered at baseline, 4, 10 and 16 weeks. Twenty patients received nasal salmon calcitonin and twenty patients received placebo nasal spray. At 4 weeks post treatment there was no statistically significant difference in the outcome measures between the two groups. The change in ODI was a mean 1.3 points for the calcitonin group and 0.6 points for the placebo group (P = 0.51), the mean change in visual analogue score for leg pain was 10 mm in the calcitonin group and 0 mm in the placebo group (P = 0.51). There was no significant difference in walking distance between the two groups, with a mean improvement in walking distance of 21 m in the

  18. Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys.

    Science.gov (United States)

    Bello, Nicholas T; Kemm, Matthew H; Moran, Timothy H

    2008-07-01

    Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.

  19. Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density

    Directory of Open Access Journals (Sweden)

    Daripa M.

    2004-01-01

    Full Text Available The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD were compared to those of 17 normal individuals (C and of 9 patients with other forms of hypothyroidism (OH: 4 with hypothyroidism due to inborn errors of thyroid hormone synthesis and 5 with Hashimoto's thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+, calcitonin, and intact parathyroid hormone. Bone mineral density (BMD was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C = 1.29 ± 0.08 vs TD = 1.34 ± 0.03 vs OH = 1.34 ± 0.02 mmol/l; P < 0.05, and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 ± 5.8 vs TD = 6.6 ± 0.3 vs OH = 43.0 ± 13.4 ng/l. BMD values did not differ significantly between groups (L2-L4: C = 1.116 ± 0.02 vs TD = 1.109 ± 0.03 vs OH = 1.050 ± 0.04 g/cm². These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

  20. Calcitonin gene-related peptide induced migraine attacks in patients with and without familial aggregation of migraine

    DEFF Research Database (Denmark)

    Guo, Song; Christensen, Anne Francke; Liu, Marie Louise

    2017-01-01

    BACKGROUND: Calcitonin gene-related peptide provokes migraine attacks in 65% of patients with migraine without aura. Whether aggregation of migraine in first-degree relatives (family load) or a high number of risk-conferring single nucleotide polymorphisms contributes to migraine susceptibility...... to calcitonin gene-related peptide infusion in migraine patients is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and, therefore, migraine without aura patients with high family load would report more migraine attacks after calcitonin gene-related peptide infusion than...... patients with low family load. METHODS: We allocated 40 previously genotyped migraine without aura patients to receive intravenous infusion of 1.5 µg/min calcitonin gene-related peptide and recorded migraine attacks including headache characteristics and associated symptoms. Information of familial...

  1. Randomised placebo-controlled trial on the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis

    OpenAIRE

    Tafazal, Suhayl I.; Ng, Leslie; Sell, Philip

    2006-01-01

    This is a double blind randomised controlled trial to assess the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis. The trial compared the outcome of salmon calcitonin nasal spray to placebo nasal spray in patients with MRI confirmed lumbar spinal stenosis. Lumbar spinal stenosis is one of the commonest conditions encountered by spine surgeons. It more frequently affects elderly patients and lumbar decompression has been used to treat the condition with varia...

  2. Cloning of two members of the calcitonin-family receptors from stingray, Dasyatis akajei: possible physiological roles of the calcitonin family in osmoregulation.

    Science.gov (United States)

    Suzuki, Nobuo; Sekiguchi, Toshio; Satake, Honoo; Kato, Kanoko; Nishiyama, Yudai; Takahashi, Hideya; Danks, Janine A; Martin, T John; Hattori, Atsuhiko; Nakano, Masaki; Kakikawa, Makiko; Yamada, Sotoshi; Ogoshi, Maho; Hyodo, Susumu; Yamaguchi, Yoko; Chowdhury, Vishwajit S; Hayakawa, Kazuichi; Funahashi, Hisayuki; Sakamoto, Tatsuya; Sasayama, Yuichi

    2012-05-15

    In cartilaginous fish, two cDNAs encoding calcitonin-family receptors were isolated for the first time from the stingray brain. The open reading frame of one receptor cDNA coded a 525-amino acid protein. The amino acid identity of this receptor to human calcitonin-receptor-like receptor (CRLR) is 64.5%, frog CRLR is 64.7%, and flounder CRLR is 61.2% and this was higher than to human calcitonin receptor (CTR) (46.1%), frog CTR (54.7%), and flounder CTR (48.9%). We strongly suggested that this receptor is a ray CRLR based on phylogenetic analysis. In case of the second receptor, amino acid identity among CRLRs (human 50.5%, frog 50.7%, flounder 48.0%) and CTRs (human 43.2%, frog 49.1%, flounder 41.8%) was similar. From phylogenetic analysis of both CRLRs and CTRs, we believe that this receptor is ray CTR. The expression of ray CRLR mRNA was predominantly detected in the nervous system (brain) and vascular system (atrium, ventricle, and gill), which reflects the similar localization of CGRP in the nervous and vascular systems as mammals. It was observed that the second receptor was expressed in several tissues, namely cartilage, brain, pituitary gland, gill, atrium, ventricle, pancreas, spleen, liver, gall bladder, intestine, rectal gland, kidney, testis and ovary. This localization pattern was very similar to flounder CTR. Both receptor mRNAs were strongly expressed in the gill. This suggests that the calcitonin-family members are involved in the osmoregulation of stingray as this fish is known to be euryhaline. When a stingray was transferred to diluted seawater (20% seawater), the expression of both receptors significantly decreased in the gill. Similar results were obtained in the kidney of the stingray. Thus, our cloning and isolation of both receptors in the stingray will be helpful for elucidation of their physiological role(s) such as osmoregulation including calcium metabolism of cartilaginous fish.

  3. Calcitonin Gene-Related Peptide (Cgrp, Adrenomedullin (Am, Amylin, And Calcitonin (Ct Receptors And Overlapping Biological Actions

    Directory of Open Access Journals (Sweden)

    J.A. Fischer

    2001-01-01

    Full Text Available CGRP, AM, amylin, and CT have in common N-terminal 6-7 amino acid ring structures linked by disulfide bridges and amidated C-termini required for biological activity. For the related bioactive peptides, receptor-binding sites linked to cAMP stimulation and to a lesser extent to the phospholipase C signaling pathway have been identified in tissue specific manner. The highest density of CGRP receptors has been recognized in the cerebellum and the spinal cord. There photoaffinity-labeled N-glycosylated 60,000 and 54,000 Mr proteins are converted to 46,000 and 41,000 Mr components following endoglycosidase F/N-glycosidase F treatment. The same proteins were specifically labeled with [125I]-hCGRP-I(1-37 and -(8-37. Some cross-reaction between the CGRP receptor and AM was evident whereas amylin and CT were only recognized at over 10-7 M. A different AM receptor localized predominantly in the lung recognized CGRP at low, and amylin and calcitonin at equally high concentrations. CT receptor binding sites have been identified in osteoclasts and in the periventricular region of the brain. They cross-reacted with amylin at low concentrations and with CGRP and AM at over 10-7 M. Amylin receptor binding sites cross-reacting with salmon CT and CGRP but not with hCT and adrenomedullin to any great extent were originally described by Sexton in the nucleus accumbens and may represent a second CGRP receptor. The structure of a CT receptor was elucidated by the group of Goldring in 1991 through molecular cloning, and of a 60% homologous human CT receptor-like receptor (CRLR shortly thereafter here. The latter was an orphan receptor until the discovery of the receptor-activity-modifying proteins (RAMP by Foord which upon coexpression yield a CGRP receptor with RAMP1 and an AM receptor with RAMP2. Coexpression of the hCT receptor isotype 2 revealed a CGRP/amylin receptor with RAMP1 and an amylin receptor isotype with RAMP3. The CRLR/RAMP1 receptor antagonized by

  4. Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 9. Calcitonin in the treatment of osteoporosis.

    OpenAIRE

    Siminoski, K; Josse, R. G.

    1996-01-01

    OBJECTIVE: To describe potential therapeutic uses of calcitonin in the prevention and treatment of osteoporosis. OPTIONS: Parenterally and intranasally administered calcitonin (eel, salmon or human). OUTCOMES: Fracture, fracture pain and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures, reduction of pain and improved quality of life associated with calcitonin treatment. EVIDENCE: Relevant clinical studies and reports were examined, with an emphasis on...

  5. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis

    OpenAIRE

    Papadokostakis, G.; Damilakis, J; Mantzouranis, E.; Katonis, P.; Hadjipavlou, A.

    2005-01-01

    The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis. The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a nume...

  6. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Thomsen, Lise L; Olesen, Jes;

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine......-like attacks compared to controls. Whether CGRP triggers migraine-like attacks in FHM patients without known mutations is unknown....

  7. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    Science.gov (United States)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  8. Comparison of Calcitonin and Pamidronate Treatments in Children with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2013-08-01

    Full Text Available Purpose: The main objective of this study was to compare the treatments of calcitonin and pamidronate by clinical, biochemical, and radiological findings in children with osteogenesis imperfecta and evaluate the efficiency of pamidronate treatment. Patients and methods: A total of 12 patients, aged 41±38 (1-120 months were studied. Group 1 was consisted of six patients who had received intranasal calcitonin at a dosage of 4-6 U/kg three times a week before switching to pamidronate treatment. Group 2 was also consisted of six patients who had received only pamidronate infusion at a dosage of 0.5-2 mg/kg every two months. Results: Annual fracture rates decreased from 2.72 ± 0.80 to 0.40 ± 0.70 (p0.05, and from -3.08 ± -0.61 to -2.29 ± -0.56 in pamidronate group. The difference between the Z-scores of bone mineral density after calcitonin and pamidronate treatments was statistically significant (p<0.05. The Z-scores of pre (-3.44 ± -0.96 and post (-2.47 ± -0.60 pamidronate treatments of whole 12 patients were significantly different (p<0.001. Conclusion: Pamidronate was significantly more effective in reducing pain, annual fracture rate, and increasing bone mineral density and mobility than calcitonin without any severe adverse effects even in the neonatal period and severe forms of osteogenesis imperfecta. [Cukurova Med J 2013; 38(4.000: 667-674

  9. Physiological and clinical studies of calcium-regulating hormones calcitonin and parathyroid hormone-related protein

    OpenAIRE

    1997-01-01

    The present studies were performed to elucidate several physiological and clinical questions of calcitonin (CT) and parathyroid hormone-related protein (PTHrP) such as: a) Does age influence the basal and calcium-stimulated levels and circulating molecular forms of CT in healthy females? b) Are osteoporotic patients lacking circulating monomeric CT? c) How is salmon CT (sCT) absorbed and cleared during treatment of diseases? d) Is there any effect of acute physical activity ...

  10. The Effect of Continous or Intermittent Calcitonin in the Treatment of Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2002-03-01

    Full Text Available The aim of this study was to compare the efficacy of continuous and intermittent salmon calcitonin in the treatment of postmenopausal osteoporosis. Sixty-eight women with postmenopausal osteoporosis were randomized to 2 treatment groups. The first group consisting of 33 patients received nasal salmon calcitonin 200 IU/day. Thirty-five patients in the second group were treated with 200 IU of nasal SCT daily for 5 days with a subsequent pause of 2 days. All received a daily supplement of 1000 mg calcium. Both treatment regimen were applied for 12 months. The effect of nasal calcitonin on bone mineral density (BMDwas investigated by DEXA. Serum ALP, Ca and P levels and urinary Ca excretion were assessed before the treatment and at the end of 12 months. Serum ALP levels decreased mildly, but in a statistically significant manner in both groups ( p 0.05. There was a significant increase above baseline in the BMD of the lumbar spine, trochanteric region and Ward’s triangle in both groups (p 0.05. This study indicates that both continuous and intermittent SCT at a dosage of 200 IU/day are effective in the treatment of postmenopausal osteoporosis .

  11. A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin.

    Science.gov (United States)

    Karsdal, Morten A; Byrjalsen, Inger; Henriksen, Kim; Riis, Bente J; Christiansen, Claus

    2009-02-01

    The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 years old, randomly assigned to a comparison of dosing with ssCT (n = 12) or rsCT (n = 24) given in the morning at 08:00. Study parameters were plasma CT levels measured up to 2 hours postdose and changes in the bone resorption marker serum CTX-I and the cartilage degradation marker urine CTX-II measured up to 4 hours postdose. For both formulations, peak plasma concentrations were obtained 15 minutes after dosage, and no statistically significant differences in the uptake of CT were observed. Measurement of bone resorption and cartilage degradation markers displayed comparable responses, with AUCs of relative change of serum CTX-I of -250% x hours and relative change of urine CTX-II of -180% x hours during the 4-hour observation period. In conclusion, oral synthetic and recombinant calcitonin displayed comparable pharmacodynamic and kinetic properties.

  12. N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin.

    Science.gov (United States)

    Huang, Aiwen; Makhlof, Abdallah; Ping, Qineng; Tozuka, Yuichi; Takeuchi, Hirofumi

    2011-11-01

    Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13 ± 20.50 to 448.84 ± 103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.

  13. Calcitonin receptor gene expression in K562 chronic myelogenous leukemic cells

    Directory of Open Access Journals (Sweden)

    Pondel Marc D

    2003-04-01

    Full Text Available Abstract Background The peptide hormone calcitonin (CT can significantly effect the proliferation rate of CT receptor (CTR positive human cancer cells. We wish to identify additional human cancers expressing CTRs and assay the effects of CT on their growth rates and signal transduction pathways. Results The expression of the human calcitonin receptor (hCTR gene in the chronic myelogenous leukemia cell line K562 was examined. RT-PCR on total RNA extracted from K562 cells detected the presence of hCTR mRNA. Further analysis demonstrated that multiple hCTR isoforms were present. Incubation of K562 cells with salmon calcitonin (sCT, but not amylin, caused an increase in intracellular levels of cAMP similar to that induced by forskolin treatment. We further demonstrated that butyrate induced erythroid differentiation of K562 cells caused a significant decrease in hCTR mRNA levels. However, phorbol myristate acetate (PMA induced megakaryocytic differentiation of these cells had no significant effect on hCTR mRNA levels. We demonstrated that exposure to various concentrations of sCT had no effect on the cellular proliferation of K562 cells in vitro. Conclusion Chronic myelogenous k562 cells express multiple CTR isoforms. However, CT does not effect K562 proliferation rates. It is likely that the small increase in intracellular levels of cAMP following CT treatment is not sufficient to interfere with cellular growth.

  14. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Papadokostakis, G; Damilakis, J; Mantzouranis, E; Katonis, P; Hadjipavlou, A

    2006-03-01

    The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis. The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a numerical rating scale (NRS) and disability due to back pain was measured using the Oswestry disability questionnaire. The patients were randomly assigned to receive, for three months, either 200 IU intranasal salmon calcitonin and 1,000 mg of oral calcium daily (groups IA, IIA, IIIA) or 1,000 mg of oral calcium daily (groups IB, IIB, IIIB). Repeated measures ANOVA showed that there were no significant time, group or interaction effects for pain intensity and disability in any of the groups studied. Mean Oswestry and NRS scores were reduced during the follow-up period in the groups IA, IIIA, but the differences between the two time points were not statistically significant. Intranasal calcitonin has no effect on chronic back pain intensity and functional capacity of osteoporotic women regardless of the presence of fractures, degenerative disorders or chronic back pain of non-specific etiology.

  15. Effect of salmon calcitonin on osteoporosis and level of bone metabolism markers

    Institute of Scientific and Technical Information of China (English)

    Xian-Feng Fan; Xing-Hua Huang; Yun-Yong Huang; Ming-Jian Hu

    2015-01-01

    Objective:To study the effect of osteoporosis calcitonin salmon on the level of bone metabolism markers in patients with osteoporosis.Methods: A total of 140 cases with osteoporosis were randomly divided into control group and observation group, with 70 cases in each. Patients in control group were treated with calcitriol soft capsules and chewable calcium vitamin D. Patients in observation group were treated with salmon calcitonin.Results:The total efficiency of the observation group patients was 85.71%, significantly higher than 70.00% that of control group (P<0.05). After treatment, BMD of Torch, Neck, L1-L4 and Ward's area in observation group patients were significantly higher than that of control group (P<0.01). After treatment, bone metabolism related indicatorsβ-CTX, N-MID, ALP level in observation group patients were significantly lower than that of control group, and hCT level in observation group patients was significantly higher than that of control group (P<0.01). Conclusions:Salmon calcitonin is effective in treatment of osteoporosis. It can effectively relieve the symptoms, increase bone density and improve bone metabolism.

  16. Intrathecal Amylin and Salmon Calcitonin Affect Formalin Induced c-Fos Expression in the Spinal Cord of Rats

    Directory of Open Access Journals (Sweden)

    Zahra Khoshdel

    2014-11-01

    Full Text Available Background:Amylin and Salmon Calcitonin belong to the calcitonin family of peptides and have high affinity binding sites in the rat spinal cord. The aim of this study was to characterize receptors for Amylin and Salmon Calcitonin functionally in the spinal cord of rats. We assessed the expression of c-Fos in response to intraplantar formalin in the lumbar regions of the spinal cord in conscious rats. Methods:Amylin (0.05 nmoles or Salmon Calcitonin (0.005 nmoles was administered intrathecally (i.t. 10 minutes before the start of the formalin test. Antagonists were injected intrathecally 10 minutes before the administration of either of the peptides. Results: Two hours after formalin stimulation, rats pretreated intrathecally by either Amylin or Salmon Calcitonin, showed lower numbers of c-Fos immunoreactive nuclei in their lumbar spinal cord as compared to rats pretreated with saline. These effects were reversed upon co-administration of either of the Amylin antagonists AC187 or rat amylin8-37, but not rat α-CGRP8-37. A few cells with c-Fos immunoreactivity were found in the lumbar spinal cord of rats two hours after i.t. injection of saline, Amylin and/or Salmon Calcitonin. However, Fos-like immunoreactivity was increased in the lumbar spinal cord two hours after i.t. treatment of either of the antagonists AC187 and rat amylin8-37,when compared to saline treated rats. Conclusion:Both Amylin and Salmon Calcitonin inhibit formalin induced c-Fos expression in the rat lumbar spinal cord when administered intrathecally. Effects of the two peptides were possibly produced by undefined receptors.

  17. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Directory of Open Access Journals (Sweden)

    Stephanie White

    Full Text Available This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  18. Effects of Nasal Calcitonin vs. Oral Gabapentin on Pain and Symptoms of Lumbar Spinal Stenosis: A Clinical Trial Study.

    Science.gov (United States)

    Haddadi, Kaveh; Asadian, Leila; Isazade, Ahdie

    2016-01-01

    Lumbar spinal stenosis (LSS) is a chronic and prevalent disease that occurs in 10.8% of the general population, mostly in old age. We designed the first clinical trial study to compare the effects of administering the nasal salmon calcitonin spray and gabapentin in patients with LSS. In this clinical trial, 90 patients with symptoms of neurogenic claudication and magnetic resonance imaging-proven LSS were randomly assigned to nasal salmon calcitonin, gabapentin, or placebo treatments for eight weeks (30 participants in each group). This was followed by a washout period of four weeks. After three months of study and after four weeks off the prescription, mean values of Oswestry Disability Index in the calcitonin, gabapentin, and control groups were 23 ± 12.05, 32 ± 16.08, and 38 ± 22.09, respectively (P ≤ 0.05, calcitonin group vs. gabapentin group, and P ≤ 0. 001, calcitonin group vs. control group with respect to pretreatment scores). Thus, three months after the treatment, although most of the patients in the control group had a satisfactory period of improvement, the improvement in the calcitonin group was more than the other two groups with a significant difference (P ≤ 0.05 when compared to gabapentin group and P ≤ 0.01 when compared to placebo group). We revealed that the 200 International Unit (IU) and nasal calcitonin spray daily are more effective compared to 300 mg gabapentin three times per day and the placebo effect for eight weeks of treatment of symptoms of patients with LSS.

  19. Molecular design and prediction of bioactivity of chimeric calcitonin%嵌合降钙素的分子设计与生物学活性预测

    Institute of Scientific and Technical Information of China (English)

    王玉梅; 周一江; 张学成

    2009-01-01

    Objective:To design one new type of calcitonin(CT)analogue with higher bioactivity but lower sideeffects.Methods:According to the principle of bioactive peptide drug design and previous work experience,an assumption was raised that bioactivity of new type of calcitonin call be improved by increasing isoelectric point(pI),N-terminal hydrophobicity and C-terminal hydrophilicity of calcitonin molecules.Based on human and salmon calcitonin,a large number of calcitonin analogues were designed and then analyzed in sequence with the help of protein analysis software.The contradictions between activities and side-effects were taken into account and a new type of calcitonin analogue to meet the requirements was determined.Results:Calcitonin analogue meeting bioactivity requirements was chimeric calcitonin of human and salmon calcitonin.Structure prediction showed that the molecular conflonnation of new calcitonin analogue was similar to salmon calcitonin(sCT).The isoelectric point of chimeric calcitonin analogue was between human and salmon calcitonin.The N-terminal hydrophobicity of new calcitonin analogue Was increased more than that of human calcitonin(hCT)and as same as that of salmon calcitonin.Its C-terminal hydrophilicity was as same as that of salmon calcitonin and increased with a high degree compared with human calcitonin.Conclusion:The activity of new calcitonin analogue was predicted to have higher bioactivity than that of human calcitonin,while the side-effects was lower than that of salmon calcitonin.%目的:设计一种高活性、低副作用的降钙素类似物.方法:根据生物活件肽药物设计原理,结合前人的工作经验,提出提高降钙素分子等电点(pI)、增加N-末端疏水性和C-末端亲水性可以提高新型降钙素活件的假设.以人和鲑鱼降钙素为先导物,设计了大量的降钙素类似物,然后利用蛋白质分析计算软件,逐一分析,综合考虑到副作用与活性的矛盾,确定符合要求的新型

  20. Cellular uptake but low permeation of human calcitonin-derived cell penetrating peptides and Tat(47-57) through well-differentiated epithelial models

    DEFF Research Database (Denmark)

    Tréhin, Rachel; Krauss, Ulrike; Beck-Sickinger, Annette G;

    2004-01-01

    To investigate whether cell penetrating peptides (CPP) derived from human calcitonin (hCT) possess, in addition to cellular uptake, the capacity to deliver their cargo through epithelial barriers.......To investigate whether cell penetrating peptides (CPP) derived from human calcitonin (hCT) possess, in addition to cellular uptake, the capacity to deliver their cargo through epithelial barriers....

  1. A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats

    DEFF Research Database (Denmark)

    Andreassen, Kim V; Feigh, Michael; Hjuler, Sara T

    2014-01-01

    obese (DIO) and Zucker diabetic fatty (ZDF) rats. In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced...... a superior and pronounced reduction in food intake in conjunction with a sustained pair-fed corrected weight loss in DIO rats. Concomitantly, KBP-042 improved glucose homeostasis and reduced hyperinsulinemia and hyperleptinemia in conjunction with enhanced insulin sensitivity. In ZDF rats, KBP-042 induced......The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced...

  2. Substance P and calcitonin gene-related peptide expression in dorsal root ganglia in sciatic nerve injury rats

    Institute of Scientific and Technical Information of China (English)

    Changma Fu; Zongsheng Yin; Defu Yu; Zuhua Yang

    2013-01-01

    The neuropeptides, substance P and calcitonin gene-related peptide, have been shown to be involved in pain transmission and repair of sciatic nerve injury. A model of sciatic nerve defect was prepared by dissecting the sciatic nerve at the middle, left femur in female Sprague Dawley rats. The two ends of the nerve were encased in a silica gel tube. L5 dorsal root ganglia were harvested 7, 14 and 28 days post sciatic nerve injury for immunohistochemical staining. Results showed that substance P and cal-citonin gene-related peptide expression increased significantly in dorsal root ganglion of rats with sci-atic nerve injury. This increase peaked at 7 days, declined at 14 days, and reduced to normal levels by 28 days post injury. The findings indicate that the neuropeptides, substance P and calcitonin gene-related peptide, mainly increased in the early stages after sciatic nerve injury.

  3. Ultimobranchial gland of freshwater catfish, Heteropneustes fossilis, in response to calcitonin administration

    Directory of Open Access Journals (Sweden)

    Ajai K. Srivastav

    2009-12-01

    Full Text Available The absence o!!f a hypocalcemic effect of calcitonin (CT in fishes has been suggested due to exceedingly high plasma levels of CT; the fish may be saturated with respect of circulating CT and therefore unable to respond to exogenously administered CT. Earlier it has been suggested that a hypocalcemic action of injected CT may be obscured by changes in the release of endogenous CT and other calcium regulating hormones. In this study we have used artificial freshwater, calcium-deficient freshwater and calcium-rich freshwater and injected the fish with CT. The aim behind selecting these media were (i in calcium-deficient medium there would be reduced circulating levels of CT, (ii in calcium-rich medium there would be diminished secretion of prolactin (this hormone is hypercalcemic in fish, and (iii by keeping the fish in calcium-rich medium we can test the antihypercalcemic action of CT. Moreover, the present study would reveal the changes in the ultimobranchial gland (UBG after keeping the fish in all the above three media and/or injecting the fish with CT. Freshwater catfish, Heteropneustes fossilis, were administered intraperitoneally daily with vehicle or 0.5 U/100g body wt of salmon calcitonin (CT and kept in artificial freshwater, calcium-rich freshwater and calcium-deficient freshwater for 10 days. Blood samples were collected on 1, 3, 5, and 10 days following the treatment and analyzed for serum calcium levels. The ultimobranchial gland (UBG was also fixed for histological studies on these intervals. In artificial freshwater there was no change in the serum calcium levels of calcitonin-injected fish. The ultimobranchial gland of calcitonin-injected fish exhibited a progressive decrease in the nuclear volume from day 5 onwards. On day 10 vacuolization in the gland was also noticed. In vehicle-injected fish (control kept in calcium-rich freshwater hypercalcemia has been noticed which persists till the end of the experiment. In calcitonin

  4. The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic patients with back pain.

    Science.gov (United States)

    Ofluoglu, D; Akyuz, G; Unay, O; Kayhan, O

    2007-01-01

    The purpose of this study was to evaluate the efficacy of calcitonin on beta-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis. The secondary purpose was to assess the pain and quality of life in these patients. There were 30 patients with a mean age of 58.2+/-5.4 years in the treatment group and 26 patients with a mean age of 58.8+/-5.2 years in the placebo group in this randomized, placebo-controlled study. The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks. Baseline plasma beta-endorphin levels were measured and repeated after 2 weeks. Patients' pain and quality of life (QOL) were evaluated by using the Visual Analogue Scale, Modified Face Scale, Beck Depression Index, and Nottingham Health Profile. Patients' global assessment of disease activity was also performed at baseline and at the end of the first and second week. We found that plasma beta-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week (p<0.001). Although pain and QOL scores were improved at the end of the second week in both groups (p<0.05), the improvement in the treatment group was more significant when compared with the placebo group (p<0.05). Therefore, calcitonin is an analgesic agent, as it increases the plasma beta-endorphin levels in patients with postmenopausal osteoporosis, which consequently improves QOL.

  5. The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H.; Johnson, Kirk W.

    2017-01-01

    Abstract Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine. PMID:28301400

  6. Treatment of aneurysmal bone cysts by percutaneous CT-guided injection of calcitonin and steroid

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Connie Y.; Kattapuram, Susan V.; Huang, Ambrose J.; Simeone, F.J.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital, Department of Radiology Division of Musculoskeletal Imaging and Intervention, Boston, MA (United States)

    2017-01-15

    To determine the efficacy and safety of percutaneous calcitonin and steroid injection in the treatment of aneurysmal bone cysts (ABCs). Our study was IRB-approved and HIPAA-compliant. We reviewed pre- and post-procedural imaging studies and medical records of all CT-guided percutaneous injections of ABCs with calcitonin and steroid performed at our institution between 2003 and 2015. Treatment success based on imaging was categorized as substantial (51-100 %), partial (1-50 %), or none (0 %) by comparing radiographs of the lesion before and after treatment. Our study group comprised 9 patients (7 female, 2 male; mean age 19 ± 5 (range 12-25) years). ABCs were located in the pubis (n = 3), femur (n = 2), and humerus/scapula/ilium/sacrum (n = 1 for each). One patient did not have any clinical or imaging follow-up. For the other 8 patients, clinical and imaging follow-up ranged from 1 to 93 months (mean 16 ± 29 months). One patient had two injections, and 1 patient had three injections. Six out of eight patients (75 %) had complete symptomatic relief and 2 patients (25 %) had partial symptomatic relief after initial injection. Imaging follow-up revealed substantial imaging response in 4 out of 8 patients (50 %). There was a partial imaging response in 2 patients (25 %) and no imaging response in 2 out of 8 patients (25 %), and all 4 of these patients had local recurrence. There were no complications. Percutaneous CT-guided injection of ABCs with calcitonin and steroid is a safe and effective treatment. Lack of imaging response may necessitate more aggressive treatment to minimize local recurrence. (orig.)

  7. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine.

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H; Johnson, Kirk W

    2017-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene-related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene-related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

  8. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are i...... releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels.......Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons...

  9. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Hauge, Anne Werner; Olesen, J.

    2010-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did...... not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls....

  10. Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and challenges in treating headache.

    Science.gov (United States)

    Peroutka, Stephen J

    2014-06-01

    A role for calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine has been established over the past 25 years. There have now been at least five different small-molecule CGRP antagonists that have demonstrated statistical proof of efficacy in the acute treatment of migraine. At present, multiple clinical trials are underway that are assessing the ability of long-acting antibodies against CGRP to prevent frequent migraine attacks. This review summarizes the existing data concerning the role of CGRP in migraine and attempts to highlight some possible outcomes from the ongoing anti-CGRP antibody trials.

  11. Salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis.

    Science.gov (United States)

    Dexue, Liu; Yueyue, Zheng

    2014-11-01

    To explore the reasonable treatment scheme of salmon calciteonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis, patients were randomly divided into Group A, B and C, and they were given the salmon calcitonin every time 50 IU, subcutaneous injection. The Group A were 1 time a day, for 15 days; Group B were 1 time every 2 days, for 30 days; Group C, one time three days for 90 days. Then to observe the symptoms have efficiency, bone density T value change, incidence rate, incidence of side effects and treatment of loss rate of fracture. Efficiency of symptoms: Group A is lower and there is no difference in Group B and C. T Degree: Group C was significantly increased and Group A was the lowest. Fracture incidence of Group B and C were significantly lower than Group A, and there is no difference in Group B and C. Turnover rate: Group A was significantly lower than B and C, and there is no difference in Group B and C. There is low incidence of side effects in the three groups and they three have no significant difference. It is effective and safe to use salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis. 50 IU each time, subcutaneous injection, 1 time every 3 days, for 3 months is a reasonable solution.

  12. Long-term treatment of osteogenesis imperfects tarda in adults with salmon calcitonin and calcium

    Energy Technology Data Exchange (ETDEWEB)

    Zanzi, I.; Wallach, S.; Ellis, K.J.; Aloia, J.F.; Atkins, H.L.; Cohn, S.H.

    1976-02-01

    Three postmenopausal women with osteogenesis imperfecta (O.I.) tarda were treated with daily salmon calcitonin (sCT) and calcium supplements for 12 to 33 months. Total body calcium (TBCa) measured by total body neutron activation analysis revealed a marked deficit exceeding that of severely osteoporotic women. In one patient a rapid loss of TBCa of 5 percent at five months of treatment was partially reversed after twelve months of treatment. In eight subsequent months of Ca supplementation alone, the loss of TBCa resumed and amounted to 11 percent. The second patient increased TBCa by 9 percent after a total of 33 months of sCT and Ca supplementation. The third patient also showed a rapid decrease in TBCa of 8 percent during one year of sCT and Ca, but she was also receiving systemic corticosteroids for asthma. Her TBCa recovered to 8 percent above baseline eight months after stopping sCT, continuation of the Ca and a drastic decrease in the dose of corticosteroids. The action of sCT in this patient might have been impaired by the concomitant administration of corticosteroids. Urinary hydroxyproline decreased from initial normal values in two patients suggesting continued inhibition of bone resorption. The results confirm previous work using calcitonin in children with O.I. and suggest that sCT may also be of benefit in adults with O.I. (auth)

  13. A specific Tween-80-Rhodamine S-MWNTs phosphorescent reagent for the detection of trace calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Liu Jiaming, E-mail: zzsyliujiaming@163.com [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Zhangzhou, 363000 (China); Huang Xiaomei; Zhang Lihong; Zheng Zhiyong [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Zhangzhou, 363000 (China); Department of Food and Biological Engineering, Zhangzhou Institute of Technology, Zhangzhou, 363000 (China); Lin Xuan; Zhang Xiaoyang; Jiao Li; Cui Malin [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Zhangzhou, 363000 (China); Jiang Shulian [Fujian Provincial Bureau of Quality and Technical Supervision, Zhangzhou, 363000 (China); Lin Shaoqin [Department of Biochemistry, Fujian Education College, Fuzhou 350001 (China)

    2012-09-26

    Graphical abstract: A new Tween-80-Rhodamine S-water-soluble multi-walled carbon nanotubes (Tween-80-Rhod.S-MWNTs-EDC-NHS, TRMEN) phosphorescent labelling reagent was developed. High sensitive solid substrate room temperature phosphorescence immunoassay (SSRTPIA) for the determination of calcitonin (CT) in human serum and the prediction of human diseases based on the TRMEN could be used to label anti-calcitonin antibody (Ab{sub CT}) to form the TRMEN-Ab{sub CT} labelling product, which could take high specific immunoreaction with CT causing that the {Delta}I{sub p} of the system was linear to the content of CT. Moreover, the reaction mechanisms of both labelling Ab{sub CT} by TRMEN and SSRTPIA for the determination of trace CT were discussed. This research not only provides a new hormones analysis method, but also expands the application field of MWNTs and promotes the development of SSRTP and IA. --Highlights: Black-Right-Pointing-Pointer A Tween-80-Rhodamine S-multi-walled carbon nanotubes labelling reagent was developed. Black-Right-Pointing-Pointer The phosphorescence immunoassay was established for the determination of calcitonin. Black-Right-Pointing-Pointer This method has been applied to determine CT and the prediction of diseases. Black-Right-Pointing-Pointer The structure of MWNTs was characterized with SEM and IR. Black-Right-Pointing-Pointer The mechanisms for both determining trace CT and labelling Ab{sub CT} were discussed. - Abstract: The present study proposed a simple sensitive and specific immunoassay for the quantification of calcitonin (CT) in human serum with water-soluble multi-walled carbon nanotubes (MWNTs). The -COOH group of MWNTs could react with the -NH- group of rhodamine S (Rhod.S) molecules to form Rhod.S-MWNTs, which could emit room temperature phosphorescence (RTP) on acetate cellulose membrane (ACM) and react with Tween-80 to form micellar compound. Tween-80-Rhod.S-MWNTs (TRM), as a phosphorescent labelling reagent, could

  14. Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study.

    Science.gov (United States)

    Lyritis, G P; Tsakalakos, N; Magiasis, B; Karachalios, T; Yiatzides, A; Tsekoura, M

    1991-12-01

    Back pain due to vertebral collapse is the main symptom of postmenopausal osteoporosis. The clinical picture in these crush fractures varies, depending on the type and the location of fracture, but in general, a new vertebral crush fracture gives rise to severe pain that immobilizes the patient and necessitates bedrest. In this double-blind controlled clinical trial, 56 patients who had recently (within the last 3 days) suffered an osteoporotic vertebral fracture were hospitalized for a period of 14 days. Salmon calcitonin (100 IU) or placebo injections were given daily. Pain was rated daily on a 10-point scale by the same observers. Blood and urinary parameters were also evaluated. The results showed a significant (P less than 0.001) difference in pain intensity between the calcitonin group and the placebo group. This beneficial effect was generally apparent from the second day of treatment onward, and over the following 2 weeks, the patients were able to sit and stand, and gradually started to walk again. A significant decrease in urinary hydroxyproline and urinary calcium was also noted in the calcitonin group. It is concluded that calcitonin exerts a beneficial effect on back pain following a vertebral crush fracture.

  15. Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

    NARCIS (Netherlands)

    Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

    2006-01-01

    The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium nitroprus

  16. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers

    DEFF Research Database (Denmark)

    Kruuse, C; Iversen, Helle Klingenberg; Jansen-Olesen, I

    2010-01-01

    calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers...

  17. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J;

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are i...

  18. Parathyroid hormone, calcitonin, and vitamin D 1974: Present status of physiological studies and analysis of calcium homeostasis

    Science.gov (United States)

    Potts, J. T., Jr.; Swenson, K. G.

    1975-01-01

    The role of parathyroid hormone, calcitonin, and vitamin D in the control of calcium and bone metabolism was studied. Particular emphasis was placed on the physiological adaptation to weightlessness and, as a potential model for this purpose, on the immobilization characteristic of space flight or prolonged bed rest. The biosynthesis, control of secretion, and metabolism of these hormonal agents is considered.

  19. Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat

    DEFF Research Database (Denmark)

    Bergdahl, A; Valdemarsson, S; Nilsson, T;

    1999-01-01

    It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status...

  20. A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats

    DEFF Research Database (Denmark)

    Feigh, M; Henriksen, K; Andreassen, K V

    2011-01-01

    To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes....

  1. The effects of fasting and refeeding on serum parathormone and calcitonin concentrations in young and old male rats.

    Science.gov (United States)

    Kmieć, Z; Myśliwski, A; Wyrzykowska, M; Hoppe, A

    2001-05-01

    Although fasting and refeeding reveal the existence of age-related changes in carbohydrate and lipid metabolism, the effects of aging on mineral metabolism in refed animals are unknown. We therefore investigated hormonal regulation of calcium metabolism in young (4 months) and old (26 months) male rats fasted for 48 hours and then refed for 4 or 24 hours. Serum concentrations of total and ionized calcium and parathormone were similar in control young and old rats. Serum calcitonin level was higher, and the concentrations of albumin and inorganic phosphate and alkaline phosphatase activity were lower in fed old rats. In young fasted rats, the serum ionized and total calcium was decreased, and phosphate concentration was increased. In old rats, fasting resulted in the increase of serum parathormone level. Fasting reduced serum alkaline phosphatase activity to a similar extent in both age groups. In young rats, refeeding for 24h normalized serum calcium and phosphate levels and alkaline phosphatase activity, and decreased serum concentrations of PTH and calcitonin. In old refed rats, serum calcitonin concentration was raised by 77% compared to fed or fasted animals, whereas parathormone levels were normalized. Our results indicate that old fasted or refed rats maintain normal serum calcium concentration in a different way than young animals, possibly through the increase in serum levels of parathormone and/or calcitonin. Thus, dietary manipulations such as fasting and refeeding constitute an interesting model for the investigation of the effects of aging on the hormonal regulation of serum calcium level.

  2. Spinal-cord syndrome due to non-compressive Paget's disease of bone: a spinal-artery steal phenomenon reversible with calcitonin.

    Science.gov (United States)

    Herzberg, L; Bayliss, E

    1980-07-05

    A 76-year-old man had progressive low back pain, leg weakness, and sensory loss. Radiology showed changes consistent with wide-spread Paget's disease, but no cord compression or involvement of nerve roots was detected by myelography or computerised axial tomography. His symptoms were relieved within 12 days of starting 100 MRC units of subcutaneous salmon calcitonin and recurred when calcitonin was discontinued for 5 days. The improvement continued on calcitonin treatment for 1 year, with falls in serum alkaline phosphatase and urinary hydroxyproline excretion. It is suggested that calcitonin treatment, in reducing the abnormally high metabolic activity of the diseased bone, and hence its vascular perfusion, allows more blood to reach the spinal cord.

  3. Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia

    NARCIS (Netherlands)

    H. IJsselstijn (Hanneke); N. Hung; J.C. de Jongste (Johan); D. Tibboel (Dick); E. Cutz

    1998-01-01

    textabstractCongenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previo

  4. Two-dimensional NMR and structure determination of salmon calcitonin in methanol

    Energy Technology Data Exchange (ETDEWEB)

    Meadows, R.P.; Nikonowicz, E.P.; Jones, C.R.; Gorenstein, D.G. (Purdue Univ., Lafayette, IN (USA)); Bastian, J.W.

    1991-02-05

    The structure of the 32-residue peptide salmon calcitonin (sCT) in 90% MeOH-10% H{sub 2}O has been investigated by two-dimensional NMR techniques and molecular modeling. Sequential assignments for nearly all of the 32 spin systems have been obtained, and results indicate that the heptaresidue loop formed by the disulfide bond between Cys-1 and Cys-7 is followed by an {alpha}-helical segment from Val-8 through Tyr-22. A region of conformational heterogeneity is observed for residues 20-25, resulting from the slow isomerism of the cis and trans forms of Pro-23. The C-terminal segment is found to exist in an extended conformation.

  5. Measurement of total body calcium in osteoporotic patients treated with salmon calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Zanzi, I.; Thompson, K.; Cohn, S.H.

    1981-01-01

    In the past, the evaluation of therapies for osteoporosis has been limited by the lack of a suitable quantitative end point. The introduction of the technique of in vivo total body neutron activation analysis (TBNAA) has made possible the precise and accurate measurement of total body calcium (TBCa). Since almost 99 percent of TBCa is in the skeleton, TBNAA gives a direct measurement of skeletal mass. Thus, changes in skeletal mass serve as an objective criterion in the evaluation of the efficacy of the therapy in osteoporosis. Studies performed at Brookhaven National Laboratory and elsewhere have reported the use of calcitonin (CT) in the treatment of primary osteoporosis and related conditions in a limited number of patients. The physiological effects of CT as an inhibitor of bone resorption has been the rationale of its use. The results of a randomized, controlled, 2 year therapeutical trial of CT in a group of postmenopausal osteoporotic women are presented in this report.

  6. Calcitonin receptors in the rat mesencephalon mediate its analgesic actions: autoradiographic and behavioral analyses

    Energy Technology Data Exchange (ETDEWEB)

    Fabbri, A.; Pert, C.B.; Pert, A.; Fraioli, F.

    1985-09-23

    Autoradiographic analyses of salmon calcitonin (sCT) binding in the rat mesencephalon revealed an exceptionally high concentration of receptors in the ventral and ventrolateral segments of the periaqueductal gray matter (PAG) extending along the entire rostralcaudal axis. Relatively heavy labeling was also seen along a band extending ventrolaterally through the mesencephalic reticular formation. Other receptor-rich areas include the nucleus linearis, pars compacta and lateralis of the substantia nigra, locus coeruleus, parabrachial nuclei and nucleus raphe pontis of the pontine reticular formation. The biological effects are consistent with the potencies of both peptides in displacing SVI-sCT from slide-mounted sections of rat PAG. Naloxone failed to antagonize sCT-induced analgesia, suggesting an opiate independent mechanism for this peptide in elicting analgesia. (Auth.). 60 refs.; 9 figs.

  7. Calcitonin gene-related peptide does not cause the familial hemiplegic migraine phenotype

    DEFF Research Database (Denmark)

    Hansen, J.M.; Thomsen, L.L.; Olesen, J.

    2008-01-01

    Objective: The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine...... without aura. This indicates that the pathophysiologic pathways underlying migraine headache in FHM may be different from the common types of migraine and questions whether CGRP antagonists would be effective in the treatment of FHM patients Udgivelsesdato: 2008/9/9...... with aura associated with several gene mutations. FHM shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. We tested the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype. Methods: We included 9 FHM patients with known...

  8. The Comparison of Effects of Alendronate and Calcitonin Treatment in Men With Osteoporosis

    Directory of Open Access Journals (Sweden)

    Gülcan Gürer

    2004-09-01

    Full Text Available In recent years, there has been a dramatic increase in research investigating the epidemiology, diagnosis, prevention, and treatment of osteoporosis and fragility fractures in men. This study was performed to compare the effects of alendronate and calcitonin treatment in male OP osteoporosis. Thirty men with osteoporosis were enrolled in this study. Bone mineral density (BMD was measured at the proximal femur and lumbar spine by using dual-photon absorptiometry. Thirty men with osteoporosis were randomly divided into two groups. BMD was measured twice as before the treatment and one year later. The end of the treatment a significant improvement was found in the BMD levels of the lomber spine in both groups (p0.05. There was no significant difference of BMD levels of proximal femur when the results were compared either within the groups or between two groups (p>0.05.

  9. Pentagastrin, calcium and whisky stimulated serum calcitonin in medullary carcinoma of the thyroid.

    Science.gov (United States)

    Emmertsen, K K; Nielsen, H E; Mosekilde, L; Hansen, H H

    1980-01-01

    The efficiency of pentagastrin, calcium and whisky in raising serum immunoreactive calcitonin (S-iCT) concentrations was analysed in 6 patients with medullary carcinoma of the thyroid and in 8 healthy controls. All 6 patients responded to pentagastrin with a significant increase in S-iCT, 5 responded to calcium and only 3 to whisky. In the 8 controls no or only a modest increase in S-iCT occurred following pentagastrin, calcium and whisky with no difference between the three. It is concluded that pentagastrin is the most useful stimulative agent for ICT secretion in patients with C-cell neoplasms. In selected cases the additional use of calcium could be advantageous.

  10. Crystal Structure of the DFNKF Segment of Human Calcitonin Unveils Aromatic Interactions between Phenylalanines.

    Science.gov (United States)

    Bertolani, Arianna; Pizzi, Andrea; Pirrie, Lisa; Gazzera, Lara; Morra, Giulia; Meli, Massimiliano; Colombo, Giorgio; Genoni, Alessandro; Cavallo, Gabriella; Terraneo, Giancarlo; Metrangolo, Pierangelo

    2017-02-10

    Although intensively studied, the high-resolution crystal structure of the peptide DFNKF, the core-segment of human calcitonin, has never been described. Here we report how the use of iodination as a strategy to promote crystallisation and facilitate phase determination, allowed us to solve, for the first time, the single-crystal X-ray structure of a DFNKF derivative. Computational studies suggest that both the iodinated and the wild-type peptides populate very similar conformations. Furthermore, the conformer found in the solid-state structure is one of the most populated in solution, making the crystal structure a reliable model for the peptide in solution. The crystal structure of DFNKF(I) confirms the overall features of the amyloid cross-β spine and highlights how aromatic-aromatic interactions are important structural factors in the self-assembly of this peptide. A detailed analysis of such interactions is reported.

  11. Calcitonin gene-related peptide (CGRP) in the nipple of the rat mammary gland

    DEFF Research Database (Denmark)

    Thulesen, J; Rasmussen, T N; Schmidt, P;

    1994-01-01

    The distribution of nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) was investigated by immunohistochemistry in nipples and mammary glands from lactating and non-lactating rats and compared to the immunoreactivity of other neuropeptides including substance P (SP), neuropeptide...... Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM). The study revealed an extensive innervation of the mammary nipples, in which CGRP-immunoreactive (IR) nerve fibres were abundantly present in the epidermis, dermal connective tissue and intralobular connective tissue of the mammary...... gland parenchyma. Several of the dermal CGRP-IR fibres seemed to follow blood vessels, or formed "ringlet-like" structures. The latter were mostly observed in the dermal connective tissue of the nipple from the lactating rat and may have a mechanoreceptive function, e.g. for the suckling stimuli...

  12. CALCITONIN GENE-RELATED PEPTIDE INDUCES FIBROBLASTS FROM HIP PSEUDOCAPSULE TO PRODUCE CYTOKINES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate calcitonin gene-related peptide (CGRP) involvement in the process of aseptic loosening. Methods We isolated fibroblasts from periprosthetic pseudocapsular tissue at the time of revision hip arthroplasty performed due to aseptic loosening. Fibroblasts were incubated for 24 h in the presence of CGRP, and the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the media were determined using enzyme-linked immunosorbent assay kit. Results We found that the levels of IL-1β, IL-6, and TNF-α increased in a time- and concentration-dependent manner. ConclusionThese inflammatory cytokines play an important role in the development of periprosthetic osteolysis and implant loosening. Our results suggest that CGRP may be involved in the pathogenesis of aseptic loosening.

  13. A sup 1 H NMR study of human calcitonin in solution

    Energy Technology Data Exchange (ETDEWEB)

    Motta, A. (Consiglio Nazionale delle Richerche, Napoli (Italy)); Temussi, P.A. (Univ. di Napoli (Italy)); Wuensch, E.; Bovermann, G. (Max-Planck-Inst. fuer Biochemie, Martinsried bei Muenchen (West Germany))

    1991-03-05

    Human calcitonin (hCT) has been investigated by NMR at 400 MHz in DMSO{sub d6} and in an 85% DMSO{sub d6}-15% {sup 1}H{sub 2}O (v/v) cryoprotective mixture. All backbone and side-chain resonances have been assigned and the secondary structure has been determined in both solvents. In DMSO{sub d6}, the simultaneous presence of d{sub {alpha}N}, d{sub NN}, and some specific weak medium-range nuclear Overhauser effects, together with the amide temperature coefficients and the analysis of the NH-{alpha}CH spin-spin coupling constants, indicates that hCT is highly flexible but with three domains (comprising segments Asn{sup 3}-Gly{sup 10}, Gln{sup 14}-Thr{sup 21}, and Thr{sup 25}-Ala{sup 31}) in extended conformations which dynamically transform into isolated {beta} turns in the N- and C-terminal regions and into adjacent tight turns, resembling a 3{sub 10} helix structure, in the central part. The DMSO-water mixture rigidifies the polypeptide chain, favoring and ordered, extended conformation. NOESY data indicate the presence of a short double-stranded antiparallel {beta} sheet in the central region made by residues 16-21 and connected by a two-residue hairpin loop formed by residues 18 and 19. Two tight turns, formed by residues 3-6 and 28-31, were also identified. The central {beta} sheet does not favor an amphipathic distribution of the residues as found for salmon calcitonin. This is in agreement with the smaller tendency of hCT to form the amphipathic {alpha} helix, postulated to be responsible for the interaction of hCT with lipids. The possible role of the cis-trans isomerism of Pro is discussed.

  14. Metal ions as cofactors for aggregation of therapeutic peptide salmon calcitonin.

    Science.gov (United States)

    Rastogi, Neeraj; Mitra, Kalyan; Kumar, Dinesh; Roy, Raja

    2012-05-21

    The effects of multivalent metal ions (Cu(2+)/Zn(2+)/Al(3+)) on the aggregation of salmon calcitonin (sCT)--a therapeutic peptide used worldwide in the treatment of osteoporosis and Paget's disease--have been studied in vitro using NMR (both solution state and solid state), TEM, ThT-fluorescence, and FT-IR spectroscopy. Overall, the various results indicated that the metal-ions-induced conformational transitions in the peptide--mostly toward the β-sheet--facilitate the aggregation of sCT in solution. First, the solution NMR has been used to check the interaction between the peptide and the metal ions. Following this, the formation and characterization of calcitonin aggregates has been performed using TEM, solid state NMR, and FT-IR spectroscopy. The TEM and ThT-fluorescence results revealed that the sCT peptide incubated with Cu(2+) and Zn(2+) metal ions (in aqueous environment) forms globular aggregates, while that with Al(3+) ions forms fibrils. The solid state NMR and FT-IR studies revealed the presence of a substantial amount of β-sheet content in sCT aggregates (formed in the presence of these metal ions) compared to the monomeric sCT, indicating that the metal binding is concomitant with conformational changes. The present study becomes crucial while prescribing this drug peptide under physio-pathological conditions associated with an abnormal accumulation of metal ions (Cu(2+)/Zn(2+)/Al(3+)) in the body (i.e., abnormal metal ion homeostasis).

  15. Application of the yeast-surface-display system for orally administered salmon calcitonin and safety assessment.

    Science.gov (United States)

    Sun, Ping-Nan; Zhang, Xue-Cheng; Chen, Yun-Song; Zang, Xiao-Nan

    2010-01-01

    High manufacturing costs and oral delivery are the constraints in clinical application of calcitonin. We selected surface-displayed Saccharomyces cerevisiae as a low-cost and safe carrier for oral delivery of salmon calcitonin (sCT). The sCT DNA fragment, optimized according to the codon preference of S. cerevisiae, was synthesized and cloned into the plasmid M-pYD1 to yield recombinant yAGA2-sCT, which was induced to express sCT by galactose for 0, 12, and 24 h. sCT expression was detected on the cell surface by indirect immunofluorescence and peaked at 12 h. About 65% recombinants expressed sCT on flow cytometry. The in vivo and in vitro activity of recombinant sCT was determined by detecting bioactivity of antiosteoclastic absorption on bone wafers and orally administering yAGA2-sCT to Wistar rats, respectively. For safety assessment of yAGA2-sCT, we observed abnormalities, morbidity, and mortality and determined body weight, serum chemistry parameters, hematological parameters, and organ weight. In vitro bioactivity of the recombinant sCT was similar to that of commercial sCT, Miacalcic; oral administration of 5 g/kg yAGA2-sCT induced a long-term hypocalcemic effect in Wistar rats and no adverse effects. This study demonstrates that yAGA2-sCT anchoring sCT protein on a S. cerevisiae surface has potential for low-cost and safe oral delivery of sCT.

  16. Preliminary study on androgen dependence of calcitonin gene-related peptide in rat penis

    Institute of Scientific and Technical Information of China (English)

    Zhou-Jun Shen; Shan-Wen Chen; Ying-Li Lu; Liao-Yuan Li; Xie-Lai Zhou; Ming-Guang Zhang; Zhao-Dian Chen

    2005-01-01

    Aim: To study the androgen dependence of the neurotransmitter, calcitonin gene-related peptide (CGRP) in rat penis.Methods: Forty-four Sprague-Dawley rats were randomly divided into Group A (intact controls), Group B (castrated)group were anaesthetized. Blood samples were taken for the measurement of serum testosterone and dihydrotestosterone (DHT) by means of radioimmunoassay. Penile samples were harvested for the investigation of calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers with immunohistochemistry. The computer-assisted imaging analysis system was applied to calculate the area proportion of the CGRP-positive nerve fibers (CGRP-PNF) in each group.Results: 1) Both 4 and 10 weeks later, testosterone and DHT levels in Group B decreased significantly compared with those in Group A, (P<0.05, P<0.01, respectively); DHT level in Group C was also significantly decreased in comparison with that in Group A for both 4- and 10- week animals (P < 0.05); 2) There was no significant differences in area proportion of CGRP-PNF among Groups A, B and C 4 weeks after treatments (P > 0.05); However, 10weeks later, the proportion of CGRP-PNF in Groups B and C was significantly less than that in Group A (P < 0.01);3) The proportion of CGRP-PNF of 4-week animals in Groups B and C was significantly higher than that of 10-week animals (P<0.05). Conclusion: The expression of neurotransmitter, CGRP may depend on androgens, including testosterone and DHT in rat penis.

  17. Insights into interactions between the alpha-helical region of the salmon calcitonin antagonists and the human calcitonin receptor using photoaffinity labeling.

    Science.gov (United States)

    Pham, Vi; Dong, Maoqing; Wade, John D; Miller, Laurence J; Morton, Craig J; Ng, Hooi-Ling; Parker, Michael W; Sexton, Patrick M

    2005-08-05

    Fish-like calcitonins (CTs), such as salmon CT (sCT), are widely used clinically in the treatment of bone-related disorders; however, the molecular basis for CT binding to its receptor, a class II G protein-coupled receptor, is not well defined. In this study we have used photoaffinity labeling to identify proximity sites between CT and its receptor. Two analogues of the antagonist sCT(8-32) containing a single photolabile p-benzoyl-l-phenylalanine (Bpa) residue in position 8 or 19 were used. Both analogues retained high affinity for the CT receptor and potently inhibited agonist-induced cAMP production. The [Bpa(19)]sCT(8-32) analogue cross-linked to the receptor at or near the equivalent cross-linking site of the full-length peptide, within the fragment Cys(134)-Lys(141) (within the amino terminus of the receptor, adjacent to transmembrane 1) (Pham, V., Wade, J. D., Purdue, B. W., and Sexton, P. M. (2004) J. Biol. Chem. 279, 6720-6729). In contrast, proteolytic mapping and mutational analysis identified Met(49) as the cross-linking site for [Bpa(8)]sCT(8-32). This site differed from the previously identified cross-linking site of the agonist [Bpa(8)]human CT (Dong, M., Pinon, D. I., Cox, R. F., and Miller, L. J. (2004) J. Biol. Chem. 279, 31177-31182) and may provide evidence for conformational differences between interaction with active and inactive state receptors. Molecular modeling suggests that the difference in cross-linking between the two Bpa(8) analogues can be accounted for by a relatively small change in peptide orientation. The model was also consistent with cooperative interaction between the receptor amino terminus and the receptor core.

  18. Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B W

    2016-01-01

    BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we record...... cortex. Sumatriptan injection reversed these changes. CONCLUSION: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.......BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...

  19. The Effect of Alendronate and Calcitonin Treatments on Bone Mineral Density and Quality of Life in Women With Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2002-06-01

    Full Text Available The aim of this study was to compare the effect of alendronate and calcitonin treatments on bone mineral density (BMD and quality of life of women with postmenopausal osteoporosis. One hundred ninety-three patients were randomly assigned to two groups: 93 patients received daily doses of 10 mg alendronate and calcium 1000 mg, and 98 patients used intranasal salmon calcitonin (sCt at a dosage of 200 IU/day and they also received daily doses of 1000 mg calcium supplements. DXA was used for the measurement of BMD of the lumbar spine and proximal femur before and after the study period. SF-36 was used as a measure of health-related quality of life. At the end of the treatment, ALN produced significant increases in BMD at the lumbar spine (p< 0.001, femur neck (p<0.05, trochanteric region (p<0.001 and at the Ward triangle (p<0.05. In contrast, intranasal sCt treatment resulted in a significant bone loss in the femur neck (p<0.01 and Ward triangle (p<0.05, and only a significant increase in BMD of the lumbar spine was observed with calcitonin treatment(p< 0.05. Quality of life as assessed by SF-36 improved significantly in both groups(p<0.05. In conclusion, alendronate seemed to be more effective than calcitonin, increasing both spinal and femoral BMD, for the treatment of postmenopausal osteoporosis. Both treatments were found to be effective for the improvement of quality of life.

  20. Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat

    OpenAIRE

    Liu, Chang-Cheng; Tian, Fa-Ming; Zhou, Zhuang; Wang, Peng; Gou, Yu; Zhang, Heng; Wang, Wen-Ya; Shen, Yong; Zhang, Ying-Ze; Zhang, Liu

    2015-01-01

    Background Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneratio...

  1. RELATIONSHIP BETWEEN THE PATTERN OF METHYLATION OF CALCITONIN GENE AND ACTIVITY OF METHYLTRANSFERASE in 8 Tumor Cell Lines

    Institute of Scientific and Technical Information of China (English)

    BAI; Zhi-yong

    2001-01-01

    [1]Baylin SB, Fearon ER, Vogeletein B, et al. Hyper- methylation of 5' the region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies [J]. Blood 1987; 70:412.[2]Nelkin BD, Przepiorka D, Burke PJ, et al. Abnormal methylation of the calcitonin gene marks progression of chronic myelogenous leukemia [J]. Blood 1991; 77: 2431.[3]Ritter M, Kant EDe, Huhn D, et al. Detection of DNA methylation in the calcitonin gene in human leukemias using differential polymerase chain reaction [J]. Leukemia 1995; 9:915.[4]Wu SL, Xie GL, Bai RK, et al. Semi-quantitative study of calcitonin gene methylation in myelodysplastic syndrome [J]. Chin Med J 1998; 111:690.[5]Admas RL, Rinaldi A, Seivwright CA. Microassay for DNA methyltranferase [J]. J Biochem Biophys Methods 1991; 22:19.[6]Bai ZY, Xu GB, Wu SL. Detection of DNA- methyl- tranferase activity of leukemia cells with radiology microassay [J]. J Beijing Med Univ 2000; 32:76.[7]Issa J, Veritino PM, Wu J, et al. Increased cytosine DNA- Methyltranferase activity during colon cancer pro- gression [J]. J Natl Cancer Inst 1993; 85:1235.[8]Vertino PM, Yen RW, Gao J, et al. De novo methylation of CpG islands sequences in human fibroblasts overexpression DNA (cytosine-5-) methyltranferase [J]. Mol cell Bio 1996; 16:4555.[9]Robertson KD, Uzvolgyi E, Liang G, et al. The human DNA methyltranferase (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissue and overexpression in tumors [J]. Nucleic Acids Res 1999; 27:2291.[10]Okano M, Bell DW, Haber DA, et al. DNA methyl- tranferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development [J]. Cell 1999; 99:247.

  2. Development of Calcitonin Salmon Nasal Spray: similarity of peptide formulated in chlorobutanol compared to benzalkonium chloride as preservative.

    Science.gov (United States)

    Costantino, Henry R; Culley, Heather; Chen, Lishan; Morris, Daniel; Houston, Michael; Roth, Sharin; Phoenix, Mary Jo; Foerder, Chuck; Philo, John S; Arakawa, Tsutomu; Eidenschink, Lisa; Andersen, Niels H; Brandt, Gordon; Quay, Steven C

    2009-10-01

    The similarity of an intranasal salmon calcitonin (sCT) employing chlorobutanol as preservative (Calcitonin Salmon Nasal Spray) was compared to the reference listed drug (RLD) employing benzalkonium chloride as preservative (Miacalcin Nasal Spray). Various orthogonal methods assessed peptide structuring, dynamics, and aggregation state. Mass spectrometry, amino acid analysis, and N-terminal sequencing all demonstrated similarity in primary structure. Near- and far-UV circular dichroism (CD) data supported similarity in secondary and tertiary sCT structure. Nuclear magnetic resonance studies further supported similarity of three-dimensional structure and molecular dynamics of the peptide. Other methods, such as sedimentation velocity and size exclusion chromatography, demonstrated similarity in peptide aggregation state. These latter methods, in addition to reversed phase chromatography, were also employed for monitoring stability under forced degradation, and at the end of recommended shelf storage and patient use conditions. In all cases and for all methodologies employed, similarity to the RLD was observed with respect to extent of aggregation and other degradation processes. Finally, ELISA and bioassay data demonstrated similarity in biological properties. These investigations comprehensively demonstrate physicochemical similarity of Calcitonin Salmon Nasal Spray and the RLD, and should prove a useful illustration to pharmaceutical scientists developing alternative and/or generic peptide or protein products.

  3. The Effect of Alendronate and Intranasal Calcitonin Treatments on Bone Mineral Density in Men with Idiopathic Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2003-03-01

    Full Text Available The aim of this study was to compare the effect of alendronate and calcitonin treatments on bone mineral density (BMD in men with idiopathic osteoporosis. After performing a detailed clinical and laboratory assessment in order to eliminate secondary factors that can lead to osteoporosis, fifty-two men with idiopathic osteoporosis were randomly assigned to two groups: 28 patients in the first group received intranasal salmon calcitonin at a dosage of 200 IU/ day and they also received daily doses of 1000 mg calcium supplements. Twenty-four patients in the second group used 10 mg alendronate/day and 1000 mg calcium/day. DXA was used for the measurement of BMD of the lumbar spine and proximal femur before and after the study period. At the end of the treatment, alendronate produced significant increases in BMD at the lumbar spine (p0.05. When the groups were compared with each other, a significant increase in lumbar BMD was obtained in favor of alendronate treatment (p<0.05. In conclusion, alendronate seemed to be more effective than calcitonin, increasing both spinal and femoral BMD, for the treatment of idiopathic male osteoporosis.

  4. Imprinted ZnO nanostructure-based electrochemical sensing of calcitonin: a clinical marker for medullary thyroid carcinoma.

    Science.gov (United States)

    Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K

    2015-01-01

    The present work describes an exciting method for the selective and sensitive determination of calcitonin in human blood serum samples. Adopting the surface molecular imprinting technique, a calcitonin-imprinted polymer was prepared on the surface of the zinc oxide nanostructure. Firstly, a biocompatible tyrosine derivative as a monomer was grafted onto the surface of zinc oxide nanostructure followed by their polymerization on vinyl functionalized electrode surface by activator regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP) technique. Such sensor can predict the small change in the concentration of calcitonin in the human body and it may also consider to be as cost-effective, renewable, disposable, and reliable for clinical studies having no such cross-reactivity and matrix effect from real samples. The morphologies and properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry and chronocoulometry. The linear working range was found to be 9.99 ng L(-1) to 7.919 mg L(-1) and the detection limit as low as 3.09±0.01 ng L(-1) (standard deviation for three replicate measurements) (S/N=3).

  5. Synthesis, characterization and in vitro evaluation of a bone targeting delivery system for salmon calcitonin.

    Science.gov (United States)

    Bhandari, Krishna Hari; Newa, Madhuri; Uludag, Hasan; Doschak, Michael R

    2010-07-15

    Synthetic salmon Calcitonin (sCT) is currently used to treat and manage conditions associated with low bone mass, and elicits its antiresorptive effect by acting upon Calcitonin receptors (CTRs) located on bone-resorbing osteoclast cells. However, CTRs are also widely distributed in many non-skeletal tissues (such as kidney, brain, and lung), and the competitive uptake of available sCT amongst such CTRs likely reduces sCT availability for bone resident osteoclast cells, particularly if the drug is administered systemically and not specifically targeted to bone. Hence, the objective of this study was to synthesize and characterize a bisphosphonate (BP)-mediated bone targeting delivery system for sCT and to determine whether the bioactivity of sCT was retained after BP conjugation. BP-sCT conjugates were synthesized by initially reacting sCT with sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) in dimethyl formamide in the presence of triethylamine (TEA) at room temperature. Thiolated (Thiol)-BP was then reacted with the sCT-sulfo-SMCC conjugates to generate sCT-BP conjugates, which were purified by dialysis and assayed using the micro-BCA protein assay. Non-BP containing control sCT-Cysteine conjugates were also synthesized using the same procedure. Reactions were monitored and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF) analysis and Tris-Tricine SDS-PAGE. Conjugates were evaluated for in vitro bone mineral affinity using a hydroxyapatite binding test, for bone mineral specificity using different calcium salt binding affinity assays, and for continued sCT bioactivity after conjugation using an intracellular cAMP stimulation in human T47D breast cancer cells. Our results confirmed that BP-conjugated sCT exhibited significantly greater affinity and specificity for bone mineral over unmodified sCT, and that sCT-BP conjugates retained strong CT bioactivity after conjugation

  6. C reactive protein, calcitonin and D-dimer in patients of community acquired pneumonia

    Institute of Scientific and Technical Information of China (English)

    Xue-Lin Zhang; Zhen Wang; Shu-Hui Lv; Hai-Jun Jing; Jian-Yun Kang; Jian-Qing Zhao

    2016-01-01

    Objective:To investigate the clinical significance of C- reactive protein (CRP), calcitonin (PCT) and D- two (D-D) in community acquired pneumonia.Methods:A total of 102 patients with community-acquired pneumonia (CAP) admitted from March 2015- March 2016 as the research objects. A total of 5 mL peripheral venous blood of CAP patients (within 24 h of admission, before antibiotic therapy) were collected, and centrifuged to obtain serum. Immune turbidimetric method was used in determination of CRP and DD, immune fluorescence method was used for determination of PCT.Results:As grade increasing, the levels of CRP, PCT, D-D were increased gradually, with significant difference among different levels (P<0.05); CRP, PCT and D-D levels of severe group were significantly higher than those of non severe group (P<0.05); death group, CRP, PCT and D-D levels of death group were significantly higher than those of the survival group (P< 0.05).Conclusions:CRP, PCT, D-D levels have certain correlation with degree of severity. They can be used as important indicators to judge the severity of the disease, and predict the prognosis. High levels of CRP, PCT, D-D indicate severity of the disease and poor prognosis.

  7. The effects of synthetic salmon calcitonin on thyroid C and follicular cells in adult female rats

    Directory of Open Access Journals (Sweden)

    M. Manojlovic-Stojanoski

    2011-08-01

    Full Text Available Structural and morphometric features of thyroid C and follicular cells were studied in adult rat females after treatment with synthetic salmon calcitonin (CT. The animals were chronically treated with either a low (10 IU/kg b.w or a high (100 IU/kg b.w dose of CT. A stereological method was applied to determine the volume density and the number of immunoreactive C cells. The height and volume density of follicular epithelium, colloid, interstitium and the follicles (epithelium plus colloid, as well as the index of activation rate were calculated. A significant decrease in body weight, as well as the volume density of immunoreactive C cells and the number of C cells per mm2, was observed in rats treated with both doses of CT. The height and volume density of follicular epithelium and follicles, as well as the index of activation rate were significantly increased in the animals given the high CT dose, while the volume densities of colloid and interstitium were reduced. No significant changes in the examined morphometric parameters were detected after treatment with the low CT dose. According to these results it can be concluded that the structural features of thyroid C and follicular cells were affected by the high dose CT treatment in the opposite manner, while the low dose CT treatment influenced only C cells.

  8. Relationship between internalization and calcitonin-induced receptor loss in T 47D cells

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, D.M.; Martin, T.J.

    1984-07-01

    Exposure of T 47D human breast cancer cells to salmon calcitonin (sCT) resulted in a reduction of binding capacity for (/sup 125/I)iodo-sCT in washed cells. The reduction was both time and concentration dependent. Recovery of binding capacity in CT-pretreated T 47D cells occurred in the absence of CT, but was prevented by inhibitors of protein synthesis. Studies were carried out to determine the mechanism of CT-induced reduction of binding capacity. It was found that at 37/sup 0/ C sCT induced a time-dependent loss of cell surface receptors, so that initially the lost binding capacity was largely reclaimable by acid treatment, whereas after longer exposure to sCT, acid treatment was much less effective in regenerating binding capacity. The CT-induced reduction in binding capacity was not observed when cells were pretreated with sCT at 4 C or in the presence of inhibitors of cellular metabolic energy. These results are consistent with the view that initially CT-induced loss of CT receptors in T 47D cells is primarily due to occupancy of cell-surface receptors and later to a reduction in the concentration of cell-surface receptors mediated by an energy requiring internalization process involving the CT-receptor complex; reappearance of receptors requires new protein synthesis.

  9. Formulation and evaluation of novel reverse microemulsions containing salmon calcitonin in hydrofluoroalkane propellants.

    Science.gov (United States)

    Shan, Ziyun; Tan, Yinhe; Qin, Lingzhen; Li, Ge; Pan, Xin; Wang, Zhouhua; Yu, Xiu; Wang, Qinruo; Wu, Chuanbin

    2014-05-15

    To develop reverse microemulsion as a potential strategy for pulmonary delivery of salmon calcitonin (sCT) in HFA134a propellant of pressurized metered dose inhalers (pMDIs), pluronic P85 (P85) was chosen as the most appropriate surfactant to form microemulsions containing sCT. Formulation parameters, including the surfactant and ethanol content, water content, and sCT loading, were optimized to obtain two desired pMDI formulations A and B with clear and transparent appearance, Tyndall effect, good physical stability and aerosolization properties. Aerosolization properties of the optimized pMDIs were assessed by next generation impactor (NGI) and twin-stage impactor (TSI), and the dose of sCT in each stage was assayed by HPLC. The fine particle fraction (FPF) of formulations A and B were both at the range of approximately 28.0-36.0%. Cytotoxicity studies indicated the cell viability determined by MTT assay only slightly dropped when the A549 cells were exposed to the pMDI formulations. Pharmacological study performed on the male Wistar rats showed the intratracheal administration of the microemulsion pMDIs containing sCT exhibited similar but prolonged hypocalcemic activity compared with the intravenous injection of sCT solution. Therefore, such reverse microemulsions are potential for pulmonary delivery of therapeutic peptides using HFA-pMDIs.

  10. Colonic absorption of salmon calcitonin using tetradecyl maltoside (TDM) as a permeation enhancer.

    Science.gov (United States)

    Petersen, Signe Beck; Nielsen, Lisette Gammelgaard; Rahbek, Ulrik Lytt; Guldbrandt, Mette; Brayden, David J

    2013-03-12

    Calcitonin is used as a second line treatment of postmenopausal osteoporosis, but widespread acceptance is somewhat limited by subcutaneous and intranasal routes of delivery. This study attempted to enable intestinal sCT absorption in rats using the mild surfactant, tetradecyl maltoside (TDM) as an intestinal permeation enhancer. Human Caco-2 and HT29-MTX-E12 mucus-covered intestinal epithelial monolayers were used for permeation studies. Rat in situ intestinal instillation studies were conducted to evaluate the absorption of sCT with and without 0.1 w/v% TDM in jejunum, ileum and colon. TDM significantly enhanced sCT permeation across intestinal epithelial monolayers, most likely due to combined paracellular and transcellular actions. In situ, TDM caused an increased absolute bioavailability of sCT in rat colon from 1.0% to 4.6%, whereas no enhancement increase was observed in ileal and jejunal instillations. Histological analysis suggested mild perturbation of colonic epithelia in segments instilled with sCT and TDM. These data suggest that the membrane composition of the colon is different to the small intestine and that it is more amenable to permeation enhancement. Thus, formulations designed to release payload in the colon could be advantageous for systemic delivery of poorly permeable molecules.

  11. Preparation and in vitro-in vivo evaluation of salmon calcitonin-loaded polymeric nanoparticles.

    Science.gov (United States)

    Glowka, Eliza; Sapin-Minet, Anne; Leroy, Pierre; Lulek, Janina; Maincent, Philippe

    2010-01-01

    The aim of the study was to develop and characterize polymeric nanoparticles as a sustained release system for salmon calcitonin (sCT). Nanoparticles were prepared by a double emulsion solvent evaporation method using Eudragit RS and two types of a biodegradable poly(lactic-co-glycolic) copolymer (PLGA). It was demonstrated that sCT was incorporated into nanoparticles with encapsulation efficiencies in the range 69-83%. In vitro release studies, unconventionally conducted in 5% acetic acid, showed great differences in sCT release time profiles. Nanoparticles with fast release profile (Eudragit RS, PLGA/Eudragit RS) released 80-100% of the encapsulated drug within a few hours. In contrast, the sCT release from pure PLGA nanoparticles was very slow, incomplete and reached only 20% after 4 weeks. In vivo study, conducted in Wistar rats, proved that elevated serum sCT levels could be sustained for 3 days after subcutaneous administration of PLGA nanoparticles and the achieved bioavailability was increased compared to sCT solution.

  12. Study of the action of calcitonin by its effects on lead-induced hypercalcemia. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Talmage, R.V.; VanderWiel, C.J.

    1979-01-01

    Intravenous (i.v.) injection of lead acetate produces an immediate elevation in total plasma calcium and phosphate levels. This is due to the formation of calcium-phosphate compounds which can be removed by centrifugation at 25,000 x g. For this study, the effect of salmon calcitonin (CT) on these lead-induced plasma changes was studied. Intact male rats were injected i.v. with lead acetate 10 to 30 mg/kg. CT (0.1 to 0.2 mU/g) injected 30 min prior to lead modified the lead-induced plasma changes as follows: the concentration of lead remaining in plasma was statistically reduced. This was accompanied by a decrease in the amount of colloidal calcium-phosphate removed by ultracentrifugation and a corresponding decrease in the lead-induced elevation of total plasma calcium and phosphate levels. This action of CT was still effective in acutely nephrectomized rats. However, a 15-day pretreatment with a diphosphonate abolished the hypocalcemic effect of CT and also abolished the ability of CT to affect the lead-induced plasma changes. Finally, CT was ineffective if injected in as short a time period as 30 min after lead injection. It is concluded from these studs that CT causes a rapid sequestering of lead from plasma into specific sites in bone.

  13. An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.

    Science.gov (United States)

    Ryan, Sinéad M; McMorrow, Jason; Umerska, Anita; Patel, Hetal B; Kornerup, Kristin N; Tajber, Lidia; Murphy, Evelyn P; Perretti, Mauro; Corrigan, Owen I; Brayden, David J

    2013-04-28

    Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I.A. delivery.

  14. Metabolism of radioiodinated salmon calcitonin in rats. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Scarpace, P.J.; Neuman, W.F.; Raisz, L.G.

    1977-05-01

    Synthetic salmon calcitonin (CT) was iodinated by an electrolytic method. The iodinated hormone retained full biological activity as determined in both an in vivo and in vitro bioassay. The metabolism of this hormone was studied in rats of two different ages, 24 days and 8 months old. Two types of uptake were observed: Rapid accumulation followed by rapid loss or degradation, as represented by the liver, and sustained accumulation with slow degradation, as represented by the kidney and bone. The liver accumulated a large fraction of the dose in 1 minute. Most of this was degraded or gone by 10 min and nearly all by 30 min. The kidney was a primary target organ in terms of concentrating the hormone. Nearly 50% of the initially accumulated CT, however, remained undegraded 60 min post-injection. The bone, to a lesser extent, concentrated the hormone where 70% remained undegraded 60 min post-injection. The bone accumulated significantly less CT while the kidney and liver accumulated more in 8-month-old rats compared to 24-day-old rats. This suggests that the relative ineffectiveness of CT in older animals as a hypocalcemic agent may be due in part to the inability of the bone to accumulate available hormone.

  15. Expression of thyroglobulin and calcitonin in spontaneous thyroid gland tumors in the Han Wistar rat.

    Science.gov (United States)

    Pilling, Andrew M; Jones, Stewart A; Endersby-Wood, Helen J; McCormack, Nicola A M; Turton, John A

    2007-04-01

    Spontaneous follicular and C-cell tumors of the thyroid gland in the Han Wistar rat were examined using two morphologic procedures. Firstly, in situ hybridization (ISH) was used to localize thyroglobulin (TG) and calcitonin (CT) mRNAs. Secondly, the proteins for these markers were detected using immunohistochemistry (IHC). The aim was to study the morphology of the tumors and to examine the usefulness of TG and CT markers in the differential diagnosis of these lesions. Follicular tumors with cystic, papillary and follicular patterns showed relatively consistent expression of TG mRNA by ISH, thereby confirming the diagnostic value of this technique. However, no staining for TG markers was observed in solid lesions. In general, C-cell tumors comprised well-differentiated cells that continued to express CT mRNA and peptides even after embolic spread and metastasis. Therefore, the performance of either ISH or IHC for CT markers can be used for diagnostic confirmation. Additional features noted in C-cell tumors included the appearance of tumor emboli or metastases in association with small primary lesions (less than 5 average follicular diameters in size) and the presence of eosinophilic (amyloid-like) material showing immunopositivity for CT peptides. Finally, evidence is provided for the sequestration of TG protein by proliferating C-cells.

  16. Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

    Science.gov (United States)

    Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

    2002-01-01

    The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

  17. EXPRESSION OF CALCITONIN GENE-RELATED PEPTIDE IN FACIAL NERVE OF HEMIFACIAL SPASM

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the immunoreactivity of Calcitonin gene-related peptide (CGRP) in the facial nerve when Hemifacial Spasm is occurring. Methods The electrophysiological technique was used to explore abnormal muscle response (AMR) which was characteristic of Hemifacial Spasm.The animal models of Hemifacial Spasm in New Zealand white rabbits were established by compressing the main trunk of artificial demyelinated facial nerve with the temporal superficial artery. At 6 weeks after surgery, the facial nerves were taken from the experimental group and control one, the immunohistochemistry for CGRP using polyclonal antibody with ABC kit was performed in the facial nerves; at the same time, the observation for the facial nerves of light and transmission electron microscope was performed. Results The facial nerve demyelinated and the axons retrogressively changed, CGRP immunoreactive positive fibers were significantly detected in experimental groups; whereas this phenomenon was not found in control group. Conclusion CGRP can nutrien the injured facial nerve and plays an important role in the pathogenesis of Hemifacial Spasm.

  18. Comparison of Calcitonin Gene Related Peptide Level between Children with Dilated Cardiomyopathy and Control Group

    Directory of Open Access Journals (Sweden)

    Noormohammad Noori

    2015-06-01

    Full Text Available Background: Dilated cardiomyopathy is revealed with left ventricular dilatation and systolic dysfunction. Objectives: This study aimed to compare the children with dilated cardiomyopathy and control group regarding the level of Calcitonin Gene Related Peptide (CGRP and its relationship with echocardiography findings Patients and Methods: This case-control study was conducted on 37 children with dilated cardiomyopathy and free of any clinical symptoms and 37 healthy age- and sex-matched children referring to Ali-e-Asghar and Ali Ebne Abitaleb hospitals in Zahedan, Iran. After taking history, echocardiography was performed for both groups. The data were analyzed using the SPSS statistical software and appropriate statistical tests. Results: The two groups were significantly different regarding most of the echocardiographic parameters (P < 0.05. Also, a significant difference was found between the two groups concerning the mean CGRP levels (P = 0.001. Among echocardiographic parameters, CGRP was directly related to Interventricular Septal dimension in Systole (IVSS (P = 0.022, R = 0.375. However, no significant relationship was observed between CGRP level and Ross classification. Conclusions: The findings of this study showed an increase in CGRP serum levels in the case group. Besides, a direct correlation was observed between CGRP level and IVSS.

  19. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation.

    Science.gov (United States)

    Walsh, David A; Mapp, Paul I; Kelly, Sara

    2015-11-01

    Arthritis is the commonest cause of disabling chronic pain, and both osteoarthritis (OA) and rheumatoid arthritis (RA) remain major burdens on both individuals and society. Peripheral release of calcitonin gene-related peptide (CGRP) contributes to the vasodilation of acute neurogenic inflammation. Contributions of CGRP to the pain and inflammation of chronic arthritis, however, are only recently being elucidated. Animal models of arthritis are revealing the molecular and pathophysiological events that accompany and lead to progression of both arthritis and pain. Peripheral actions of CGRP in the joint might contribute to both inflammation and joint afferent sensitization. CGRP and its specific receptors are expressed in joint afferents and up-regulated following arthritis induction. Peripheral CGRP release results in activation of synovial vascular cells, through which acute vasodilatation is followed by endothelial cell proliferation and angiogenesis, key features of chronic inflammation. Local administration of CGRP to the knee also increases mechanosensitivity of joint afferents, mimicking peripheral sensitization seen in arthritic joints. Increased mechanosensitivity in OA knees and pain behaviour can be reduced by peripherally acting CGRP receptor antagonists. Effects of CGRP pathway blockade on arthritic joint afferents, but not in normal joints, suggest contributions to sensitization rather than normal joint nociception. CGRP therefore might make key contributions to the transition from normal to persistent synovitis, and the progression from nociception to sensitization. Targeting CGRP or its receptors within joint tissues to prevent these undesirable transitions during early arthritis, or suppress them in established disease, might prevent persistent inflammation and relieve arthritis pain.

  20. Substance P and Calcitonin Gene-Related Peptide: Key Regulators of Cutaneous Microbiota Homeostasis

    Science.gov (United States)

    N’Diaye, Awa; Gannesen, Andrei; Borrel, Valérie; Maillot, Olivier; Enault, Jeremy; Racine, Pierre-Jean; Plakunov, Vladimir; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G. J.

    2017-01-01

    Neurohormones diffuse in sweat and epidermis leading skin bacterial microflora to be largely exposed to these host factors. Bacteria can sense a multitude of neurohormones, but their role in skin homeostasis was only investigated recently. The first study focused on substance P (SP), a neuropeptide produced in abundance by skin nerve terminals. SP is without effect on the growth of Gram-positive (Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis) and Gram-negative (Pseudomonas fluorescens) bacteria. However, SP is stimulating the virulence of Bacillus and Staphylococci. The action of SP is highly specific with a threshold below the nanomolar level. Mechanisms involved in the response to SP are different between bacteria although they are all leading to increased adhesion and/or virulence. The moonlighting protein EfTu was identified as the SP-binding site in B. cereus and Staphylococci. In skin nerve terminals, SP is co-secreted with the calcitonin gene-related peptide (CGRP), which was shown to modulate the virulence of S. epidermidis. This effect is antagonized by SP. Identification of the CGRP sensor, DnaK, allowed understanding this phenomenon as EfTu and DnaK are apparently exported from the bacterium through a common system before acting as SP and CGRP sensors. Many other neuropeptides are expressed in skin, and their potential effects on skin bacteria remain to be investigated. Integration of these host signals by the cutaneous microbiota now appears as a key parameter in skin homeostasis. PMID:28194136

  1. Presence by radioimmunoassay of a calcitonin-like substance in porcine pituitary glands

    Energy Technology Data Exchange (ETDEWEB)

    Catherwood, B.D.; Deftos, L.J.

    1980-06-01

    We studied acidic acetone extracts of whole porcine pituitary glands for the presence of immunoreactive calcitonin (CT) using a porcine CT (pCT) RIA which did not react with other known pituitary hormones. Four preparations of porcine pituitary extract contained immunoreactive CT. Three of these displayed inhibition of binding parallel to that of authentic pCT in the pCT RIA and contained a single peak of immunoreactivity similar to pCT when studied by two different gel filtration chromatography systems. One preparation of porcine pituitary extract showed nonparallelism in RIA dose-dilution experiments and multiple immunoreactive species both similar to and larger than pCT on gel filtration in 6 M guanidine HCl. The effect of the reduction of disulfide bonds, followed by carboxymethylation of sulfhydryl groups, on immunoreactivity and apparent molecular size was similar for the CT-like substance in porcine pituitary extract and for authentic pCT. Preliminary immunohistological studies showed cytoplasmic staining in cells of the porcine adenohypophysis. These results demonstrate that the porcine pituitary gland contains a substance which has some of the immunochemical and biochemical properties of thyroidal pCT.

  2. Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

    Directory of Open Access Journals (Sweden)

    Norihisa Mikami

    Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

  3. 高效液相色谱法测定鲑鱼降钙素混悬型气雾剂的含量%Determination of Salmon Calcitonin in Salmon Calcitonin Suspension Aerosol by HPLC

    Institute of Scientific and Technical Information of China (English)

    吴涵; 陈龙楷; 单紫筠; 潘昕; 吴传斌

    2014-01-01

    Objectiv To establish a method for the content determination of salmon calcitonin in Salmon Calcitonin Suspension Aerosol. Methods The chromatographic column was the Phenomenex Jupiter 300 Å C18 column ( 250 mm × 4. 6 mm, 5μm ) . The mobile phase A was 0. 02 mol/L tetramethyl ammonium hydroxide solution ( pH=2. 5 ) and the mobile phase B was acetonitrile. The samples were determined with binary gradient elution at a flow rate of 1. 0 mL/min and the UV detection wavelength at 220 nm. The column temperature was at 40℃. Results There was a good linear relationship between the peak area and the salmon calcitonin concentra-tion within the range of 0. 8-50 μg/mL, and the regression equation was A=4. 508 7 × 104ρ-7. 394 8 × 103, r=0. 999 7 ( n=7). The average recovery rate was 98. 24%, RSD=1. 18%. The average content of salmon calcitonin in salmon calcitonin suspension Aerosol was 1. 41 mg. Conclusion The HPLC method is accurate, reliable, easy operation and suitable for the content determination of Salmon Calci-tonin Suspension Aerosol.%目的:建立测定鲑鱼降钙素混悬型气雾剂中鲑鱼降钙素含量的高效液相色谱法。方法采用Phenomenex Jupiter C18300Ù色谱柱(250 mm ×4.6 mm,5μm),流动相A(0.02 mol/L四甲基氢氧化铵,pH=2.5)、流动相B(乙腈)进行二元梯度洗脱,流速为1.0 mL/min,紫外检测波长为220 nm,柱温为40℃。结果鲑鱼降钙素质量浓度在0.8~50μg/mL范围内与峰面积成良好线性关系,回归方程为A=4.5087×104ρ-7.3948×103,r=0.9997( n=7),加样回收率为98.24%,RSD为1.18%。测得鲑鱼降钙素混悬型气雾剂中鲑鱼降钙素平均含量为每瓶1.41 mg。结论该法准确、可靠、操作简便,适用于鲑鱼降钙素混悬型气雾剂的含量测定。

  4. Benefit of measuring basal serum calcitonin to detect medullary thyroid carcinoma in a Danish population with a high prevalence of thyroid nodules

    DEFF Research Database (Denmark)

    Hasselgren, Martin; Hegedüs, Laszlo; Godballe, Christian

    2009-01-01

    ; thyroidectomy was performed in 307 of these patients. RESULTS: Thirty-nine patients had elevated serum calcitonin; 6 of these patients had MTC detected by the initial diagnostic setup. No additional patient in the cohort was registered in the Danish Thyroid Cancer Database, reflecting that all patients with MTC......BACKGROUND: Routine measurement of serum calcitonin to detect medullary thyroid carcinoma (MTC) continues to be fiercely debated, although less attention has been paid to the positive predictive value (PPV) of this method. METHODS: We collected data from 959 patients with nontoxic nodular goiter....... The low PPV might lead to unnecessary thyroid surgery. Thus, the result of serum calcitonin measurement should always be interpreted in the context of other clinical variables. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009....

  5. Imprinted ZnO nanostructure-based electrochemical sensing of calcitonin: A clinical marker for medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Patra, Santanu; Roy, Ekta [Department of Applied Chemistry, Indian School of Mines, Dhanbad, Jharkhand 826 004 (India); Madhuri, Rashmi, E-mail: rshmmadhuri@gmail.com [Department of Applied Chemistry, Indian School of Mines, Dhanbad, Jharkhand 826 004 (India); Sharma, Prashant K. [Functional Nanomaterials Research Laboratory, Department of Applied Physics, Indian School of Mines, Dhanbad, Jharkhand 826 004 (India)

    2015-01-01

    Highlights: • Molecular imprinting-based sensor for medullary thyroid carcinoma marker was developed. • ZnO nanostructure was used as a platform for synthesis of imprinted polymer. • Imprinted polymer was prepared by ARGET–ATRP method. • A novel and biocompatible tyrosine amino acid derivative was used as monomer. • Linear working range is found from 9.99 ng L{sup −1} to 7.919 mg L{sup −1} with LOD 3.09 ng L{sup −1}. - Abstract: The present work describes an exciting method for the selective and sensitive determination of calcitonin in human blood serum samples. Adopting the surface molecular imprinting technique, a calcitonin-imprinted polymer was prepared on the surface of the zinc oxide nanostructure. Firstly, a biocompatible tyrosine derivative as a monomer was grafted onto the surface of zinc oxide nanostructure followed by their polymerization on vinyl functionalized electrode surface by activator regenerated by electron transfer–atom transfer radical polymerization (ARGET–ATRP) technique. Such sensor can predict the small change in the concentration of calcitonin in the human body and it may also consider to be as cost-effective, renewable, disposable, and reliable for clinical studies having no such cross-reactivity and matrix effect from real samples. The morphologies and properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry and chronocoulometry. The linear working range was found to be 9.99 ng L{sup −1} to 7.919 mg L{sup −1} and the detection limit as low as 3.09 ± 0.01 ng L{sup −1} (standard deviation for three replicate measurements) (S/N = 3)

  6. Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

    Science.gov (United States)

    Kushlinskii, N E; Timofeev, Yu S; Solov'ev, Yu N; Gerstein, E S; Lyubimova, N V; Bulycheva, I V

    2014-08-01

    Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

  7. Uridine branch acceptor is a cis-acting element involved in regulation of the alternative processing of calcitonin/CGRP-l pre-mRNA.

    OpenAIRE

    Adema, G. J.; van Hulst, K L; Baas, P.D.

    1990-01-01

    The human calcitonin/CGRP-I (CALC-I) gene contains 6 exons and encodes two polypeptide precursors. In thyroid C-cells, calcitonin (CT) mRNA is produced by splicing of exons 1-2-3 to exon 4 (CT-encoding) and polyadenylation at exon 4. CGRP-I mRNA is produced in particular neural cells by splicing of exons 1-2-3 to exon 5 (CGRP-I-encoding) and the polyadenylated exon 6. We previously reported that model precursor RNAs containing the exon 3 to exon 5 region of the CALC-I gene are processed predo...

  8. Synthesis, characterization and evaluation of bone targeting salmon calcitonin analogs in normal and osteoporotic rats.

    Science.gov (United States)

    Bhandari, Krishna Hari; Newa, Madhuri; Chapman, Jillian; Doschak, Michael R

    2012-02-28

    In order to assess the therapeutic efficacy of an antiresorptive drug with imparted bone targeting potential using bisphosphonate (BP) conjugation and an improved pharmacokinetic profile using PEGylation, we synthesized, characterized and evaluated in vivo efficacy of bone-targeting PEGylated salmon calcitonin (sCT) analog (sCT-PEG-BP). sCT-PEG-BP was compared with non-PEGylated bone targeting sCT analog (sCT-BP) and unmodified, commercially available sCT. sCT-PEG-BP conjugates were characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis. The effect of PEG-BP or BP upon sCT secondary structure was examined by Circular Dichroism and sCT-PEG-BP was evaluated for in vitro bone mineral Hydroxyapatite (HA) binding ability and calcium salts specificity using a binding assay for bone HA and several calcium salts. Anti-calcitonin antibody binding ability of these analogs was determined using enzyme-linked immunosorbent assay (ELISA), by reacting bone targeting sCT analogs with calcium phosphate coated Osteologic® plates and detecting the bound sCT using anti-sCT antibody. Potential cytotoxicity of these compounds was evaluated in monocytic RAW 264.7 cells, and sCT bioactivity was evaluated using an in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. Finally, in vivo efficacy of each compound was evaluated by determining the plasma levels of calcium after s.c. administration in normal rats, and in a rat model of Osteoporosis, secondary to ovariectomy (OVX). In vivo micro-computed tomography (micro-CT) was used to temporally map and quantify alterations in bone volume and bone mineral density (BMD) in the same animals at 1, 4, 8 and 12 weeks after OVX surgery. Sixteen 6 week old virgin female rats underwent OVX surgery followed by the daily s.c. injection of 2.5IU/kg/day sCT or equivalent analogs, and compared to four sham-operated, placebo treated control rats. Our results showed the chemical coupling of

  9. Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

    DEFF Research Database (Denmark)

    Eftekhari, S; Salvatore, C A; Calamari, A;

    2010-01-01

    system and hence the potential antagonist sites of action remain unknown. Therefore we designed a study to evaluate the localization of CGRP and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP) 1 in the human trigeminal ganglion using...... immunohistochemistry and compare with that of rat. Antibodies against purified CLR and RAMP1 proteins were produced and characterized for this study. Trigeminal ganglia were obtained at autopsy from adult subjects and sections from rat trigeminal ganglia were used to compare the immunostaining pattern. The number...

  10. Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas

    DEFF Research Database (Denmark)

    Rasmussen, T N; Bersani, M; Schmidt, P;

    1998-01-01

    The aim of this study was to investigate the possible role of porcine calcitonin gene-related peptide (CGRP) in the regulation of the endocrine porcine pancreas. Initially, we isolated and purified CGRP from extracts of porcine adrenal glands and pancreases. A single molecular form of the peptide...... was found in the two tissues. The adrenal peptide was sequenced and found to differ from human alpha-CGRP at six positions and from human beta-CGRP at three positions. By immunohistochemistry, CGRP was found in nerve fibers in the pancreatic ganglia. A synthetic replica of the porcine peptide was infused...

  11. Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats.

    Science.gov (United States)

    Wei, Jinsong; Wang, Jian; Gong, Yan; Zeng, Rong

    2015-08-01

    The objective of the present study was to assess the effectiveness of combined salmon calcitonin (sCT) and aspirin [acetylsalicylic acid (ASA)] treatment in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Following 12 weeks of treatment, therapeutic efficacy was assessed by evaluating changes in the biochemical and biophysical properties of bone (n=8 rats per group). Serological markers of bone metabolism were measured by ELISA; bone mineral densities (BMD) by dual energy X-ray absorptiometry; bone biomechanics of the femur and lumbar vertebrae by three-point stress test; trabecular bone morphology of lumbar vertebrae by hematoxylin and eosin staining; messenger RNA expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow cells by reverse transcription-quantitative polymerase chain reaction and OPG and RANKL protein expression levels in the proximal tibia were analyzed by immunohistochemistry. Compared with treatment by sCT or ASA alone, combined treatment (sCT+ASA) increased BMD, improved femur bone strength, normalized trabecular network architecture and morphology, and increased mRNA and protein expression of OPG, while reducing the expression of RANKL. Collectively, these results demonstrated that combined treatment (sCT+ASA) of osteoporotic symptoms in OVX rats was more effective than treatment with sCT or ASA alone. Furthermore, these two drugs appeared to alter the expression of two distinct factors in the OPG/RANKL/RANK system, suggesting that their effects may be synergistic. Since sCT and ASA are currently approved for use in humans, the results of the present study suggest that the safety and efficacy of sCT+ASA combined therapy for post-menopausal osteoporosis should be assessed in clinical trials.

  12. PK/PD modelling of comb-shaped PEGylated salmon calcitonin conjugates of differing molecular weights.

    Science.gov (United States)

    Ryan, Sinéad M; Frías, Jesús M; Wang, Xuexuan; Sayers, Claire T; Haddleton, David M; Brayden, David J

    2011-01-20

    Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel comb-shaped end-functionalised (poly(PEG) methyl ether methacrylate) (sCT-P) polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E(max) and an EC(50) of 3.7nM. In vivo, while free sCT and the conjugates reduced serum [calcium] to a maximum of 15-30% over 240 min, the half-life (T(1/2)) was increased and the area under the curve (AUC) was extended in proportion to conjugate MW. Likewise, the polymer conferred protection on sCT against attack by trypsin, chymotrypsin, elastase, rat serum and liver homogenates, with the best protection afforded by sCT-P (40kDa). Mathematical modelling accurately predicted the MW relationships to in vitro efficacy, potency, in vivo PK and enzymatic stability. With a significant increase in T(1/2) for sCT, the 40kDa MW comb-shaped PEG conjugate of sCT may have potential as a long-acting injectable formulation.

  13. Evaluation of HPβCD-PEG microparticles for salmon calcitonin administration via pulmonary delivery.

    Science.gov (United States)

    Tewes, Frederic; Gobbo, Oliviero L; Amaro, Maria I; Tajber, Lidia; Corrigan, Owen I; Ehrhardt, Carsten; Healy, Anne Marie

    2011-10-03

    For therapeutic peptides, the lung represents an attractive, noninvasive route into the bloodstream. To achieve optimal bioavailability and control their fast rate of absorption, peptides can be protected by coprocessing with polymers such as polyethylene glycol (PEG). Here, we formulated and characterized salmon calcitonin (sCT)-loaded microparticles using linear or branched PEG (L-PEG or B-PEG) and hydroxypropyl-beta-cyclodextrin (HPβCD) for pulmonary administration. Mixtures of sCT, L-PEG or B-PEG and HPβCD were co-spray dried. Based on the particle properties, the best PEG:HPβCD ratio was 1:1 w:w for both PEGs. In the sCT-loaded particles, the L-PEG was more crystalline than B-PEG. Thus, L-PEG-based particles had lower surface free energy and better aerodynamic behavior than B-PEG-based particles. However, B-PEG-based particles provided better protection against chemical degradation of sCT. A decrease in sCT permeability, measured across Calu-3 bronchial epithelial monolayers, occurred when the PEG and HPβCD concentrations were both 1.6 wt %. This was attributed to an increase in buffer viscosity, caused by the two excipients. sCT pharmacokinetic profiles in Wistar rats were evaluated using a 2-compartment model after iv injection or lung insufflation. The maximal sCT plasma concentration was reached within 3 min following nebulization of sCT solution. L-PEG and B-PEG-based microparticles were able to increase T(max) to 20 ± 1 min and 18 ± 8 min, respectively. Furthermore, sCT absolute bioavailability after L-PEG-based microparticle aerosolization at 100 μg/kg was 2.3 times greater than for the nebulized sCT solution.

  14. Parathyroid hormone and calcitonin interactions in bone: Irradiation-induced inhibition of escape in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Krieger, N.S.; Tashjian, A.H. Jr.; Feldman, R.S.

    1982-01-01

    Calcitonin (CT) inhibits hormonally stimulated bone resorption only transiently in vitro. This phenomenon has been termed ''escape,'' but the mechanism for the effect is not understood. One possible explanation is that bone cell differentiation and recruitment of specific precursor cells, in response to stimulators of resorption, lead to the appearance of osteoclasts that are unresponsive to CT. To test this hypothesis, cell proliferation in neonatal mouse calvaria in organ culture was inhibited by irradiation from a cobalt-60 source. At a dose of 6000 R, (/sup 3/H)thymidine incorporation into intact calvaria was inhibited approximately 90%. Irradiation had no effect on the resorptive response to 0.1 U/ml parathyroid hormone (PTH). However, irradiation induced a dose-dependent inhibition of the escape response which was maximal at 6000 R. A dose of 6000 R did not affect the binding of /sup 125/I-salmon CT to calvaria and decreased PTH stimulation of cyclic AMP release from bone without affecting the cyclic AMP response to CT. Although irradiation caused a dose-dependent inhibition of DNA synthesis, the dose-response curves for that effect and inhibition of escape were not superimposable. A morphologic study of hormonally treated calvaria demonstrated that irradiation prevented the early increase in number of osteoclasts in PTH-treated calvaria that had been observed previously in unirradiated bones. Autoradiography showed that irradiation also prevented the PTH-stimulated recruitment of newly divided mononuclear cell precursors into osteoclasts. This may be correlated with the effect of irradiation to prevent the loss of responsiveness to CT in the presence of PTH.

  15. Oral salmon calcitonin improves fasting and postprandial glycemic control in lean healthy rats.

    Science.gov (United States)

    Feigh, M; Nielsen, R H; Hansen, C; Henriksen, K; Christiansen, C; Karsdal, M A

    2012-02-01

    A novel oral form of salmon calcitonin (sCT) was recently demonstrated to improve both fasting and postprandial glycemic control and induce weight loss in diet-induced obese and insulin-resistant rats. To further explore the glucoregulatory efficacy of oral sCT, irrespective of obesity and metabolic dysfunction, the present study investigated the effect of chronic oral sCT treatment on fasting and postprandial glycemic control in male lean healthy rats. 20 male rats were divided equally into a control group receiving oral vehicle or an oral sCT (2 mg/kg) group. All rats were treated twice daily for 5 weeks. Body weight and food intake were monitored during the study period and fasting blood glucose, plasma insulin and insulin sensitivity were determined and an oral glucose tolerance test (OGTT) performed at study end. Compared with the vehicle group, rats receiving oral sCT had improved fasting glucose homeostasis and insulin resistance, as measured by homeostatic model assessment of insulin resistance index (HOMA-IR), with no change in body weight or fasting plasma insulin. In addition, the rats receiving oral sCT had markedly reduced glycemia and insulinemia during OGTT. This is the first report showing that chronic oral sCT treatment exerts a glucoregulatory action in lean healthy rats, irrespective of influencing body weight. Importantly, oral sCT seems to exert a dual treatment effect by improving fasting and postprandial glycemic control and insulin sensitivity. This and previous studies suggest oral sCT is a promising agent for the treatment of obesity-related insulin resistance and type 2 diabetes.

  16. Preparation and characterization of salmon calcitonin-sodium triphosphate ionic complex for oral delivery.

    Science.gov (United States)

    Lee, Hea Eun; Lee, Min Jung; Park, Cho Rong; Kim, A Young; Chun, Kyung Hwa; Hwang, Hee Jin; Oh, Dong Ho; Jeon, Sang Ok; Kang, Jae Seon; Jung, Tae Sung; Choi, Guang Jin; Lee, Sangkil

    2010-04-19

    Even though salmon calcitonin (sCT) has been known as a potent hypocalcemic agent, only injection or nasal spray products are available on the market. In order to develop oral delivery system of the agent, a novel sCT-sodium tripolyphosphate (STPP) ionic complex was fabricated and also characterized. For the optimization of the ionic complexation, the effect of incubation time and molar ratio between sCT and STPP was evaluated. Particle size of the ionic complex in aqueous media, SEM images, DSC, FT-IR, in vitro release test, stability within the simulated intestinal fluid, and hypocalcemic effect were evaluated. The optimal molar complexation ratio of sCT to STPP was ranged from 1:5 to 1:10 and the complexation efficiency was about 95%. The SEM image has shown that the freeze dried ionic complex has rough morphology in their surface and the particle size in PBS (pH 7.4) was about 220nm. The DSC and FT-IR results provided evidences for ionic interaction between -NH(2) groups and -P horizontal lineO groups of sCT and STPP, respectively. The sCT ionic complex has shown sustained sCT releasing characteristics for 3weeks. The sCT-STPP ionic complex was protective to enzymatic attack and in vivo animal data revealed that the present ionic complex would show continuous hypocalcemic effect. Conclusively, the present sCT-STPP ionic complex formulation thought to be a novel oral delivery candidate for the treatment of osteoporosis.

  17. Improved intestinal delivery of salmon calcitonin by water-in-oil microemulsions.

    Science.gov (United States)

    Fan, Yating; Li, Xinru; Zhou, Yanxia; Fan, Chao; Wang, Xiaoning; Huang, Yanqing; Liu, Yan

    2011-09-15

    Therapeutic peptides are highly potent and specific in their functions, but difficulties in their oral administration require parallel development of viable delivery systems to improve their oral bioavailability. The objective of this study was to explore the feasibility of water-in-oil (w/o) microemulsions for improving the absorption of intraduodenally administered salmon calcitonin (sCT). The w/o microemulsions were prepared from medium chain triglyceride, Tween 80 and Span 80 or soybean phosphatidylcholine, propylene glycol and phosphate saline, and characterized by particle size and in vitro physical stability under dilution with different physiologically relevant diluents. The effects of addition of polymers such as hydroxypropylmethylcellulose and Carbomer into aqueous phase on the properties of microemulsions were assessed. sCT was efficiently encapsulated into microemulsions with nanoscaled diameter ranged from about 6 to 134nm. As expected from the non-ionic nature of the investigated microemulsions, the physical stability, evaluated by visual inspection, the particle size and leakage percent under dilution, was found to be unaffected by pH and/or ionic strength of diluents and it was opposite for the microemulsions with ionic components. In addition, the dilution extent had a pronounced effect on the physical stability of the diluted microemulsions. The effect of polymers added into aqueous phase of the microemulsions on the absorption of the drug entrapped in microemulsions with different components was investigated. The optimized microemulsions were shown to generate substantial enhancement (up to 4-fold) of relative pharmacological activity of sCT with regard to the control solution of the drug. This indicated that the w/o microemulsions could offer the potential to significantly improve intestinal absorption of sCT.

  18. Characterisation of salmon calcitonin in spray-dried powder for inhalation. Effect of chitosan.

    Science.gov (United States)

    Yang, M; Velaga, S; Yamamoto, H; Takeuchi, H; Kawashima, Y; Hovgaard, L; van de Weert, M; Frokjaer, S

    2007-03-01

    Salmon calcitonin (sCT) powders suitable for inhalation, containing chitosan and mannitol as absorption enhancer and protection agent, respectively, were prepared using a spray-drying process. The effect of chitosan on physicochemical stability of sCT in the dry powder was investigated by different analytical techniques. High-performance liquid chromatography (HPLC) analysis indicated that sCT was chemically stable upon spray-drying. With the proportion of chitosan in spray-drying formulation being increased, dissolution of sCT from the dry powders was decreased both in phosphate buffer and acetate buffer. The thioflavine T fluorescence assay showed that no fibrils were present in the spray-dried powder. However, sCT partly fibrillated in the phosphate buffer, but not in acetate buffer. Fourier transform infrared (FTIR) spectra showed that the secondary structure of sCT was slightly changed in the dry powder, yet no aggregate signal was observed. Circular dichroism analysis indicated that the structure of sCT in an aqueous formulation was slightly altered by addition of chitosan. Nevertheless, recovery of sCT was not influenced by chitosan in the aqueous formulation as indicated by HPLC analysis. This study suggested that sCT, in absence of any additives, was stable during the spray-drying process under certain conditions. Addition of chitosan affects recovery of sCT from spray-dried powders, which may be due to formation of a partially irreversible complex between the protein and chitosan during the spray-drying process.

  19. Identification and biological activity of ovine and caprine calcitonin receptor-stimulating peptides 1 and 2.

    Science.gov (United States)

    Charles, Christopher J; Katafuchi, Takeshi; Yandle, Timothy G; Minamino, Naoto

    2008-08-01

    We have recently reported the isolation of three new members of the calcitonin (CT) gene-related peptide family of peptides, the CT receptor (CT-R)-stimulating peptides (CRSPs). We now report the sequencing and characterization of ovine/caprine CRSP-1 and caprine CRSP-2. Mature ovine and caprine CRSP-1 are identical and have strong structural homology to CRSP-1s identified to date from other species. As with other CRSP-1s, ovine/caprine CRSP-1 binds to and activates the CT-R but not the CT-like receptor (CL-R) in combination with the receptor activity-modifying proteins (RAMPs). By contrast, caprine CRSP-2 does not activate any of these receptor-RAMP complexes. Intravenous infusions of ovine CRSP-1 to normal conscious sheep induced dose-dependent reduction in plasma total Ca levels (P=0.02) and corrected Ca levels (P=0.017) associated with increases in plasma cAMP (P=0.002). CRSP-1 reduced both plasma amino-terminal pro-C-type natriuretic peptide levels (P=0.006) and plasma renin activity (P=0.028). There were no significant effects observed on hemodynamic or renal indices measured. In conclusion, we have sequenced ovine/caprine CRSP-1 and caprine CRSP-2 precursors. This newly identified CRSP-1 has been shown to share the structural and biological features of CRSP-1s known to date. In vivo studies confirm that ovine CRSP-1 reduces plasma Ca levels in sheep, presumably via a cAMP-mediated mechanism. By contrast, caprine CRSP-2 did not stimulate any combination of CT-R, CL-R, and RAMPs. Accession numbers of cDNA determined in this study are caprine CRSP-1, AB364646; caprine CRSP-2, AB364647; and ovine CRSP-1, AB364648.

  20. Design and evaluation of poly(DL-lactic-co-glycolic acid) nanocomposite particles containing salmon calcitonin for inhalation.

    Science.gov (United States)

    Yang, Mingshi; Yamamoto, Hiromitsu; Kurashima, Homare; Takeuchi, Hirofumi; Yokoyama, Toyokazu; Tsujimoto, Hiroyuki; Kawashima, Yoshiaki

    2012-08-15

    Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion(TM) technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs.

  1. Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid haemorrhage

    Directory of Open Access Journals (Sweden)

    Stelios eKokkoris

    2012-11-01

    Full Text Available Calcitonin gene-related peptide (CGRP is one of the most potent microvascular vasodilators identified to date. Vascular relaxation and vasodilation is mediated via activation of the CGRP receptor. This atypical receptor is made up of a G-protein-coupled receptor called calcitonin receptor-like receptor (CLR, a single transmembrane protein called receptor activity-modifying protein (RAMP, and an additional protein that is required for Gas coupling, known as receptor component protein (RCP. Several mechanisms involved in CGRP mediated relaxation have been identified. These include nitric oxide (NO-dependent endothelium-dependent mechanisms or cAMP-mediated endothelium-independent pathways; the latter being more common. Subarachnoid haemorrhage (SAH is associated with cerebral vasoconstriction that occurs several days after the haemorrhage and is often fatal. The vasospasm occurs in 30–40% of patients and is the major cause of death from this condition. The vasoconstriction is associated with a decrease in CGRP levels in nerves and an increase in CGRP levels in draining blood, suggesting that CGRP is released from nerves to oppose the vasoconstriction. This evidence has led to the concept that exogenous CGRP may be beneficial in a condition that has proven hard to treat. The present article reviews: a the pathophysiology of delayed ischaemic neurologic deficit after SAH b the basics of the CGRP receptor structure, signal transduction and vasodilatation mechanisms and c the studies that have been conducted so far using CGRP in both animals and humans with SAH.

  2. Early stages of salmon calcitonin aggregation: effect induced by ageing and oxidation processes in water and in the presence of model membranes.

    Science.gov (United States)

    Gaudiano, Maria Cristina; Colone, Marisa; Bombelli, Cecilia; Chistolini, Pietro; Valvo, Luisa; Diociaiuti, Marco

    2005-06-30

    The natural ageing- and hydrogen peroxide-induced aggregation of salmon calcitonin were studied in water and in the presence of dipalmitoylphosphatidylcholine (DPPC) liposomes. The early stages of the aggregation process at low protein concentration were investigated by means of Circular Dichroism spectroscopy (CD) and conventional and immunogold labelling Transmission Electron Microscopy (TEM). In buffered water solution, salmon calcitonin showed a two-stage conformational variation related to fibril formation and phase-separation of larger aggregates. A first stage, characterised by small conformational changes but a decrease in dichroic band intensity, was followed by a second stage, 6 days after, leading to higher conformational variations and aggregations. Salmon calcitonin showed a distinct modification in the secondary structure and aggregate morphology in the presence of hydrogen peroxide with respect to natural ageing, indicating that the two aggregation processes (natural and chemical-induced) followed a distinct mechanism. The oxidised forms of the peptide were separated by liquid chromatography. The same study was performed in the presence of DPPC liposomes. The results obtained by conventional and immunogold labelling TEM evidenced that salmon calcitonin in buffered water solution essentially does not enter the liposomes but forms around them a fibril network characterised by the same conformational changes after 6 days. The oxidised sample in the presence of liposomes showed a "fibrils hank", separated from liposomes. The presence of liposomes did not affect either the aggregation or the conformational modifications yet observed by TEM and CD in water solution.

  3. Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri;

    2014-01-01

    Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP...

  4. Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related Peptide-induced cerebral reactivity

    DEFF Research Database (Denmark)

    Chadha, Preet S; Jepps, Thomas A; Carr, Georgina;

    2014-01-01

    Middle cerebral artery (MCA) diameter is regulated by inherent myogenic activity and the effect of potent vasodilators such as calcitonin gene-related peptide (CGRP). Previous studies showed that MCAs express KCNQ1, 4, and 5 potassium channel genes, and the expression products (Kv7 channels) part...

  5. An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

    DEFF Research Database (Denmark)

    Smillie, Sarah-Jane; King, Ross; Kodji, Xenia;

    2014-01-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms...

  6. Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C

    2009-01-01

    Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity...

  7. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  8. De novo sequencing of two novel peptides homologous to calcitonin-like peptides, from skin secretion of the Chinese Frog, Odorrana schmackeri

    Directory of Open Access Journals (Sweden)

    Geisa P.C. Evaristo

    2015-09-01

    Full Text Available An MS/MS based analytical strategy was followed to solve the complete sequence of two new peptides from frog (Odorrana schmackeri skin secretion. This involved reduction and alkylation with two different alkylating agents followed by high resolution tandem mass spectrometry. De novo sequencing was achieved by complementary CID and ETD fragmentations of full-length peptides and of selected tryptic fragments. Heavy and light isotope dimethyl labeling assisted with annotation of sequence ion series. The identified primary structures are GCD[I/L]STCATHN[I/L]VNE[I/L]NKFDKSKPSSGGVGPESP-NH2 and SCNLSTCATHNLVNELNKFDKSKPSSGGVGPESF-NH2, i.e. two carboxyamidated 34 residue peptides with an aminoterminal intramolecular ring structure formed by a disulfide bridge between Cys2 and Cys7. Edman degradation analysis of the second peptide positively confirmed the exact sequence, resolving I/L discriminations. Both peptide sequences are novel and share homology with calcitonin, calcitonin gene related peptide (CGRP and adrenomedullin from other vertebrates. Detailed sequence analysis as well as the 34 residue length of both O. schmackeri peptides, suggest they do not fully qualify as either calcitonins (32 residues or CGRPs (37 amino acids and may justify their classification in a novel peptide family within the calcitonin gene related peptide superfamily. Smooth muscle contractility assays with synthetic replicas of the S–S linked peptides on rat tail artery, uterus, bladder and ileum did not reveal myotropic activity.

  9. Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

    Directory of Open Access Journals (Sweden)

    Patrícia Severo do Nascimento

    2012-09-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

  10. Comparison of reversible and nonreversible aqueous-soluble lipidized conjugates of salmon calcitonin.

    Science.gov (United States)

    Cheng, Weiqiang; Lim, Lee-Yong

    2008-01-01

    Reversible aqueous lipidization (REAL) at the interdisulfide bond has been shown to improve the deliverability of some peptide drugs. Recently, we developed a nonreversible aqueous lipidization method targeted at the interdisulfide bond of salmon calcitonin (sCT). The resultant derivative had comparable hypocalcemic activity to sCT after subcutaneous injection in rats, despite possessing significantly different biophysical properties. The purpose of this study was to conduct a comparative evaluation of the biophysical properties of the reversible aqueous-soluble lipidized sCT (REAL-sCT) and its corresponding nonreversible aqueous-soluble compound (Mal-sCT) with a view to correlate these properties to the bioactivities of the peptides. REAL-sCT and Mal-sCT were successfully synthesized, purified and identified. Both conjugates showed comparable retention times in a C-18 HPLC column, as well as robust helical structures and aggregation behavior in water, although REAL-sCT was shown by dynamic light scattering experiments to form larger aggregates than Mal-sCT in water. The larger particle size of REAL-sCT correlated with its stronger resistance to degradation by intestinal enzymes. Unlike Mal-sCT, REAL-sCT was rapidly converted to sCT in liver juice; however, the regenerated sCT appeared to degrade at a slower rate than unmodified sCT in the liver juice. Compared with sCT, REAL-sCT after subcutaneous injection as an aqueous solution at a dose of 0.15 mg/kg produced a prolonged hypocalcemic activity that lasted at least 24 h in the rat. Using a novel LC-MS/MS method that was developed for this study, we were able to show concomitant increases in REAL-sCT and sCT plasma concentrations with time, the latter prevailing at 10% the molar concentration of the former. In contrast, sCT was not present in the plasma following the subcutaneous injection of Mal-sCT, although a comparable hypocalcemic activity with shorter duration was observed. Oral administration of REAL

  11. Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement.

    Science.gov (United States)

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon; Strauss, Holger M; Rahbek, Ulrik L; Andresen, Thomas L

    2015-10-01

    Acylation of peptide drugs with fatty acid chains has proven beneficial for prolonging systemic circulation, as well as increasing enzymatic stability and interactions with lipid cell membranes. Thus, acylation offers several potential benefits for oral delivery of therapeutic peptides, and we hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate its influence on intestinal cell translocation and membrane interaction. We find that acylation drastically increases in vitro intestinal peptide flux and confers a transient permeability enhancing effect on the cell layer. The analogues permeabilize model lipid membranes, indicating that the effect is due to a solubilization of the cell membrane, similar to transcellular oral permeation enhancers. The effect is dependent on pH, with larger effect at lower pH, and is impacted by acylation chain length and position. Compared to the unacylated peptide backbone, N-terminal acylation with a short chain provides 6- or 9-fold increase in peptide translocation at pH 7.4 and 5.5, respectively. Prolonging the chain length appears to hamper translocation, possibly due to self-association or aggregation, although the long chain acylated analogues remain superior to the unacylated peptide. For K(18)-acylation a short chain provides a moderate improvement, whereas medium and long chain analogues are highly efficient, with a 12-fold increase in permeability compared to the unacylated peptide backbone, on par with currently employed oral permeation enhancers. For K(18)-acylation the medium chain acylation appears to be optimal, as elongating the chain causes greater binding to the cell membrane but similar permeability, and we speculate that increasing the chain length further may

  12. Calcitonin gene-related peptide (CGRP) regulates excitability and refractory period of the guinea pig ureter.

    Science.gov (United States)

    Maggi, C A; Giuliani, S

    1994-08-01

    Previous studies have indicated that calcitonin gene-related peptide (CGRP), released from the peripheral endings of capsaicin-sensitive primary afferent neurons, may play a role as an inhibitory transmitter in the guinea pig ureter. The aim of this study was to compare the effect of capsaicin desensitization and administration of a CGRP receptor antagonist on the excitability and refractory period of the guinea pig ureter to electrical field stimulation. Electrical field stimulation using a long (5 msec.) pulse width produced phasic contractions of the ureter which were unaffected by tetrodotoxin, that is, were produced through direct excitation of ureteral smooth muscle. Human alpha CGRP (1 to 10 nM.) produced a concentration-dependent transient suppression of the evoked contractions, and its effect was prevented by the CGRP receptor antagonist human alpha CGRP(8-37) (1 microM.). In vitro capsaicin pretreatment (10 microM. for 15 minutes) to block neuropeptide release from peripheral endings of sensory nerves or administration of the CGRP receptor antagonist enhanced the responsiveness of the guinea pig ureter to electrical stimulation. In control ureters, the application of two trains of electrical stimuli failed to produce a second contraction at intertrain intervals greater than 20 seconds. The intertrain interval required to obtain a second contraction averaging 50% of the amplitude of the first response (ITI50) of control ureters was about 50 seconds. In vitro capsaicin pretreatment or administration of the CGRP receptor antagonist reduced the refractory period of the ureter to electrical field stimulation: ITI50 averaged 8.8 and 9.1 seconds after capsaicin or CGRP antagonist pretreatment, respectively. These findings demonstrate that capsaicin pretreatment or blockade of CGRP receptors produced qualitatively and quantitatively similar excitatory effects on ureteral excitability and refractory period and are in general agreement with the idea that CGRP is a

  13. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

    DEFF Research Database (Denmark)

    Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.

    2008-01-01

    g/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V-mean) in the middle cerebral artery (MCA), as well as the heart......Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (h alpha CGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of haCGRP (2 mu...

  14. Application of shock waves to rat skin decreases calcitonin gene-related peptide immunoreactivity in dorsal root ganglion neurons.

    Science.gov (United States)

    Takahashi, Norimasa; Wada, Yuichi; Ohtori, Seiji; Saisu, Takashi; Moriya, Hideshige

    2003-09-30

    There have been several reports on the use of extracorporeal shock waves in the treatment of pseudarthrosis, calcifying tendinitis, and tendinopathies of the elbow. However, the pathomechanism of pain relief has not been clarified. To investigate the analgesic properties of shock wave application, we analyzed changes in calcitonin gene-related peptide (CGRP)-immunoreactive (ir) dorsal root ganglion (DRG) neurons. In the nontreated group, fluorogold-labeled dorsal root ganglion neurons innervating the most middle foot pad of hind paw were distributed in the L4 and L5 dorsal root ganglia. Of these neurons, 61% were CGRP-ir. However, in the shock wave-treated group, the percentage of FG-labeled CGRP-ir DRG neurons decreased to 18%. These data show that relief of clinical pain after shock wave application may result from reduced CGRP expression in DRG neurons.

  15. Occurrence of substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide in dermographism and cold urticaria.

    Science.gov (United States)

    Wallengren, J; Möller, H; Ekman, R

    1987-01-01

    Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were assayed in lesions and normal skin of patients with dermographism and cold urticaria utilizing suction-induced blisters. There was no difference in SP and VIP concentrations between challenged and control skin of urticaria patients. On the whole, however, the concentration of both neuropeptides, and VIP in particular, was higher in the urticaria patients than in control subjects. CGRP levels were not increased. SP and VIP in blood samples from veins draining challenged skin areas were below the detection limit. It is concluded that SP and VIP may potentiate histamine in wheal formation and thus contribute to the increased reactivity of the skin to trauma and temperature changes in patients with physical urticaria.

  16. Formulation, stability and pharmacokinetics of sugar-based salmon calcitonin-loaded nanoporous/nanoparticulate microparticles (NPMPs) for inhalation.

    Science.gov (United States)

    Amaro, Maria Inês; Tewes, Frederic; Gobbo, Oliviero; Tajber, Lidia; Corrigan, Owen I; Ehrhardt, Carsten; Healy, Anne Marie

    2015-04-10

    A challenge exists to produce dry powder inhaler (DPI) formulations with appropriate formulation stability, biological activity and suitable physicochemical and aerosolisation characteristics that provide a viable alternative to parenteral formulations. The present study aimed to produce sugar-based nanoporous/nanoparticulate microparticles (NPMPs) loaded with a therapeutic peptide - salmon calcitonin (sCT). The physicochemical properties of the powders and their suitability for pulmonary delivery of sCT were determined. Production of powders composed of sCT loaded into raffinose or trehalose with or without hydroxypropyl-β-cyclodextrin was carried out using a laboratory scale spray dryer. Spray dried microparticles were spherical, porous and of small geometric size (≤2 μm). Aerodynamic assessment showed that the fine particle fraction (FPF) less than 5 μm ranged from 45 to 86%, depending on the formulation. The mass median aerodynamic diameter (MMAD) varied between 1.9 and 4.7 μm. Compared to unprocessed sCT, sCT:raffinose composite systems presented a bioactivity of approximately 100% and sCT:trehalose composite systems between 70-90% after spray drying. Storage stability studies demonstrated composite systems with raffinose to be more stable than those containing trehalose. These sugar-based salmon calcitonin-loaded NPMPs retain reasonable sCT bioactivity and have micromeritic and physicochemical properties which indicate their suitability for pulmonary delivery. Formulations presented a similar pharmacokinetic profile to sCT solution. Hence the advantage of a dry powder formulation is its non-invasive delivery route and ease of administration of the sCT.

  17. CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors.

    Science.gov (United States)

    Evans, B N; Rosenblatt, M I; Mnayer, L O; Oliver, K R; Dickerson, I M

    2000-10-06

    It is becoming clear that receptors that initiate signal transduction by interacting with G-proteins do not function as monomers, but often require accessory proteins for function. Some of these accessory proteins are chaperones, required for correct transport of the receptor to the cell surface, but the function of many accessory proteins remains unknown. We determined the role of an accessory protein for the receptor for calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide. We have previously shown that this accessory protein, the CGRP-receptor component protein (RCP), is expressed in CGRP responsive tissues and that RCP protein expression correlates with the biological efficacy of CGRP in vivo. However, the function of RCP has remained elusive. In this study stable cell lines were made that express antisense RCP RNA, and CGRP- and adrenomedullin-mediated signal transduction were greatly reduced. However, the loss of RCP did not effect CGRP binding or receptor density, indicating that RCP did not behave as a chaperone but was instead coupling the CGRP receptor to downstream effectors. A candidate CGRP receptor named calcitonin receptor-like receptor (CRLR) has been identified, and in this study RCP co-immunoprecipitated with CRLR indicating that these two proteins interact directly. Since CGRP and adrenomedullin can both signal through CRLR, which has been previously shown to require a chaperone protein for function, we now propose that a functional CGRP or adrenomedullin receptor consists of at least three proteins: the receptor (CRLR), the chaperone protein (RAMP), and RCP that couples the receptor to the cellular signal transduction pathway.

  18. Direct interactions between calcitonin-like receptor (CLR) and CGRP-receptor component protein (RCP) regulate CGRP receptor signaling.

    Science.gov (United States)

    Egea, Sophie C; Dickerson, Ian M

    2012-04-01

    Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling.

  19. Evaluation of /sup 99m/Tc diphosphonate kinetics and bone scans in patients with Paget's disease before and after calcitonin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Waxman, A.D.; Ducker, S.; McKee, D.; Siemsen, J.K.; Singer, F.R.

    1977-12-01

    Eleven patients with Paget's disease of bone underwent serial total body bone scans before and after therapy with calcitonin. All patients studied showed improvement clinically as well as biochemically. Scan improvement was noted in patients with mild disease. Patients with severe disease showed either no change or only slight improvement on the serial bone scans. The scan was of greatest value in determining the extent of disease, especially in 3 patients in whom biochemical values were normal. A single pulse injection of 50 M.R.C. units of salmon calcitonin produced a significant increase in the blood clearance of /sup 99m/Tc diphosphonate. The mechanism of this effect is not clear from this study.

  20. İdiopatik-post menopozal-senil osteoporozun ağrılı akut epizodlarının calcitonin ile tedavisi

    OpenAIRE

    Kokino, Siranus

    2004-01-01

    Bakırköy Fizik Tedavi ve Rehabilitasyon Merkezi'nde yapmış olduğumuz idiopatik veya sekonder osteoporozun ağrılı akut epizodlarının Salmon-Calcitonin tedavisi ile ilgili çalışmamız 31'i kadın 2'si erkek, 33 hasta üzerinde incelenmiştir. Deneklerimize çalışma süresi boyunca klinik tablonun şiddetine ve hastanın ilaca toleransına göre günlük 50100 UI Salmon Calcitonin tedavisi uygulanmıştır. İlacın çalışma süresince laboratuar parametrelerde anlamlı bir değişme saptanmamış, fonksiyonel yetm...

  1. Oral absorption enhancement of salmon calcitonin by using both N-trimethyl chitosan chloride and oligoarginines-modified liposomes as the carriers.

    Science.gov (United States)

    Huang, Aiwen; Su, Zhigui; Li, Sai; Sun, Minjie; Xiao, Yanyu; Ping, Qineng; Deng, Yanping

    2014-08-01

    In this study both N-trimethyl chitosan chloride (TMC) and oligoarginine (Arg8) were utilized to modify liposomes as the multifunctional carriers (TMC-Arg8-Lips) for enhancing the oral absorption of salmon calcitonin. Two permeation enhancers with positive charges were sequentially adsorbed on the liposomal surface with negative charges by electrostatic interaction. Instead of salmon calcitonin, fluorescein isothiocyanate dextran (FD4) was loaded in TMC-Arg8-Lips for Caco-2 cell permeation test in vitro and penetration examination in rat intestinal tract in vivo. The results showed that the apparent permeability coefficient (Papp) of TMC-Arg8-Lips containing FD4 were 7.0-, 4.4-, 1.8- and 1.4-folds higher than FD4 solution, FD4-TMC solution, non-modified liposomes (Non-Lips) and TMC modified liposomes (TMC-Lips), respectively. A strong fluorescence was observed by confocal laser scanning microscope (CLSM) at rat intestinal wall isolated in different times after the FD4 loaded carriers were intragastrically administrated. Furthermore, the images revealed that TMC-Arg8-Lips could penetrate deeply inside the mucosal membrane. The pharmacodynamic study indicated that TMC-Arg8-Lips containing calcitonin were more efficient in enhancing the absorption and prolonging the reduction of blood calcemia in rats. The area above the plasma calcium concentration-time curve (AAC) of TMC-Arg8-Lips containing calcitonin was increased by more than 16.6- and 1.6-fold when compared to Non-Lips and TMC-Lips, respectively.

  2. Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C

    2009-01-01

    Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity...... antagonism results in success in the acute treatment of migraine in only a certain fraction of the patients....

  3. 离子导入对降钙素经皮促渗作用的研究%Research on the Role of Iontophoresis in Calcitonin Percutaneous Penetration

    Institute of Scientific and Technical Information of China (English)

    王双侠; 魏雅冬; 戴明

    2011-01-01

    To improve biological macromolecules transdennal therapeutic drug concentration, peptide drug salmon calcitonin is taken as a model of biological drugs, the impact of iontophoresis and chemical penetration enhancers on percutaneous penetration of salmon calcitonin is studied. Dualchamber diffusion cells methods are adopted to investigate transdermal penetration effect of iontophoresis, Azone chemical penetration enhancers and iontophoresis - Azone and use of salmon calcitonin.%为了提高大分子生物药经皮给药的治疗浓度,以多肽类生物药鲑降钙素为模型药物,研究离子导入法和化学促渗剂对鲑降钙素经皮渗透的影响:利用水平双室扩散池的方法,考察了离子导入法、化学促渗剂氮酮以及离子导入-氯酮并用对鲑降钙素经皮渗透的促渗作用.

  4. Effect of Qianggu Capsule combined with salmon calcitonin injection treatment on bone mineral density and bone metabolism in patients with senile osteoporotic compression fractures

    Institute of Scientific and Technical Information of China (English)

    Li Li; Yu Si

    2016-01-01

    Objective:To analyze the effect of Qianggu Capsule combined with salmon calcitonin injection treatment on bone mineral density and bone metabolism in patients with senile osteoporotic compression fractures.Methods: A total of 92 cases of patients with senile osteoporotic compression fractures were divided into observation group and control group (n=46) according to random number table, control group received Qianggu Capsule treatment alone, observation group received Qianggu Capsule combined with salmon calcitonin injection treatment, and the differences in bone mineral density, bone metabolism indexes and CT-related parameters were compared between two groups.Results: BMD values of observation group after 3 courses and 6 courses of treatment were higher than those of control group; serum BGP and PTH values of observation group after treatment were higher than those of control group, CICP and CTX-Ⅰ values were lower than those of control group, and urine D-Pyr value was lower than that of control group; CV and CV/MV values of observation group after treatment were higher than those of control group, and MV value was lower than that of control group.Conclusion: Qianggu Capsule combined with salmon calcitonin injection can inhibit the disease progression in patients with senile osteoporotic compression fractures, optimize bone metabolism and promote osteogenesis, and it has positive clinical significance.

  5. Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery

    Directory of Open Access Journals (Sweden)

    Sinsuebpol C

    2013-08-01

    Full Text Available Chutima Sinsuebpol, Jittima Chatchawalsaisin, Poj Kulvanich Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand Purpose: The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs with mannitol and investigate pulmonary absorption in rats. Methods: The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. Results: sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. Conclusion: The sCT-CS-NPs with mannitol based spray dried powders were

  6. 降钙素基因相关肽受体组分蛋白%Researches of calcitonin gene-related peptide receptor component protein

    Institute of Scientific and Technical Information of China (English)

    唐江琼; 秦旭平

    2011-01-01

    降钙素基因相关肽受体组分蛋白(calcitonin gene-related peptide-receptor component protein,CGRP-RCP)是降钙素基因相关肽受体的一个具有146/148个氨基酸的胞内膜周边蛋白,特异地与降钙素受体样受体(calcitonin receptor-like receptor,CRLR)相互作用并促进CGRP和肾上腺髓质素的信号跨膜转导,现认为CGRP-RCP也是G蛋白偶联受体中一个动态的调节器.CGRP-RCP的mRNA在人和鼠的几乎所有组织均可检测到,在小鼠睾丸中分布尤其明显.在哺乳动物中,CGRP-RCP与C17(酵母菌中聚合酶Ⅲ的必需亚基)是直系同源蛋白,人体的CGRP-RCP能取代酵母中的C17,发挥与Cl7相同的生物学作用.%Calcitonin gene-related peptide receptor component protein (CGRP-RCP), an additional accessory protein of the calcitonin gene-related peptide receptor and an intracellular peripheral membrane protein, is composed of 146-148 residues, which interacts specifically with the calcitonin receptor-like receptor (CRLR) and facilitates signal transduction by CGRP and adrenomedullin.Furthermore, CGRP-RCP is a dynamic regulator of G protein-coupled signal transduction, and implies an additional level of receptor regulation unique to the CGRP system. The CGRP-RCP mRNA is expressed in all tissues of the human and mice, especially more in the testis of mice. Moreover, CGRP-RCP is the mammalian orthologue of C 17 (an essential subunit of yeast RNA polymerase) and human RCP could functionally replace its orthologue in yeast.

  7. A new method to increase selectivity of transglutaminase mediated PEGylation of salmon calcitonin and human growth hormone.

    Science.gov (United States)

    Mero, Anna; Schiavon, Mariano; Veronese, Francesco M; Pasut, Gianfranco

    2011-08-25

    Modification of therapeutic proteins and peptides by polyethylene glycol (PEG) conjugation is a well-known approach to improve the pharmacological properties of drugs. Several chemical procedures of PEG coupling are already in use but an alternative method based on microbial transglutaminase (mTGase) was recently devised. The enzyme catalyzes the link of mPEG-NH(2) to glutamines (Gln) of a substrate protein. In this case the advantage resides in the fact that usually only few Gln(s) in a protein are substrate of mTGase. In order to further restrict the selectivity of the enzyme, we investigated a new approach leading to the formation of a single conjugate isomer as well as for those proteins containing two or more Gln(s) as mTGase substrates. It was found that the addition of co-solvents in the reaction mixture influenced both the secondary structure of the targeted protein and the mTGase activity. The enzymatic PEGylation under these conditions yielded only mono- and selectively modified conjugates. The method was investigated with salmon calcitonin (sCT) and human growth hormone (hGH). In the case of sCT we also demonstrated the importance of site-selective conjugation for the preservation of in vivo activity.

  8. The slowly aggregating salmon Calcitonin: a useful tool for the study of the amyloid oligomers structure and activity.

    Science.gov (United States)

    Diociaiuti, Marco; Gaudiano, Maria Cristina; Malchiodi-Albedi, Fiorella

    2011-01-01

    Amyloid proteins of different aminoacidic composition share the tendency to misfold and aggregate in a similar way, following common aggregation steps. The process includes the formation of dimers, trimers, and low molecular weight prefibrillar oligomers, characterized by the typical morphology of globules less than 10 nm diameter. The globules spontaneously form linear or annular structures and, eventually, mature fibers. The rate of this process depends on characteristics intrinsic to the different proteins and to environmental conditions (i.e., pH, ionic strength, solvent composition, temperature). In the case of neurodegenerative diseases, it is now generally agreed that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. However, the molecular mechanism by which these oligomers trigger neuronal damage is still unclear. In particular, it is not clear if there is a peculiar structure at the basis of the neurotoxic effect and how this structure interacts with neurons. This review will focus on the results we obtained using salmon Calcitonin, an amyloid protein characterized by a very slow aggregation rate, which allowed us to closely monitor the aggregation process. We used it as a tool to investigate the characteristics of amyloid oligomers formation and their interactions with neuronal cells. Our results indicate that small globules of about 6 nm could be the responsible for the neurotoxic effects. Moreover, our data suggest that the rich content in lipid rafts of neuronal cell plasma membrane may render neurons particularly vulnerable to the amyloid protein toxic effect.

  9. Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid Bioadhesive Nanoparticles

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2014-01-01

    Full Text Available The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT. Therefore, poly(methyl vinyl ether maleic acid [P(MVEMA] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1, iv solution of sCT (5 μg·kg−1, and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly.

  10. Noncovalent pegylation by dansyl-poly(ethylene glycol)s as a new means against aggregation of salmon calcitonin.

    Science.gov (United States)

    Mueller, Claudia; Capelle, Martinus A H; Arvinte, Tudor; Seyrek, Emek; Borchard, Gerrit

    2011-05-01

    During all stages of protein drug development, aggregation is one of the most often encountered problems. Covalent conjugation of poly(ethylene glycol) (PEG), also called PEGylation, to proteins has been shown to reduce aggregation of proteins. In this paper, new excipients based on PEG are presented that are able to reduce aggregation of salmon calcitonin (sCT). Several PEG polymers consisting of a hydrophobic dansyl-headgroup attached to PEGs of different molecular weights have been synthesized and characterized physicochemically. After addition of dansyl-methoxypoly(ethylene glycol) (mPEG) 2 kDa to a 40 times molar excess of sCT resulted in an increase in dansyl-fluorescence and a decrease in 90° light scatter suggesting possible interactions. The aggregation of sCT in different buffer systems in presence or absence of the different dansyl-PEGs was measured by changes in Nile red fluorescence and turbidity. Dansyl-mPEG 2 kDa in a 1:1 molar ratio to sCT strongly reduced aggregation. Reduction of sCT aggregation was also measured for the bivalent dansyl-PEG 3 kDa in a 1:1 molar ratio. Dansyl-mPEG 5 kDa deteriorated sCT aggregation. Potential cytotoxicity and hemolysis were investigated. This paper shows that dansyl-PEGs are efficacious in reducing aggregation of sCT.

  11. The Slowly Aggregating Salmon Calcitonin: A Useful Tool for the Study of the Amyloid Oligomers Structure and Activity

    Directory of Open Access Journals (Sweden)

    Marco Diociaiuti

    2011-12-01

    Full Text Available Amyloid proteins of different aminoacidic composition share the tendency to misfold and aggregate in a similar way, following common aggregation steps. The process includes the formation of dimers, trimers, and low molecular weight prefibrillar oligomers, characterized by the typical morphology of globules less than 10 nm diameter. The globules spontaneously form linear or annular structures and, eventually, mature fibers. The rate of this process depends on characteristics intrinsic to the different proteins and to environmental conditions (i.e., pH, ionic strength, solvent composition, temperature. In the case of neurodegenerative diseases, it is now generally agreed that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. However, the molecular mechanism by which these oligomers trigger neuronal damage is still unclear. Inparticular, it is not clear if there is a peculiar structure at the basis of the neurotoxic effect and how this structure interacts with neurons. This review will focus on the results we obtained using salmon Calcitonin, an amyloid protein characterized by a very slow aggregation rate, which allowed us to closely monitor the aggregation process. We used it as a tool to investigate the characteristics of amyloid oligomers formation and their interactions with neuronal cells. Our results indicate that small globules of about 6 nm could be the responsible for the neurotoxic effects. Moreover, our data suggest that the rich content in lipid rafts of neuronal cell plasma membrane may render neurons particularly vulnerable to the amyloid protein toxic effect.

  12. Calcitonin gene-related peptide regulation of glial cell-line derived neurotrophic factor in differentiated rat myotubes.

    Science.gov (United States)

    Rosa, Elyse; Cha, Jieun; Bain, James R; Fahnestock, Margaret

    2015-03-01

    Glial cell-line derived neurotrophic factor (GDNF) is the most potent trophic factor for motoneuron survival and neuromuscular junction formation. GDNF is upregulated in injured or denervated skeletal muscle and returns to normal levels following reinnervation. However, the mechanism by which GDNF is regulated in denervated muscle is not well understood. The nerve-derived neurotransmitter calcitonin gene-related peptide (CGRP) is upregulated following neuromuscular injury and is subsequently released from motoneurons at the neuromuscular junction. CGRP also promotes nerve regeneration, but the mechanism is not well understood. The current study investigates whether this increase in CGRP regulates GDNF, thus playing a key role in promoting regeneration of injured nerves. This study demonstrates that CGRP increases GDNF secretion without affecting its transcription or translation. Rat L6 myoblasts were differentiated into myotubes and subsequently treated with CGRP. GDNF mRNA expression levels were quantified by quantitative real-time reverse transcription-polymerase chain reaction, and secreted GDNF was quantified in the conditioned medium by ELISA. CGRP treatment increased secreted GDNF protein without altering GDNF mRNA levels. The translational inhibitor cycloheximide did not affect CGRP-induced GDNF secreted protein levels, whereas the secretional inhibitor brefeldin A blocked the CGRP-induced increase in GDNF. This study highlights the importance of injury-induced upregulation of CGRP by exposing its ability to increase GDNF levels and demonstrates a secretional mechanism for regulation of this key regeneration-promoting neurotrophic factor.

  13. Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons.

    Science.gov (United States)

    Bucelli, Robert C; Gonsiorek, Eugene A; Kim, Woo-Yang; Bruun, Donald; Rabin, Richard A; Higgins, Dennis; Lein, Pamela J

    2008-03-01

    Clinical and experimental observations suggest that statins may be useful for treating diseases presenting with predominant neurogenic inflammation, but the mechanism(s) mediating this potential therapeutic effect are poorly understood. In this study, we tested the hypothesis that statins act directly on sensory neurons to decrease expression of proinflammatory neuropeptides that trigger neurogenic inflammation, specifically calcitonin gene-related peptide (CGRP) and substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay, and immunocytochemistry were used to quantify CGRP and substance P expression in dorsal root ganglia (DRG) harvested from adult male rats and in primary cultures of sensory neurons derived from embryonic rat DRG. Systemic administration of statins at pharmacologically relevant doses significantly reduced CGRP and substance P levels in DRG in vivo. In cultured sensory neurons, statins blocked bone morphogenetic protein (BMP)-induced CGRP and substance P expression and decreased expression of these neuropeptides in sensory neurons pretreated with BMPs. These effects were concentration-dependent and occurred independent of effects on cell survival or axon growth. Statin inhibition of neuropeptide expression was reversed by supplementation with mevalonate and cholesterol, but not isoprenoid precursors. BMPs signal via Smad activation, and cholesterol depletion by statins inhibited Smad1 phosphorylation and nuclear translocation. These findings identify a novel action of statins involving down-regulation of proinflammatory neuropeptide expression in sensory ganglia via cholesterol depletion and decreased Smad1 activation and suggest that statins may be effective in attenuating neurogenic inflammation.

  14. Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction.

    Science.gov (United States)

    Pang, Pai; Shimo, Tsuyoshi; Takada, Hiroyuki; Matsumoto, Kenichi; Yoshioka, Norie; Ibaragi, Soichiro; Sasaki, Akira

    2015-11-06

    Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.

  15. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers.

    Science.gov (United States)

    Kruuse, C; Iversen, H K; Jansen-Olesen, I; Edvinsson, L; Olesen, J

    2010-04-01

    The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 µg kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 ± 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.

  16. Immature osteoblastic MG63 cells possess two calcitonin gene-related peptide receptor subtypes that respond differently to [Cys(Acm)(2,7)] calcitonin gene-related peptide and CGRP(8-37).

    Science.gov (United States)

    Kawase, Tomoyuki; Okuda, Kazuhiro; Burns, Douglas M

    2005-10-01

    Calcitonin gene-related peptide (CGRP) is clearly an anabolic factor in skeletal tissue, but the distribution of CGRP receptor (CGRPR) subtypes in osteoblastic cells is poorly understood. We previously demonstrated that the CGRPR expressed in osteoblastic MG63 cells does not match exactly the known characteristics of the classic subtype 1 receptor (CGRPR1). The aim of the present study was to further characterize the MG63 CGRPR using a selective agonist of the putative CGRPR2, [Cys(Acm)(2,7)]CGRP, and a relatively specific antagonist of CGRPR1, CGRP(8-37). [Cys(Acm)(2,7)]CGRP acted as a significant agonist only upon ERK dephosphorylation, whereas this analog effectively antagonized CGRP-induced cAMP production and phosphorylation of cAMP response element-binding protein (CREB) and p38 MAPK. Although it had no agonistic action when used alone, CGRP(8-37) potently blocked CGRP actions on cAMP, CREB, and p38 MAPK but had less of an effect on ERK. Schild plot analysis of the latter data revealed that the apparent pA2 value for ERK is clearly distinguishable from those of the other three plots as judged using the 95% confidence intervals. Additional assays using 3-isobutyl-1-methylxanthine or the PKA inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide hydrochloride (H-89) indicated that the cAMP-dependent pathway was predominantly responsible for CREB phosphorylation, partially involved in ERK dephosphorylation, and not involved in p38 MAPK phosphorylation. Considering previous data from Scatchard analysis of [125I]CGRP binding in connection with these results, these findings suggest that MG63 cells possess two functionally distinct CGRPR subtypes that show almost identical affinity for CGRP but different sensitivity to CGRP analogs: one is best characterized as a variation of CGRPR1, and the second may be a novel variant of CGRPR2.

  17. NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.

    Science.gov (United States)

    Rawat, Atul; Kumar, Dinesh

    2013-01-01

    Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(α) chemical shifts and three bond H(N) -H(α) coupling constants indicated that most of the residues of the peptide are populating the α-helical region of the Ramachandran (ϕ, ψ) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (10(2) -10(3)  s(-1) ), inferred by the multiple chemical shift assignments in the region Leu4-Leu12 and around Pro23 (for residues Gln20-Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self-association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The (15) N NMR-relaxation data revealed (i) the presence of slow (microsecond-to-millisecond) timescale dynamics in the N-terminal region (Cys1-Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond-to-picosecond) motions in the C-terminal arm. Put together, the various results suggested that (i) the flexible C-terminal of sCT (from Thr25-Thr31) is involved in identification of specific target receptors, (ii) whereas the N-terminal of sCT (from Cys1-Gln20) in solution - exhibiting significant amount of conformational plasticity and strong bias towards biologically active α-helical structure - facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs.

  18. 鲑鱼降钙素致不良反应的文献分析%A Literature Analysis of Adverse Drug Reactions Induced by Salmon Calcitonin

    Institute of Scientific and Technical Information of China (English)

    苏娜; 吴逢波; 徐珽

    2013-01-01

    Objective To study the characteristics and the general pattern of the adverse drug reaction (ADR) induced by salmon calcitonin. Methods ADR induced by salmon calcitonin reported in domestic medical journals during January 1994 to March 2012 were retrieved from CNKI and WanFang databases. Classification and statistical analysis were carried out according to patients' age, gender, route of administration, dosage, time of the occurrence of ADR, clinical symptoms, allergic history, treatment and recovery. Results Fifteen ADR cases involved the integumentary system , cardiovascular system, digestive system, nervous system and allergic reaction, with advanced age group and women showing the highest incidence. Conclusion Salmon calcitonin should be used with caution in the clinic for it may induce ADR.%目的 总结鲑鱼降钙素致不良反应的一般规律和特点.方法 检索中国期刊全文数据库(CNKI)、万方数据库(WanFang)1994年1月-2012年3月鲑鱼降钙素所致不良反应的个案报道,按患者年龄、性别、给药途径、用药剂量、不良反应发生时间、临床表现症状、有无过敏史、治疗与转归等进行分类统计分析.结果 15例不良反应包括皮肤系统、心血管系统、消化系统、神经系统和超敏反应,高年龄段和女性发生率较高.结论 临床上应重视鲑鱼降钙素可致不良反应,坚持合理用药.

  19. Role in diuresis of a calcitonin receptor (GPRCAL1 expressed in a distal-proximal gradient in renal organs of the mosquito Aedes aegypti (L..

    Directory of Open Access Journals (Sweden)

    Hyeogsun Kwon

    Full Text Available Evolution of anthropophilic hematophagy in insects resulted in the coordination of various physiological processes for survival. In female mosquitoes, a large blood meal provides proteins for egg production and as a trade-off, rapid elimination of the excess water and solutes (Na(+, Cl(- is critical for maintaining homeostasis and removing excess weight to resume flight and avoid predation. This post-prandial excretion is achieved by the concerted action of multiple hormones. Diuresis and natriuresis elicited by the calcitonin-like diuretic hormone 31 (DH(31 are believed to be mediated by a yet uncharacterized calcitonin receptor (GPRCAL in the mosquito Malpighian tubules (MTs, the renal organs. To contribute knowledge on endocrinology of mosquito diuresis we cloned GPRCAL1 from MT cDNA. This receptor is the ortholog of the DH(31 receptor from Drosophila melanogaster that is expressed in principal cells of the fruit fly MT. Immunofluorescence similarly showed AaegGPRCAL1 is present in MT principal cells in A. aegypti, however, exhibiting an overall gradient-like pattern along the tubule novel for a GPCR in insects. Variegated, cell-specific receptor expression revealed a subpopulation of otherwise phenotypically similar principal cells. To investigate the receptor contribution to fluid elimination, RNAi was followed by urine measurement assays. In vitro, MTs from females that underwent AaegGPRcal1 knock-down exhibited up to 57% decrease in the rate of fluid secretion in response to DH(31. Live females treated with AaegGPRcal1 dsRNA exhibited 30% reduction in fluid excreted after a blood meal. The RNAi-induced phenotype demonstrates the critical contribution of this single secretin-like family B GPCR to fluid excretion in invertebrates and highlights its relevance for the blood feeding adaptation. Our results with the mosquito AaegGPRCAL1 imply that the regulatory function of calcitonin-like receptors for ion and fluid transport in renal organs

  20. Role in diuresis of a calcitonin receptor (GPRCAL1) expressed in a distal-proximal gradient in renal organs of the mosquito Aedes aegypti (L.).

    Science.gov (United States)

    Kwon, Hyeogsun; Lu, Hsiao-Ling; Longnecker, Michael T; Pietrantonio, Patricia V

    2012-01-01

    Evolution of anthropophilic hematophagy in insects resulted in the coordination of various physiological processes for survival. In female mosquitoes, a large blood meal provides proteins for egg production and as a trade-off, rapid elimination of the excess water and solutes (Na(+), Cl(-)) is critical for maintaining homeostasis and removing excess weight to resume flight and avoid predation. This post-prandial excretion is achieved by the concerted action of multiple hormones. Diuresis and natriuresis elicited by the calcitonin-like diuretic hormone 31 (DH(31)) are believed to be mediated by a yet uncharacterized calcitonin receptor (GPRCAL) in the mosquito Malpighian tubules (MTs), the renal organs. To contribute knowledge on endocrinology of mosquito diuresis we cloned GPRCAL1 from MT cDNA. This receptor is the ortholog of the DH(31) receptor from Drosophila melanogaster that is expressed in principal cells of the fruit fly MT. Immunofluorescence similarly showed AaegGPRCAL1 is present in MT principal cells in A. aegypti, however, exhibiting an overall gradient-like pattern along the tubule novel for a GPCR in insects. Variegated, cell-specific receptor expression revealed a subpopulation of otherwise phenotypically similar principal cells. To investigate the receptor contribution to fluid elimination, RNAi was followed by urine measurement assays. In vitro, MTs from females that underwent AaegGPRcal1 knock-down exhibited up to 57% decrease in the rate of fluid secretion in response to DH(31). Live females treated with AaegGPRcal1 dsRNA exhibited 30% reduction in fluid excreted after a blood meal. The RNAi-induced phenotype demonstrates the critical contribution of this single secretin-like family B GPCR to fluid excretion in invertebrates and highlights its relevance for the blood feeding adaptation. Our results with the mosquito AaegGPRCAL1 imply that the regulatory function of calcitonin-like receptors for ion and fluid transport in renal organs arose early

  1. High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren; Schifter, S

    2001-01-01

    catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; padrenaline levels (r=-0.......001) and central circulation time (r=-0.49; padrenaline (-16%; p... to COMP(art) disappeared. The relation of COMP(art) to CGRP and circulatory variables remained unchanged. CONCLUSION: Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline...

  2. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

    DEFF Research Database (Denmark)

    Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders;

    2010-01-01

    pathophysiology. Here we study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS......Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine...

  3. High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S; Schifter, S;

    2001-01-01

    , vasoactivity was manipulated by inhalation of oxygen. STUDY POPULATION AND METHODS: In 20 patients with alcoholic cirrhosis and 12 controls we determined COMP(art) (stroke volume relative to pulse pressure), cardiac output, plasma volume, systemic vascular resistance, central circulation time, plasma...... catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; p

  4. Calcitonin gene-related peptide in medullary thyroid carcinomas: characterization of molecular forms including the amidated C-terminus.

    Science.gov (United States)

    Schifter, S; Johnsen, A H

    1994-01-01

    CGRP was extracted from three familial and four sporadic medullary thyroid carcinomas (MTC) and was measured by an assay specific for the amidated C-terminus. The antibody showed equal affinity for alpha- and beta-CGRP. All tumors contained high concentrations of CGRP (range: 63-7889 pmol/g) compared to spinal cord (86 pmol/g), thyroid gland (4 pmol/g), and two small-cell lung carcinomas (4 and 1 pmol/g, respectively). The concentration of calcitonin (CT) was determined with an assay specific for an epitope involving the midportion and C-terminal end of the molecule. In six of the seven tumors investigated, concentrations of CT were found to be higher than for CGRP. Gel chromatography showed heterogeneity with respect to CGRP immunoreactivity. Thus, in all seven extracts, three peaks were seen with Kd values 0.37, 0.63, and 0.80, respectively. This profile of immunoreactive CGRP was similar to that obtained from human medulla spinalis, thereby indicating normal posttranslational processing of pro-CGRP in MTC tumors. Further characterization of the three main peaks identified by gel chromatography was performed on pooled fractions from one of the tumors using HPLC, sequencing, and mass spectrometry. The immunoreactive peak with Kd 0.37 was identified as human beta-CGRP, the peak with Kd 0.63 as 19-37 beta-CGRP, and the peak with Kd 0.80 as 25-37 beta-CGRP. No alpha-CGRP was identified in this tumor. This indicates selective expression of beta-CGRP, at least in the tumor investigated.

  5. Tryptophan-mPEGs: novel excipients that stabilize salmon calcitonin against aggregation by non-covalent PEGylation.

    Science.gov (United States)

    Mueller, Claudia; Capelle, Martinus A H; Arvinte, Tudor; Seyrek, Emek; Borchard, Gerrit

    2011-11-01

    Protein aggregation, which is triggered by various factors, is still one of the most prevalent problems encountered during all stages of protein formulation development. In this publication, we present novel excipients, tryptophan-mPEGs (Trp-mPEGs) of 2 and 5 kDa molecular weight and suggest their use in protein formulation. The synthesis and physico-chemical characterization of the excipients are described. Possible cytotoxic and hemolytic activities of the Trp-mPEGs were examined. Turbidity, 90° static light scatter, intrinsic fluorescence, fluorescence after staining the samples with Nile Red and fluorescence microscopy were used to study the inhibitory effect of the Trp-mPEGs on the aggregation of salmon calcitonin (sCT) in different buffer systems and at various molar ratios. Aggregation of sCT was reduced significantly with increasing concentrations of Trp-mPEG 2 kDa. A 10-fold molar excess of Trp-mPEG 2 kDa suppressed almost completely the aggregation of sCT in 10mM sodium citrate buffer (pH 6) for up to 70 h. Trp-mPEG 5 kDa also reduced the aggregation of sCT, though less pronounced than Trp-mPEG 2 kDa. Low aggregation of sCT was measured after approximately 10 days in 10mM sodium citrate buffer, pH 5, with a 10-fold molar excess of Trp-mPEG 2 kDa. This paper shows that Trp-mPEGs are potent excipients in reducing the aggregation of sCT. Trp-mPEGs are superior to dansyl-PEGs concerning the stabilization of sCT in a harsh environment, wherein sCT is prone to aggregation. Trp-mPEGs might therefore also be used for stabilization of other biopharmaceuticals prone to aggregation.

  6. Structural determinants of salmon calcitonin bioactivity: the role of the Leu-based amphipathic alpha-helix.

    Science.gov (United States)

    Andreotti, Giuseppina; Méndez, Blanca López; Amodeo, Pietro; Morelli, Maria A Castiglione; Nakamuta, Hiromichi; Motta, Andrea

    2006-08-25

    Salmon calcitonin (sCT) forms an amphipathic helix in the region 9-19, with the C-terminal decapeptide interacting with the helix (Amodeo, P., Motta, A., Strazzullo, G., Castiglione Morelli, M. A. (1999) J. Biomol. NMR 13, 161-174). To uncover the structural requirements for the hormone bioactivity, we investigated several sCT analogs. They were designed so as to alter the length of the central helix by removal and/or replacement of flanking residues and by selectively mutating or deleting residues inside the helix. The helix content was assessed by circular dichroism and NMR spectroscopies; the receptor binding affinity in human breast cancer cell line T 47D and the in vivo hypocalcemic activity were also evaluated. In particular, by NMR spectroscopy and molecular dynamics calculations we studied Leu(23),Ala(24)-sCT in which Pro(23) and Arg(24) were replaced by helix inducing residues. Compared with sCT, it assumes a longer amphipathic alpha-helix, with decreased binding affinity and one-fifth of the hypocalcemic activity, therefore supporting the idea of a relationship between a definite helix length and bioactivity. From the analysis of other sCT mutants, we inferred that the correct helix length is located in the 9-19 region and requires long range interactions and the presence of specific regions of residues within the sequence for high binding affinity and hypocalcemic activity. Taken together, the structural and biological data identify well defined structural parameters of the helix for sCT bioactivity.

  7. The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping.

    Science.gov (United States)

    Braegger, Fiona E; Asarian, Lori; Dahl, Kirsten; Lutz, Thomas A; Boyle, Christina N

    2014-10-01

    Amylin reduces meal size by activating noradrenergic neurons in the area postrema (AP). Neurons in the AP also mediate the eating-inhibitory effects of salmon calcitonin (sCT), a potent amylin agonist, but the phenotypes of the neurons mediating its effect are unknown. Here we investigated whether sCT activates similar neuronal populations to amylin, and if its anorectic properties also depend on AP function. Male rats underwent AP lesion (APX) or sham surgery. Meal patterns were analysed under ad libitum and post-deprivation conditions. The importance of the AP in mediating the anorectic action of sCT was examined in feeding experiments of dose-response effects of sCT in APX vs. sham rats. The effect of sCT to induce Fos expression was compared between surgery groups, and relative to amylin. The phenotype of Fos-expressing neurons in the brainstem was examined by testing for the co-expression of dopamine beta hydroxylase (DBH) or tryptophan hydroxylase (TPH). By measuring the apposition of vesicular glutamate transporter-2 (VGLUT2)-positive boutons, potential glutamatergic input to amylin- and sCT-activated AP neurons was compared. Similar to amylin, an intact AP was necessary for sCT to reduce eating. Further, co-expression between Fos activation and DBH after amylin or sCT did not differ markedly, while co-localization of Fos and TPH was minor. Approximately 95% of neurons expressing Fos and DBH after amylin or sCT treatment were closely apposed to VGLUT2-positive boutons. Our study suggests that the hindbrain pathways engaged by amylin and sCT share many similarities, including the mediation by AP neurons.

  8. In vitro and in vivo characterisation of a novel peptide delivery system: amphiphilic polyelectrolyte-salmon calcitonin nanocomplexes.

    Science.gov (United States)

    Cheng, Woei-Ping; Thompson, Colin; Ryan, Sinéad M; Aguirre, Tanira; Tetley, Laurence; Brayden, David J

    2010-10-15

    The cationic peptide, salmon calcitonin (sCT) was complexed with the cationic amphiphilic polyelectrolyte, poly(allyl)amine, grafted with palmitoyl and quaternary ammonium moieties at pH 5.0 and 7.4 to yield particulates (sCT-QPa). The complexes were approximately 200 nm in diameter, had zeta potentials ranging from +20 to +50 mV, and had narrow polydispersity indices (PDIs). Differential scanning calorimetry revealed the presence of an interaction between sCT and QPa in the complexes. Electron microscopy confirmed the zeta-size data and revealed a vesicular bilayer structure with an aqueous core. Tyrosine- and Nile red fluorescence indicated that the complexes retained gross physical stability for up to 7 days, but that the pH 5.0 complexes were more stable. The complexes were more resistant to peptidases, serum and liver homogenates compared to free sCT. In vitro bioactivity was measured by cAMP production in T47D cells and the complexes had EC50 values in the nM range. While free sCT was unable to generate cAMP following storage for 7 days, the complexes retained approximately 33% activity. When the complexes were injected intravenously to rats, free and complexed sCT (pH 5.0 and 7.4) but not QPa reduced serum calcium over 120 min. Free and complexed sCT but not QPa also reduced serum calcium over 240 min following intra-jejunal administration. In conclusion, sCT-QPa nanocomplexes that have been synthesised are stable, bioactive and resistant to a range of peptidases. These enhanced features suggest that they may have the potential for improved efficacy when formulated for injected and oral delivery.

  9. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats.

    Science.gov (United States)

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V; Gydesen, Sofie; Ottosen, Ida; Henriksen, Jan Erik; Beck-Nielsen, Henning; Christiansen, Claus; Karsdal, Morten A; Henriksen, Kim

    2014-08-15

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma glucoregulatory hormones and pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced anorectic action during the 7 days lead-in period and markedly reduced food intake and body weight in conjunction with improved glucose homeostasis. During the maintenance period, oral sCT normalized food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes.

  10. Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines.

    Science.gov (United States)

    Messier, A A; Heyder, E; Braithwaite, W R; McCluggage, C; Peck, A; Schaefer, K E

    1979-01-01

    Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

  11. The association of single nucleotide polymorphisms in the calcitonin gene with primary osteoarthritis of the knee in Mexican mestizo population.

    Science.gov (United States)

    Magaña, J J; Muñoz, B; Borgonio-Cuadra, V M; Razo-Estrada, C; González-Huerta, C; Cortés-González, S; Albores, A; Miranda-Duarte, A

    2013-10-01

    Primary osteoarthritis (OA) is a multifactorial disorder with several genetics factors involved. Calcitonin (CT) has been suggested to possess chondroprotective effects and could play an important role in the pathogenesis of OA. The aim of this study was to investigate whether genetic variations in or adjacent to the CT gene may be associated with primary OA of the knee in Mexican mestizo population. We conducted a case-control study to investigate the association between six single nucleotide polymorphisms at the CT locus and OA of the knee in 107 cases and 106 controls. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee ≥ 2. Controls were subjects >40 years of age with a radiologic score <2. Non-conditional logistic regression was developed to evaluate risk magnitude. The G allele and GT genotype frequencies of the G-706T polymorphism and the C allele and CC genotype of the C-778T polymorphism were significantly higher in patients with OA than in control subjects. The GG genotype of the G-706T was associated with lower risk of the development of OA of the knee. According to the results, the G-706T and the C-778T polymorphisms were related to the Cdx1 and Mzf1 transcription factor binding sites, respectively. Therefore, these could be related to regulation sequences in the CT gene promoter. In conclusion, G-706T and C-778T polymorphisms in the CT gene are significantly associated with the development of primary OA of the knee.

  12. Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

    Directory of Open Access Journals (Sweden)

    Cady Ryan J

    2011-12-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP, a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD. Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.

  13. Effect of calcitonin gene-related peptide on the neurogenesis of rat adipose-derived stem cells in vitro.

    Directory of Open Access Journals (Sweden)

    Qin Yang

    Full Text Available Calcitonin gene-related peptide (CGRP promotes neuron recruitment and neurogenic activity. However, no evidence suggests that CGRP affects the ability of stem cells to differentiate toward neurogenesis. In this study, we genetically modified rat adipose-derived stem cells (ADSCs with the CGRP gene (CGRP-ADSCs and subsequently cultured in complete neural-induced medium. The formation of neurospheres, cellular morphology, and proliferative capacity of ADSCs were observed. In addition, the expression of the anti-apoptotic protein Bcl-2 and special markers of neural cells, such as Nestin, MAP2, RIP and GFAP, were evaluated using Western blot and immunocytochemistry analysis. The CGRP-ADSCs displayed a greater proliferation than un-transduced (ADSCs and Vector-transduced (Vector-ADSCs ADSCs (p<0.05, and lower rates of apoptosis, associated with the incremental expression of Bcl-2, were also observed for CGRP-ADSCs. Moreover, upon neural induction, CGRP-ADSCs formed markedly more and larger neurospheres and showed round cell bodies with more branching extensions contacted with neighboring cells widely. Furthermore, the expression levels of Nestin, MAP2, and RIP in CGRP-ADSCs were markedly increased, resulting in higher levels than the other groups (p<0.05; however, GFAP was distinctly undetectable until day 7, when slight GFAP expression was detected among all groups. Wnt signals, primarily Wnt 3a, Wnt 5a and β-catenin, regulate the neural differentiation of ADSCs, and CGRP gene expression apparently depends on canonical Wnt signals to promote the neurogenesis of ADSCs. Consequently, ADSCs genetically modified with CGRP exhibit stronger potential for differentiation and neurogenesis in vitro, potentially reflecting the usefulness of ADSCs as seed cells in therapeutic strategies for spinal cord injury.

  14. Coated minispheres of salmon calcitonin target rat intestinal regions to achieve systemic bioavailability: Comparison between intestinal instillation and oral gavage.

    Science.gov (United States)

    Aguirre, Tanira A S; Aversa, Vincenzo; Rosa, Mónica; Guterres, Sílvia S; Pohlmann, Adriana R; Coulter, Ivan; Brayden, David J

    2016-09-28

    Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45μmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations.

  15. Research Progress of Calcitonin as Treatment for Osteoporosis%降钙素治疗骨质疏松症的研究进展

    Institute of Scientific and Technical Information of China (English)

    连建强

    2011-01-01

    Osteoporosis treatment is mainly drug therapy,which can be preliminariely categorized into three major series of inhibiting bone absorption, promoting bone formation, and promoting bone calcification.Calcitonin treatment of osteoporosis effect, usage and dosage, and the combined use of other drugs are reviewed here, with the focus of the promoting fracture healing, elminiating pain function of calcitonin besides the inhibition of bone loss.%骨质疏松症的治疗主要以药物治疗为主,该类药物初步可分为抑制骨吸收、促进骨形成、促进骨钙化三大系列.现就降钙素(抑制骨吸收药)对骨质疏松症的治疗作用、用法、用量以及与其他类药物联合应用进行综述,重点阐述降钙素不仅可抑制骨丢失,还可促进骨折愈合、消除骨痛.

  16. The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Increases Insulin Sensitivity and Induces Weight Loss in Rats with Obesity

    DEFF Research Database (Denmark)

    Hjuler, Sara Toftegaard; Gydesen, Sofie; Andreassen, Kim Vietz

    2016-01-01

    Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s.c. ad...... combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance....... a sustained weight loss of up to 20% without any significant weight reduction in the pair-fed groups. Decreases in adipose tissues and lipid deposition in the liver were observed, while plasma adiponectin was increased and plasma leptin levels were decreased. Acute administration of KBP-042 led to impaired......Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s...

  17. Developmental localization of calcitonin gene-related peptide in dorsal sensory axons and ventral motor neurons of mouse cervical spinal cord.

    Science.gov (United States)

    Kim, Jeongtae; Sunagawa, Masanobu; Kobayashi, Shiori; Shin, Taekyun; Takayama, Chitoshi

    2016-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide, synthesized by alternative splicing of calcitonin gene mRNA. CGRP is characteristically distributed in the nervous system, and its function varies depending on where it is expressed. To reveal developmental formation of the CGRP network and its function in neuronal maturation, we examined the immunohistochemical localization of CGRP in the developing mouse cervical spinal cord and dorsal root ganglion. CGRP immunolabeling (IL) was first detected in motor neurons on E13, and in ascending axons of the posterior funiculus and DRG neurons on E14. CGRP-positive sensory axon fibers entered Laminae I and II on E16, and Laminae I through IV on E18. The intensity of the CGRP-IL gradually increased in both ventral and dorsal horns during embryonic development, but markedly decreased in the ventral horn after birth. These results suggest that CGRP is expressed several days after neuronal settling and entry of sensory fibers, and that the CGRP network is formed in chronological and sequential order. Furthermore, because CGRP is markedly expressed in motor neurons when axons are vastly extending and innervating targets, CGRP may also be involved in axonal elongation and synapse formation during normal development.

  18. Summary and Analysis of Adverse Drug Reactions Induced by Salmon Calcitonin for Injection%注射用鲑鱼降钙素不良反应汇总分析

    Institute of Scientific and Technical Information of China (English)

    苏娜; 吴斌; 徐?

    2013-01-01

    Objective To study the characteristics and the general pattern of adverse drug reactions ( ADR ) induced by salmon calcitonin. Methods The literatures of ADR induced by salmon calcitonin reported in the domestic medical journals during 1994-2012 were retrieved by means of CNKI,and a related database was established for statistical analysis. Results 15 cases of ADR induced by salmon calcitonin were retrieved,which including the integumentary system,cardiovascular system,digestive system,nervous system and allergic reaction. The advanced age group and women showed the higher incidence rate. Conclusion The adverse reactions caused by salmon calcitonin should arouse clinical attention to persist its rational use.%目的 探讨鲑鱼降钙素致不良反应的一般规律和特点.方法 检索(CNKI)1994年至2012年鲑鱼降钙素所致不良反应文献,并进行统计分析.结果 共检索到不良反应病例15例,包括皮肤系统、心血管系统、消化系统、神经系统和变态反应.在高年龄段和女性患者中发生率较高.结论 临床上应重视鲑鱼降钙素的不良反应,坚持合理用药.

  19. Pluronic F68 enhanced the conformational stability of salmon calcitonin in both aqueous solution and lyophilized solid form.

    Science.gov (United States)

    Lee, Ting-Huei; Lin, Shan-Yang

    2011-11-01

    The effects of different surfactants on the conformational stability and structural similarity of salmon calcitonin (sCT) in aqueous solution and lyophilized forms were investigated by using microscopic Fourier transform infrared (FTIR) spectroscopy with second-derivative spectral analysis. Six surfactants, HCO-60, sodium dodecyl sulfate (SDS), Tween 80, PEG 400, Pluronic 68, and F127 were selected. The sCT aqueous solution with or without different surfactants was, respectively, incubated at 40°C for up to 35 h. sCT films were casted on the CaF(2) plates and IR spectra were collected as a function of incubation time. Second derivative analysis showed that the native sCT having a major α-helical structure was gradually changed to the combination of α-helix, random coil, and β-sheet conformations in aqueous solution at 40°C. Similar conformational changes with delayed β-sheet formation were obtained for sCT after co-incubation with all the surfactants except Pluronic F68. When the native sCT was freeze-dried alone, a marked conformational alteration was found as illustrated by a poor spectral correlation coefficient (r) value of 0.823 as compared to that of the unlyophilized native sCT. This r value was significantly deviated from 1, strongly indicating the influence of lyophilization stress on the surfactant-free sCT. The r value for sCT after lyophilizing with HCO-60, Pluronic F127, PEG 400, or Pluronic F68 was >0.9, suggesting the possible stabilization of these surfactants in the lyophilization process. The sCT sample after lyophilizing with Pluronic F68 showed a highest r value (>0.968), indicating the most optimal stabilization effect of Pluronic F68 for sCT sample via lyophilization. Pluronic F68 was found to be the preferential surfactant for preventing the secondary structure changes in aqueous solution at 40°C as well as in lyophilized powder.

  20. Effects of salmon calcitonin on postmenopausal osteoporosis%鲑鱼降钙素治疗绝经后骨质疏松症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    熊萍; 董刚强; 李世云; 林勇; 饶进; 杜春; 苟晓琴; 李龙英

    2012-01-01

    目的 观察鲑鱼降钙素和凯思立D治疗绝经后骨质疏松症的疗效.方法 将128例绝经后骨质疏松症患者随机分为对照组和治疗组各64例,对照组口服凯思立D,1片/d;治疗组则在此基础上加用鲑鱼降钙素肌肉注射,50IU/次,1次/周,两组疗程均为6个月.治疗结束后,比较两组患者的疗效及不良反应情况.结果 治疗组总有效率为92.2%,明显高于对照组53.1%,差异有统计学意义(P<0.05);治疗组的骨密度较治疗前明显提高(P<0.05),而对照组的骨密度则无明显变化,差异无统计学意义(P>0.5).结论 鲑鱼降钙素联合凯思立D治疗绝经后骨质疏松症疗效好,可明显改善症状,增加骨密度.%Objective To evaluate the effect of salmon calcitonin on postmenopausal osteoporosis patients. Methods 128 cases of postmenopausal osteoporosis were randomly divided into treatment group (n = 64) and the control group (n = 64). The cases in control group were given orally Kaisili D, 1 slice per day. On this basis,the treatment group were intramuscularly injected salmon calcitonin 50IU once a week for 6 months continuously. Results The total efficacy was 92. 2% in treatment group higher than that of control group. Bone mineral density (BMD) in treatment group increased significantly after treatments(P0. 05). Conclusion Salmon calcitonin combined with Kaisili D in treatment of postmenopausal osteoporosis has a good effect, can obviously improve symptoms and increase the bone density.

  1. Expression of a chimeric human/salmon calcitonin gene integrated into the Saccharomyces cerevisiae genome using rDNA sequences as recombination sites.

    Science.gov (United States)

    Sun, Hengyi; Zang, Xiaonan; Liu, Yuantao; Cao, Xiaofei; Wu, Fei; Huang, Xiaoyun; Jiang, Minjie; Zhang, Xuecheng

    2015-12-01

    Calcitonin participates in controlling homeostasis of calcium and phosphorus and plays an important role in bone metabolism. The aim of this study was to endow an industrial strain of Saccharomyces cerevisiae with the ability to express chimeric human/salmon calcitonin (hsCT) without the use of antibiotics. To do so, a homologous recombination plasmid pUC18-rDNA2-ura3-P pgk -5hsCT-rDNA1 was constructed, which contains two segments of ribosomal DNA of 1.1 kb (rDNA1) and 1.4 kb (rDNA2), to integrate the heterologous gene into host rDNA. A DNA fragment containing five copies of a chimeric human/salmon calcitonin gene (5hsCT) under the control of the promoter for phosphoglycerate kinase (P pgk ) was constructed to express 5hsCT in S. cerevisiae using ura3 as a selectable auxotrophic marker gene. After digestion by restriction endonuclease HpaI, a linear fragment, rDNA2-ura3-P pgk -5hsCT-rDNA1, was obtained and transformed into the △ura3 mutant of S. cerevisiae by the lithium acetate method. The ura3-P pgk -5hsCT sequence was introduced into the genome at rDNA sites by homologous recombination, and the recombinant strain YS-5hsCT was obtained. Southern blot analysis revealed that the 5hsCT had been integrated successfully into the genome of S. cerevisiae. The results of Western blot and ELISA confirmed that the 5hsCT protein had been expressed in the recombinant strain YS-5hsCT. The expression level reached 2.04 % of total proteins. S. cerevisiae YS-5hsCT decreased serum calcium in mice by oral administration and even 0.01 g lyophilized S. cerevisiae YS-5hsCT/kg decreased serum calcium by 0.498 mM. This work has produced a commercial yeast strain potentially useful for the treatment of osteoporosis.

  2. The calcitonin receptor gene is a candidate for regulation of susceptibility to herpes simplex type 1 neuronal infection leading to encephalitis in rat.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a fatal infection of the central nervous system (CNS predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL, Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5 governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.

  3. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine

    DEFF Research Database (Denmark)

    Dodick, David W; Goadsby, Peter J; Silberstein, Stephen D

    2014-01-01

    to treatment allocation during the study. The primary objective was to assess safety at 12 weeks after infusion. The primary efficacy endpoint was the change from baseline to weeks 5-8 in the frequency of migraine days, as recorded in patient electronic diaries. Patients were followed up until 24 weeks...... and one had one serious adverse event, and in the placebo group, one patient had one serious adverse event. There were no differences in vital signs or laboratory safety data between the two treatment groups. The mean change in migraine days between baseline and weeks 5-8 was -5·6 (SD 3·0) for the ALD403......BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo...

  4. Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Le, Han

    2009-01-01

    The involvement of calcitonin gene-related peptide (CGRP) in migraine pathophysiological mechanisms is shown by the facts that CGRP can induce migraine and that two CGRP antagonists, olcegepant and telcagepant, are effective in the treatment of migraine attacks. Increase of the neuropeptide CGRP...... during migraine and cluster headache attacks in the extracerebral circulation as measured in the external jugular vein (EJV) has been regarded as an established fact. Then in 2005, a study, using the migraine patients as their own controls, showed; however, no changes of CGRP in EJV. For migraine...... there is thus some uncertainty as to whether CGRP is increased in all migraine patients and more research is needed. In contrast, there are three 'positive' studies in cluster headache in which both sumatriptan, O(2) and spontaneous resolution normalized CGRP. The source of an increase of CGRP in EJV is most...

  5. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy.......Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...

  6. Effect of Chinese Herbal Fumigation Combined with Tuina on Vertigo and Concentrations of Endothelin and Calcitonin Gene-related Peptide in Patients with Vertebral Artery Cervical Spondylosis

    Institute of Scientific and Technical Information of China (English)

    Zhao Cheng-fei; Liu Xiao-an; Ding Yun

    2014-01-01

    Objective:To observe the effect of Chinese herbal fumigation combined with three-step tuina manipulation on concentration of endothelin (ET) and calcitonin gene-related peptide (CGRP) and vertigo in patients with vertebral artery cervical spondylosis (VACS). Methods:A total of 120 eligible cases were randomly allocated into an observation group and a control group, 60 in each group. Cases in the observation group were treated with Chinese herbal fumigation combined with three-step tuina manipulation, whereas cases in the control group were treated with oral Flunarizine Hydrochloride Capsules. Results: After treatment, vertigo in both groups was alleviated; there were intra-group significant differences in ET decrease and CGRP increase (P Conclusion: Chinese herbal fumigation combined with three-step tuina manipulation can regulate the levels of ET and CGRP and improve vertigo in patients with VACS. Its therapeutic efficacy is superior to oral Flunarizine Hydrochloride Capsules.

  7. Expression of calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in differing physiological states and following misoprostol administration.

    Science.gov (United States)

    Goharkhay, Nina; Lu, Jing; Felix, Juan C; Wing, Deborah A

    2007-09-01

    Our objective was to assess relative expression levels of mRNA for calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in various physiological states. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed myometrial samples from 46 women (10 menopausal, 10 nongravid premenopausal, 19 gravidae, and 7 premenopausal misoprostol-treated nongravid women) for the specific expression of CGRP-RCP mRNA. The expression of CGRP-RCP was significantly increased in gravid compared with nongravid myometrium ( P RCP expression were found among the other study groups. We concluded that the increased mRNA expression CGRP-RCP in gravid myometrium supports the possibility of involvement of CGRP in the control of myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of CGRP and CGRP-RCP in human myometrium.

  8. Do sensory calcitonin gene-related peptide nerve fibres in the rat pelvic plexus supply autonomic neurons projecting to the uterus and cervix?

    Science.gov (United States)

    Houdeau, E; Barranger, E; Rossano, B

    2002-10-25

    Sensory nerve fibres containing calcitonin gene-related peptide (CGRP) innervate neurons of the paracervical ganglion (PCG) in the female rat pelvic plexus. We have combined retrograde tracing with immunocytochemistry to investigate whether CGRP-immunoreactive (-IR) fibres supply neurons targeting the genital tract. Of the total neurons projecting to either the uterine horns or the cervix, 38 and 41% received CGRP-IR innervation, respectively. All these neurons displayed choline acetyltransferase-IR, thus are cholinergic. They were found throughout the PCG and other pelvic plexus ganglia, namely accessory ganglia (AG) and hypogastric plexus (HP). Pelvic nerve section showed that afferent fibres in these nerves provided most of the CGRP-IR fibres supplying uterine- or cervical-related neurons in the PCG/AG, none in HP. It is suggested that such sensory-motor network may provide a local pathway for reflex control of genital tract activity, acting through cholinergic nerve projections.

  9. Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2011-01-01

    was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal...... to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal...... trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level...

  10. Conjugation of salmon calcitonin to a combed-shaped end functionalized poly(poly(ethylene glycol) methyl ether methacrylate) yields a bioactive stable conjugate.

    Science.gov (United States)

    Ryan, Sinéad M; Wang, Xuexuan; Mantovani, Guiseppe; Sayers, Claire T; Haddleton, David M; Brayden, David J

    2009-04-02

    Salmon calcitonin (sCT) was conjugated via its N-terminal cysteine to a comb-shaped end-functionalized poly(poly(ethylene glycol) methyl ether methacrylate) (PolyPEG, 6.5 kDa), and to linear PEG (5 kDa). Conjugate molecular weight and purity was assessed by SEC-HPLC and MALDI-TOF MS. Bioactivity of conjugates was measured by cyclic AMP assay in T47D cells. Calcium and calcitonin levels were measured in rats following intravenous injections. Stability of conjugates was tested against serine proteases, intestinal and liver homogenates and serum. Cytotoxicity of conjugates was assessed by lactate dehydrogenase (LDH) assay and by haemolytic assay of rat red blood cells. Results showed that the two conjugates were of high purity with molecular weights similar to predictions. Both conjugates retained more than 85% bioactivity in vitro and had nanomolar EC(50) values similar to sCT. While both sCT-PolyPEG(6.5 K) and sCT-PEG(5 K) were resistant to metabolism by serine proteases, homogenates and serum, PolyPEG (6.5 K) was more so. Although both conjugates reduced serum calcium to levels similar to those achieved with sCT, PolyPEG(6.5 K) extended the T(1/2) and AUC of serum sCT over values achieved with sCT-PEG and sCT itself. None of PolyPEG, PEG or methacrylic acid displayed significant cytotoxicity. PolyPEG may therefore have potential to improve pharmacokinetic profiles of injected peptides.

  11. Calcitonin blood test

    Science.gov (United States)

    ... skin is broken) References Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. ...

  12. 不同产家鲑鱼降钙素治疗绝经后骨质疏松症的疗效与经济比较%Thecurativeeffectandtheeconomiccomparisonofdifferentproducers of salmon calcitonin in the treatment of patients with postmenopausal osteoporosis

    Institute of Scientific and Technical Information of China (English)

    赖习科

    2013-01-01

    Objective To compare the curative effect and economy of domestic and imported salmon calcitonin injection in the treatment of patients with postmenopausal osteoporosis. Methods 60 cases of postmenopausal osteoporosis were randomly divided into two groups,the control group were given imported salmon calcitonin injection treatment,while the observation group were given domestic salmon calcitonin injection treatment. Results There was no significant difference in the clinical effect and the bone density of patients with postmenopausal osteoporosis between the two groups(P>0.05).The price of domestic salmon calcitonin injection was lower than that of the import of salmon calcitonin injection. Conclusion Domestic salmon calcitonin injection combined with caltrate with vitamin D300 chewing tablets in the treatment of postmenopausal osteoporosis patients curative effect is reliable,and economical and practical.%目的比较国产与进口鲑鱼降钙素注射液治疗绝经后骨质疏松症的疗效与经济。方法60例绝经后骨质疏松症患者,分成观察组与对照组。对照组采用进口鲑鱼降钙素注射液治疗;观察组采用国产鲑鱼降钙素注射液治疗。结果两组疗效及绝经后骨质疏松症患者骨密度比较,差异均无统计学意义(P>0.05)。国产鲑鱼降钙素注射液价格低于进口鲑鱼降钙素注射液。结论国产鲑鱼降钙素注射液联合钙尔奇D300咀嚼片治疗绝经后骨质疏松症患者疗效可靠,而且经济实惠。

  13. A randomized double-blind placebo-controlled trial to investigate the effects of nasal calcitonin on bone microarchitecture measured by high-resolution peripheral quantitative computerized tomography in postmenopausal women — Study protocol

    Directory of Open Access Journals (Sweden)

    Azria Moise

    2008-04-01

    Full Text Available Abstract Background Bone microarchitecture is a significant determinant of bone strength. So far, the assessment of bone microarchitecture has required bone biopsies, limiting its utilization in clinical practice to one single skeletal site. With the advance of high-resolution imaging techniques, non-invasive in vivo measurement of bone microarchitecture has recently become possible. This provides an opportunity to efficiently assess the effects of anti-osteoporotic therapies on bone microarchitecture. We therefore designed a protocol to investigate the effects of nasal salmon calcitonin, an inhibitor of osteoclast activity, on bone microarchitecture in postmenopausal women, comparing weight bearing and non-weight bearing skeletal sites. Methods One hundred postmenopausal women will be included in a randomized, placebo-controlled, double-blind trial comparing the effect of nasal salmon calcitonin (200 UI/day to placebo over two years. Bone microarchitecture at the distal radius and distal tibia will be determined yearly by high-resolution peripheral quantitative computerized tomography (p-QCT with a voxel size of 82 μm and an irradiation of less than 5 μSv. Serum markers of bone resorption and bone formation will be measured every 6 months. Safety and compliance will be assessed. Primary endpoint is the change in bone microarchitecture; secondary endpoint is the change in markers of bone turnover. Hypothesis The present study should provide new information on the mode of action of nasal calcitonin. We hypothezise that - compared to placebo - calcitonin impacts on microstructural parameters, with a possible difference between weight bearing and non-weight bearing bones. Trial Registration ClinicalTrials.gov NCT00372099

  14. Clinical observation on treating vertebral compression fractures by magnetic therapy plus salmon calcitonin%磁疗法配合鲑降钙素治疗腰椎压缩性骨折的临床疗效

    Institute of Scientific and Technical Information of China (English)

    甘春正

    2015-01-01

    目的:探讨磁疗法配合鲑降钙素治疗腰椎压缩性骨折的临床疗效。方法:选取我院骨科门诊2013年4月-2014年2月收治的腰椎压缩性骨折患者100例,均采用磁疗法配合鲑降钙素治疗,并对其疗效进行观察和分析。结果:接受磁疗法配合鲑降钙素治疗的100例患者治疗15d,89例痊愈,11例好转,有效率为100%。因此采用磁疗法配合鲑降钙素治疗腰椎压缩性骨折,疗效显著,患者安全有效、易推广,与手术相比,避免了由于手术带来的风险及并发症,减轻患者的痛苦和负担,值得在临床推广应用。%Objective: To discuss clinical effects of magnetic therapy plus salmon calcitonin on vertebral compression fractures. Methods: 100 patients were given magnetic therapy plus salmon calcitonin, and clinical effects were observed and analyzed. Results: After 15 days of treatment, in 100 patients, 89 cases were cured, 11 cases were improved, the efficiency was 100%. Clinical efficacy of magnetic therapy plus salmon calcitonin was confirmed and safe. Compared with operation, magnetic therapy plus salmon calcitonin could avoid the risks and complications, reduce patient pain and burden, and were worthy of clinical application.

  15. Negative pressure for diabetic foot:Evaluation based on calcitonin gene-related peptide in the limb skin of dogs

    Institute of Scientific and Technical Information of China (English)

    Rui Ling; Jun Yi; Ling Wang; Mofan Ning

    2006-01-01

    BACKGROUND: Very good therapeutic effect has been obtained for limb negative pressure in treating limb ischemic diseases.But its mechanism in treating diabetic foot needs further investigation.OBJECTIVE:To observe the changes of calcitonin gene related peptide(CGRP)in sensory nerve fiber of skin of dogs with diabetic foot before and after limb negative pressure treatment,and make a comparison with normal dogs,then analyze the mechanism of limb negative pressure in treating diabetic foot.DESIGN:A randomized controlled animal experiment.SETTING:Third Department of General Surgery,Xijing Hospital,Fourth Military Medical University of Chinese PLA.MATERIALS:Fifteen healthy hybrid dogs,of either gender,weighing 12-18 kg,were provided by Animal Room,Xijing Hospital of the Fourth Military Medical University of Chinese PLA.After being numbered,the involved dogs were randomly assigned into 3 groups:treatment group,model group and normal control group,5 dogs each.Limb negative pressure therapeutic machine(self-made);Anti-CGRP serum (primary antibody,Watpa Company,England);rabbit anti-BigG(second antibody),ABC compound solution,DAB reagent,glucose oxidase reagent,Tdxon-X100 solution(Sigma company,USA),ammonium nickelous sulfate reagent(Xi'an Chemical Reagent Factory),neutral gum-solution(import,Shanghai Reagent Co.,Ltd.);Leitz1400 sliding freezing microtome(Leitz Company,Germany);Leica 1800 cryostat microtome(Leica Company,Germany);Quantimet570 image analyzer(Leica Company,Germany).METHODS:This experiment was carried out in the Animal Room,Xijing Hospital,Fourth Military Medical University of Chinese PLA from October 2005 to June 2006.①After the dogs in the treatment and model groups were anesthetized,their pancreatic tissues were removed completely and animal models of type I diabetes mellitus were developed.All the femoral artery branches including deep femoral artery were ligated and cut off.A helical wire was inserted into the distal femoral artery cavity for narrowing

  16. 鲑降钙素治疗髋部骨折的系统评价%Evaluation of salmon calcitonin in the treatment of hip fractures

    Institute of Scientific and Technical Information of China (English)

    程静; 晁爱军

    2015-01-01

    Objective To determine the efficacy of salmon calcitonin in the treatment of hip fractures.Methods The randomized clinical trials (RCTs) of salmon calcitonin treatment for hip fractures were searched from the CNKI (1994-2014.5), CBM (1978 -2014.5), VIP (989 -2014.5), Wanfang Data (1997 -2014.5), PubMed (1966-2014.5), Cochrane library (issue 2, 2014), and Embase (1990-2014.5).Data were extracted and Meta analysis was performed according to the Cochrane methods using RevMan 5.2.0 software.Results Eleven RCTs including 823 patients were eligible.Meta analysis showed that salmon calcitonin reduced the refracture rate in hip fracture patients [RR=0.41, 95% CI (0.04, 0.47)], relieved the pain after hip fracture [SMD=2.27, .95%CI (1.08, 3.46), P=0.0002], but did not affect bone mineral density.Since the indexes of bone metabolic markers, and the function of hip joint and fracture healing were not suitable for Meta analysis, we only made descriptive analysis.Conclusion Salmon calcitonin can reduce the refracture rate and release the pain of hip fracture patients.It also improves the hip function and promotes fracture healing.Therefore, we recommend salmon calcitonin as a routine treatment for hip fracture.But the results still need more rigorous, scientific clinical trials to confirm.%目的:系统评价鲑降钙素对髋部骨折的疗效。方法计算机检索中国期刊全文数据库(1994-2014.5),中国生物医学文献数据库(1978-2014.5),中文科技期刊全文数据库(1989-2014.5),数字化期刊全文数据库(1997-2014.5),PubMed (1966-2014.5),Cochrane library(2014年第2期),EMBASE(1990-2014.5),收集鲑降钙素治疗髋部骨折的随机对照实验(RCT),依据Cochrane评价手册5.1.0评价文献质量,并提取有效数据进行Meta分析。结果纳入11个RCT,共823名患者。 Meta分析结果示:鲑降钙素可降低髋部骨折患者的再骨折率[RR=0.41,95%CI(0.04,0.47

  17. The Effect of Salmon Calcitonin in Metastatic Bone Pain-relieving%鲑鱼降钙素缓解骨转移瘤骨痛的疗效观察

    Institute of Scientific and Technical Information of China (English)

    冯进益; 芮钢

    2013-01-01

    Objective :To evaluate the ef icacy of salmon calcitonin in control ing pain related to bone metastasis in cancer patients. Methods :The experimental group (EG) were treated with painkil ers and salmon calcitonin while the control group (CG) were given painkil ers only. VAS scores of the two groups were recorded and analyzed. Results :The VAS of EG decreased mildly after being treated during 7 to 14 days, however, we did not find them reducing obviously until 28 days. Conclusions:The ef ect of salmon calcitonin in metastatic bone pain-relieving was not significant dif erence.%目的:观察鲑鱼降钙素(密盖息)治疗肿瘤晚期骨转移癌性疼痛的临床疗效。方法实验组予密钙息联合止痛药,阴性对照组单纯予止痛药。记录两组的 VAS评分并进行统计分析。结果实验组于7~14 d起VAS下降1~2分,观察至28 d,未见明显降低。结论鲑鱼降钙素对骨转移瘤骨痛,效果不明显。

  18. Efficacy of Salmon Calcitonin in Treatment of Senile Osteoporosis%鲑鱼降钙素用于老年骨质疏松的疗效观察

    Institute of Scientific and Technical Information of China (English)

    孙秀芹; 英吉林; 张晓梅; 周迎生

    2015-01-01

    OBJECTIVE:To evaluate the clinical efficacy of salmon calcitonin in treatment of senile osteoporosis. METHODS:125 cases of elderly patients with senile osteoporosis admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University from May 2011 to Nov.2013 were divided into observation group and control group, 63 cases in observation group were treated with salmon calcitonin combined with calcium, and 62 cases in control group only received calcium; the clinical efficacy and incidence of adverse reactions in two groups were observed. RESULTS:After treatment, patients'bone mineral density of observation group was ( 0.786 ±0.135 ) g/cm2 , significantly higher than that of control group ( 0.719 ±0.126 ) g/cm2;the BGP levels of observation group was (20.1 ±5.2) ng/ml, significantly better than that of control group ( 17.5 ±4.3 ) ng/ml, the difference was statistically significant ( P<0.05) .The relief degree and median time of bone pain symptom in observation group were better than that in control group, with statistically significant difference(P<0.05).There were no adverse reactions in two groups of patients.CONCLUSIONS: Salmon calcitonin in treatment of senile osteoporosis has a good clinical efficacy, which can effectively relieve the bone pain of patients, shorten the treatment time, and has no significant adverse reactions.It is worthy of clinical promotion.%目的:评价鲑鱼降钙素治疗老年骨质疏松的临床疗效。方法:选取2011年5月一2013年11月首都医科大学附属北京安贞医院收治的老年骨质疏松患者125例,按随机数字表法分为观察组和对照组,观察组患者63例,选用鲑鱼降钙素联合钙剂进行治疗;对照组患者62例,仅选用钙剂进行治疗,观察2组患者的疗效及不良反应发生情况。结果:治疗后,观察组患者腰椎骨密度为(0.786±0.135) g/cm2,明显优于对照组的(0.719±0.126) g/cm2,差异有统计学意义(P<0.05

  19. Calcitonin gene-related peptide (CGRP and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

    Directory of Open Access Journals (Sweden)

    Eftekhari Sajedeh

    2011-11-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP has a key role in migraine pathophysiology and is associated with activation of the trigeminovascular system. The trigeminal ganglion, storing CGRP and its receptor components, projects peripheral to the intracranial vasculature and central to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal trigeminal nucleus (STN and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR and receptor activity modifying protein 1 (RAMP1 - in human and rat STN and at the C1-level, using a set of newly well characterized antibodies. In addition, double-stainings with CGRP and myelin basic protein (MBP, myelin, synaptophysin (synaptic vesicles or IB4 (C-fibers in general were performed. Results In the STN, the highest density of CGRP immunoreactive fibers were found in a network around fiber bundles in the superficial laminae. CLR and RAMP1 expression were predominately found in fibers in the spinal trigeminal tract region, with some fibers spanning into the superficial laminae. Co-localization between CGRP and its receptor components was not noted. In C1, CGRP was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal microscopy. Conclusions This study demonstrates the detailed expression of CGRP and its receptor components within STN in the brainstem and in the spinal cord at C1

  20. Bone repair in rats treated with sodic diclofenac and calcitonin Reparo ósseo em ratos tratados com diclofenaco sódico e calcitonina

    Directory of Open Access Journals (Sweden)

    Maria Cristina Pita Sassioto

    2006-01-01

    Full Text Available PURPOSE: To investigate clinical and histologically the bone repair in treated animals with calcitonin and sodic diclofenac. METHODS: Ninety-six femoral defects were created in forty-eight animals distributed in four groups (n=24: either left untreated, treated with the sodic diclofenac or calcitonin or both. Follow-up was 7, 14 and 21 days. Histological sections stained by haematoxylin-eosin was observed under light microscopy (100X and quantitatively scored for their trabecular formation. The groups and subgroups were compared being used the Kruskall-Wallis test. RESULTS: Smaller trabecular formation was observed in the animals of the group II and larger trabecular formation in the animals of the group III. Was found significant differences in the comparison between all the groups (Kruskall-Wallis, p OBJETIVO: Investigar clínica e histologicamente o reparo ósseo em animais tratados com calcitonina e diclofenaco sódico. MÉTODOS: Foram criados 96 defeitos femorais, em 48 animais distribuídos em quatro grupos (n = 24: não tratados, tratados com diclofenaco sódico ou calcitonina ou ambos. O período de seguimento foi 7, 14 e 21 dias. As secções coradas por hematoxilina e eosina foram observadas sob microscopia óptica (100x e analisadas quantitativamente em relação à neoformação trabecular. Os grupos e subgrupos foram comparados utilizando-se o teste de Kruskall-Wallis. RESULTADOS: Foi observada menor formação de trabéculas ósseas nos animais do grupo II e maior formação de trabéculas ósseo nos animais do grupo III. Foram encontradas diferenças significantes na comparação entre todos os grupos (Kruskall-Wallis, p <0.05. CONCLUSÃO: Os dados obtidos sugerem que o reparo ósseo é um processo tempo-dependente, que pode ser retardado pelo diclofenaco e acelerado pela calcitonina, quando utilizados isoladamente. O uso associado de calcitonina e diclofenaco sódico não mostrou ser a melhor opção terapêutica no tratamento de

  1. Roles of calcitonin gene-related peptide family in pain and opioid tolerance%降钙素基因相关肽家族在疼痛和阿片耐受中的作用

    Institute of Scientific and Technical Information of China (English)

    刘芳薇; 洪炎国

    2013-01-01

    The calcitonin gene-related peptide (CGRP) family mainly includes CGRPt,CGRPβ,adrenomedullin,calcitonin and amylin.The members of CGRP family and their receptors are widely distributed in the central and peripheral nervous systems.Studies show that members of CGRP family such as CGRP and adrenomedullin play important roles in the transmission of nociceptive information.At spinal level,CGRP promotes the transmission of nociceptive information,spinal morphine tolerance,migraine,inflammatory pain and neuropathic pain.At superspinal level,CGRP suppresses the transmission of nociceptive information.Adrenomedullin is a pain-related neuropeptide which has recently been demonstrated.It facilitates the transmission of nociceptive information and is involved in the development and maintenance of opioid tolerance.The involvement of amylin and calcitonin in pain is not clear yet.%降钙素基因相关肽(calcitonin gene-related peptide,CGRP)家族成员主要包括CGRPα、CGRPβ、肾上腺髓质素(adrenomedullin,AM)、降钙素(calcitonin,CT)和胰淀粉样蛋白(amylin,AMY).CGRP家族成员及其受体广泛分布于哺乳动物中枢和外周神经系统.研究表明,CGRP、AM等CGRP家族成员在伤害性信息传递过程中具有重要作用.在脊髓水平,CGRP促进痛觉信息传递、脊髓阿片耐受、偏头痛、炎性痛和神经病理性痛;在脊髓以上水平,CGRP则抑制痛觉信息的传递.AM是近年来才证实的与疼痛感受有密切关系的神经多肽,在脊髓水平促进痛觉信息的传递,在阿片耐受形成和维持中亦有重要作用.AMY和CT与疼痛的关系尚不十分明确.

  2. Calcitonin gene-related peptide in anterior and posterior horns of spinal cord after brachial plexus injury

    Institute of Scientific and Technical Information of China (English)

    Longju Chen; Peijun Wang; Feng Li; Wutian Wu

    2007-01-01

    BACKGROUND: The changes of calcitonin gene-related peptide (CGRP) expression are closely associated with peripheral nerve injury, whereas it should be further investigated whether the damage of central nerve can lead to the changes of CGRP expression, and whether it is associated with the neural regeneration and repair.OBJECTIVE: To observe the changing law of CGRP expression in the anterior and posterior horns of spinal cord following brachial plexus injury.DESIGN: A randomized controlled trial.SETTINGS: Department of Anatomy, Yunyang Medical College; Department of Anatomy, Basic Medical College, Sun Yat-sen University.MATERIALS: Sixty-five adult male SD rats of clean degree, weighing 180 - 220 g, provided by the experimental animal center of the Basic Medical College, Sun Yat-sen University, were randomly divided into control group (n =5) and experimental group (n =60), and the latter was subdivided into three damage groups: avulsion of anterior root group (n =20), disjunction of posterior root group (n =20) and transection of spinal cord group (n =20). Diaminobenzidine (DAB) chromogen, rabbit anti-CGRP polyclonal antibody were the products of Sigma Company; Leica image analytical apparatus was produced by QUIN Company (Germany); Histotome by Sigma Company.METHODS: The experiments were carried out in the Department of Anatomy, Basic Medical College, Sun Yat-sen University from September 2004 to March 2005. Three kinds of models of brachial plexus injury were established: In the avulsion of anterior root group, right C7 anterior root was avulsed, and the distal nerve residual root was transected. In the disjunction of posterior root group, right C7 anterior root was avulsed and right C5 - T1 posterior horns were cut to block the sensory afferent pathway. In the transection of spinal cord group, right C7 anterior root was avulsed and C5-6 segments of right spinal cord were semi-transected to block the cortical descending pathway. In the control group, C5 - T1

  3. Identification in the human central nervous system, pituitary, and thyroid of a novel calcitonin gene-related peptide, and partial amino acid sequence in the spinal cord.

    Science.gov (United States)

    Petermann, J B; Born, W; Chang, J Y; Fischer, J A

    1987-01-15

    Two human genes encoding precursors for two calcitonin gene-related peptides (CGRP) I (or alpha) and II (or beta) have been identified (Steenbergh, P. H., Höppener, J. W. M., Zandberg, J., Lips, C. J. M., and Jansz, H. S. (1985) FEBS Lett. 183, 403-407). The amino acid sequence of CGRP-I was obtained in medullary thyroid carcinoma extracts (Morris, H. R., Panico, M., Etienne, T., Tippins, J., Girgis, S. I., and MacIntyre, I. (1984) Nature 308, 746-748), but not in normal human tissues. The human CGRP-II peptide remained to be discovered. Here we have determined in the human spinal cord the amino acid composition and the partial amino acid sequence of the DNA-predicted CGRP-I and -II. The data indicate for the first time the existence of a second CGRP different from the known CGRP-I. CGRP-II has been identified in the central nervous system, pituitary, thyroid, and in medullary thyroid carcinoma as a major CGRP form together with CGRP-I.

  4. The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process

    Directory of Open Access Journals (Sweden)

    Poursina Narges

    2016-06-01

    Full Text Available Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content.

  5. Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles: in vitro and in vivo evaluation.

    Science.gov (United States)

    Cetin, Meltem; Aktas, Mustafa Sinan; Vural, Imran; Ozturk, Murat

    2012-01-01

    The main objective of this study was to prepare salmon calcitonin (sCT)-loaded Eudragit®RSPO, Eudragit®L100 and Eudragit®-poly(lactic-co-glycolic acid) blend nanoparticles for in vitro and in vivo evaluation as an oral drug delivery system. The prepared nanoparticles ranged in size from 179.7 to 308.9 nm with a polydispersity index between 0.051 and 2.75, and had surface charges ~ -11 to +6 mV. Efficient sCT encapsulation and release was observed with all the nanoparticle formulations. The polymer type was an important factor that influenced the release characteristics and the in vivo hypocalcemic effect. Nanoparticle formulations were also prepared with sodium taurodeoxycholate (NaTDC) and characterized. No statistically significant difference was noted between the hypocalcemic effect of any of the nanoparticle formulations with and without NaTDC (p > 0.05). The use of Eudragit®RSPO nanoparticles appears to be a potential approach for the oral delivery of sCT.

  6. 鲑鱼降钙素在膝关节骨关节炎中的应用%Application of salmon calcitonin in treating knee osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    李永刚; 唐海

    2012-01-01

    Objective To study the effect of salmon calcitonin in treating knee osteoarthritis.Methods Fortyeight cases of knee osteoarthritis were randomly divided into four groups,twelve cases each group.A group:acetaminophen+glucosamine hydrochloride,B group:meloxicam+glucosamine hydrochloride,C group:salmon calcitonin + glucosamine hydrochloride,D group:salmon calcitonin.Acetaminophen and meloxicam can stop as pain symptoms disappeared.Other drugs were treated for 12 weeks.A follow up was carried out to compare visual analogue score and 12-item short form health survey.Results Twelve weeks later,A,B,C,D four groups' visual analogue score decreased from before treatment 5.6±1.2,5.5±1.2,5.4±1.0,5.1±l.2 to 1.9±0.8,1.2±0.7,0.8±0.6,0.9±0.7,12-item short form health survey score from before treatment - 23.4±3.1,- 23.8±3.0,-24.8 ±3.8,-22.4±2.8 to -15.1±4.7、- 14.5±4.7,-9.3±6.2,-10.2±5.3.There was significant difference before and after treatment in every group(P< 0.05).The visual analogue scores of B,C and D group outweigh A group's (P< 0.05).A and B groups'scores of 12-item short form health survey were lower to C and D groups' ( P < 0.05 ).Conclusions Salmon calcitonin can relieve pain in treating knee osteoarthritis.%目的 分析鲑鱼降钙素治疗膝关节骨关节炎的临床疗效.方法 将膝关节骨关节炎患者48例按随机数字表法随机分为A、B、C、D4组,每组各12例.每组患者给予不同的药物治疗.A组:对乙酰氨基酚+盐酸氨基葡萄糖;B组:美洛昔康+盐酸氨基葡萄糖;C组:鲑鱼降钙素+盐酸氨基葡萄糖;D组:鲑鱼降钙索.对乙酰氨基酚及美洛昔康在疼痛症状消失后即可停用.其他药物疗程为12周.治疗前后记录对比疼痛视觉模拟评分,用12条目健康调查简表评价患者生活质量变化.结果 12周后,A、B、C、D4组疼痛视觉模拟评分由治疗前5.6±1.2、5.5±1.2、5.4±1.0、5.1±1.2降至1.9±0.8、1.2±0.7、0.8±0.6、0.9±0.7;12条日

  7. Noncovalent PEGylation: different effects of dansyl-, L-tryptophan-, phenylbutylamino-, benzyl- and cholesteryl-PEGs on the aggregation of salmon calcitonin and lysozyme.

    Science.gov (United States)

    Mueller, Claudia; Capelle, Martinus A H; Seyrek, Emek; Martel, Sophie; Carrupt, Pierre-Alain; Arvinte, Tudor; Borchard, Gerrit

    2012-06-01

    Protein aggregation is a major instability that can occur during all stages of protein drug production and development. Protein aggregates may compromise the safety and efficacy of the final protein formulation. In this paper, various new excipients [phenylbutylamino-, benzyl-, and cholesteryl-polyethylene glycols (PEGs)] and their use for the reduction of aggregation of salmon calcitonin (sCT) and hen egg-white lysozyme (HEWL) by noncovalent PEGylation are presented. The ability to suppress aggregation of sCT in various buffer systems at a 1:1 molar ratio was assessed by following changes in protein conformation and aggregation state over time. The results are compared with that of dansyl- and L-tryptophan (Trp)-PEGs described in earlier publications. Furthermore, the influence of the different PEG-based excipients on the aggregation of HEWL was measured. HEWL aggregation was completely suppressed in the presence of cholesteryl-PEGs (2 and 5 kDa), whereas deterioration was observed using benzyl-methoxy polyethylene glycols (mPEGs; 2 and 5 kDa). Phenylbutylamino- and Trp-mPEG (2 kDa), as well as dansyl-PEGs of different molecular weight prolonged the lag phase of aggregation and reduced the aggregation velocity of HEWL.

  8. Enhanced transbuccal salmon calcitonin (sCT) delivery: effect of chemical enhancers and electrical assistance on in vitro sCT buccal permeation.

    Science.gov (United States)

    Oh, Dong-Ho; Chun, Kyeung-Hwa; Jeon, Sang-Ok; Kang, Jeong-Won; Lee, Sangkil

    2011-10-01

    This study investigates the combined effect of absorption enhancers and electrical assistance on transbuccal salmon calcitonin (sCT) delivery, using fresh swine buccal tissue. We placed 200 IU (40 μg/mL) of each sCT formulation--containing various concentrations of ethanol, N-acetyl-L-cysteine (NAC), and sodium deoxyglycocholate (SDGC)--onto the donor part of a Franz diffusion cell. Then, 0.5 mA/cm(2) of fixed anodal current was applied alone or combined with chemical enhancers. The amount of permeated sCT was analyzed using an ELISA kit, and biophysical changes of the buccal mucosa were investigated using FT-IR spectroscopy, and hematoxylin-eosin staining methods were used to evaluate histological alteration of the buccal tissues. The flux (J(s)) of sCT increased with the addition of absorption enhancer groups, but it was significantly enhanced by the application of anodal iontophoresis (ITP). FT-IR study revealed that all groups caused an increase in lipid fluidity but only the groups containing SDGC showed statistically significant difference. Although the histological data of SDGC groups showed a possibility for tissue damage, the present enhancing methods appear to be safe. In conclusion, the combination of absorption enhancers and electrical assistance is a potential strategy for the enhancement of transbuccal sCT delivery.

  9. The effect of excipients on the stability and aerosol performance of salmon calcitonin dry powder inhalers prepared via the spray freeze drying process.

    Science.gov (United States)

    Poursina, Narges; Vatanara, Alireza; Rouini, Mohammad Reza; Gilani, Kambiz; Najafabadi, Abdolhossein Rouholamini

    2016-06-01

    Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content).

  10. Ultraviolet Resonance Raman spectroscopy used to study formulations of salmon calcitonin, a starch-peptide conjugate and TGF-β3.

    Science.gov (United States)

    Patois, E; Larmour, I A; Bell, S E J; Palais, C; Capelle, M A H; Gurny, R; Arvinte, T

    2012-06-01

    Ultraviolet Resonance Raman (UVRR) spectroscopy with excitation at 244 nm was investigated here as a possible useful tool for fast characterization of biopharmaceuticals. Studies were performed on three protein drugs: salmon calcitonin (sCT), starch-peptide conjugate, and transforming growth factor-β3 (TGF-β3) adsorbed onto solid granules of tricalcium phosphate (TCP). Secondary structure of sCT was investigated for solutions of 0.5mg/mL up to 200mg/mL, regardless of the turbidity or aggregation states. An increase in β-sheet content was detected when sCT solutions aggregated. UVRR spectroscopy also detected a small amount of residual organic solvent in a starch-peptide conjugate solution containing only 40 μg/mL of peptide. UVRR spectroscopy was then used to characterize a protein, TGF-β3, adsorbed onto solid granules of TCP at 50 and 250 μg/cm(3). This study shows that UVRR is suitable to characterize the protein formulations in a broad range of concentrations, in liquid, aggregated, and solid states.

  11. Loss of α-calcitonin gene-related peptide (αCGRP) reduces the efficacy of the Vestibulo-ocular Reflex (VOR).

    Science.gov (United States)

    Luebke, Anne E; Holt, Joseph C; Jordan, Paivi M; Wong, Yi Shan; Caldwell, Jillian S; Cullen, Kathleen E

    2014-07-30

    The neuroactive peptide calcitonin-gene related peptide (CGRP) is known to act at efferent synapses and their targets in hair cell organs, including the cochlea and lateral line. CGRP is also expressed in vestibular efferent neurons as well as a number of central vestibular neurons. Although CGRP-null (-/-) mice demonstrate a significant reduction in cochlear nerve sound-evoked activity compared with wild-type mice, it is unknown whether and how the loss of CGRP influence vestibular system function. Vestibular function was assessed by quantifying the vestibulo-ocular reflex (VOR) in alert mice. The loss of CGRP in (-/-) mice was associated with a reduction of the VOR gain of ≈50% without a concomitant change in phase. Using immunohistochemistry, we confirmed that, although CGRP staining was absent in the vestibular end-organs of null (-/-) mice, cholinergic staining appeared normal, suggesting that the overall gross development of vestibular efferent innervation was unaltered. We further confirmed that the observed deficit in vestibular function of null (-/-) mice was not the result of nontargeted effects at the level of the extraocular motor neurons and/or their innervation of extraocular muscles. Analysis of the relationship between vestibular quick phase amplitude and peak velocity revealed that extraocular motor function was unchanged, and immunohistochemistry revealed no abnormalities in motor endplates. Together, our findings show that the neurotransmitter CGRP plays a key role in ensuring VOR efficacy.

  12. A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference

    DEFF Research Database (Denmark)

    Gydesen, Sofie; Hjuler, Sara Toftegaard; Freving, Zenia

    2017-01-01

    amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated. Further, we elucidate weight-independent effects of KBP-089 using a weight-matched group. Key Results High fat diet fed......Background and Purpose Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges – hence, development of weight loss therapies with the ability to reduce the co-morbidities is key. Experimental Approach The effect of the dual...... rats were treated with KBP-089 s.c., at 0.625, 1.25, 2.5 µg∙kg-1 and vehicle resulting in a dose-dependent and sustained ~17% weight loss by the 2.5 µg∙kg-1 (p fat depot size and reduced lipid accumulation in muscle and liver. In Zucker Diabetic Fatty rats, KBP-089...

  13. Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe magnus of rats: an effect attenuated by naloxone.

    Science.gov (United States)

    Huang, Y; Brodda-Jansen, G; Lundeberg, T; Yu, L C

    2000-08-04

    The present study investigated the role of calcitonin gene-related peptide (CGRP) on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats, suggesting that it may contribute to physiological responses orchestrated by the NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was attenuated by following intra-NRM administration of 6 nmol of naloxone. The results indicate that CGRP and its receptors play an important role in anti-nociception, and there is a possible interaction between CGRP and opioid peptides in NRM of rats.

  14. Postnatal development of protein gene product 9.5 and calcitonin gene-related peptide immunoreactive nerve fibres in rat temporomandibular joint disc.

    Science.gov (United States)

    Ueki, N; Tanaka, E; Watanabe, M; Wakida, K; Takahashi, O; Uchida, T; Tanne, K

    2003-02-01

    Protein gene product 9.5 (PGP 9.5), an immunohistochemical marker of whole nerve fibres, and calcitonin gene-related peptide (CGRP), a marker of thin nerve fibres, were used to elucidate the postnatal development of nerve fibres in rat temporomandibular joint (TMJ) disc. At birth, PGP 9.5-immunoreactive nerve fibres exhibited running towards the central area of the disc, invading by approximately 95 m from the disc attachment. The nerve fibres existing inside the disc became longer during postnatal development. The number of nerve fibres in the disc increased in a progressive manner up to 40 days after birth. CGRP-immunoreactive nerve fibres also presented changes essentially similar to those of PGP 9.5-immunoreactive nerve fibres. However, the proportion of CGRP-immunoreactive nerve fibres to PGP 9.5-immunoreactive ones was approximately 80%, and remained constant up to 40 days after birth. In conclusion, the distribution and the number of nerve fibres are variable during postnatal development, although the ratio of thin nerve fibres remains invariable. It is emphasized that these changes of innervation in the TMJ are associated with the development of masticatory function.

  15. Effects of rizatriptan on the expression of calcitonin gene-related peptide and cholecystokinin in the periaqueductal gray of a rat migraine model.

    Science.gov (United States)

    Yao, Gang; Han, Ximei; Hao, Tingting; Huang, Qian; Yu, Tingmin

    2015-02-05

    Triptans are serotonin 5-hydroxytryptamine receptor 1B/D agonists that are highly effective in the treatment of migraine. We previously found that rizatriptan can reduce the expression of proenkephalin and P substance in the rat midbrain, suggesting that rizatriptan may exert its analgesic effects by influencing the endogenous pain modulatory system. Calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) are mainly responsible for antagonizing the analgesic effects of opioid peptides in the endogenous pain modulatory system. In this study, we investigated the effects of rizatriptan on the expression of CGRP and CCK in the periaqueductal gray (PAG), a key structure of the endogenous pain modulatory system, in a rat migraine model induced by nitroglycerin. We found that the mRNA and protein levels of CGRP and CCK in the PAG of migraine rats were significantly increased compared to those in control rats, and these levels were significantly reduced upon treatment with rizatriptan in migraine rats (P<0.05). Our results suggest that the expression of CGRP and CCK in the endogenous pain modulatory system may be increased during migraine attacks, which further antagonizes the analgesic effects of endogenous opioid peptides and induces sustained migraine. Rizatriptan, however, significantly reduces the levels of CGRP and CCK to enhance the inhibition of pain signals via the endogenous pain modulatory system, resulting in effective treatment of migraine.

  16. The potentiating effect of calcitonin gene-related peptide on transient receptor potential vanilloid-1 activity and the electrophysiological responses of rat trigeminal neurons to nociceptive stimuli.

    Science.gov (United States)

    Chatchaisak, Duangthip; Connor, Mark; Srikiatkhachorn, Anan; Chetsawang, Banthit

    2017-02-15

    Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP. An increase in TRPV1 levels was observed in CGRP-incubated TG organ cultures. CGRP potentiated capsaicin-induced increase in phosphorylated CaMKII levels in the TG organ cultures. The incubation of the trigeminal neurons with CGRP significantly increased the inward currents in response to capsaicin challenge, and this effect was inhibited by co-incubation with the CGRP receptor antagonist, BIBN4068BS or the inhibitor of protein kinase A, H-89. These findings reveal that CGRP acting on trigeminal neurons may play a significant role in facilitating cellular events that contribute to the peripheral sensitization of the TG in nociceptive transmission.

  17. Colocalization and shared distribution of endomorphins with substance P, calcitonin gene-related peptide, gamma-aminobutyric acid, and the mu opioid receptor.

    Science.gov (United States)

    Greenwell, Thomas N; Martin-Schild, Sheryl; Inglis, Fiona M; Zadina, James E

    2007-07-10

    The endomorphins are endogenous opioids with high affinity and selectivity for the mu opioid receptor (MOR, MOR-1, MOP). Endomorphin-1 (Tyr-Pro-Trp-Phe-NH(2); EM1) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2); EM2) have been localized to many regions of the central nervous system (CNS), including those that regulate antinociception, autonomic function, and reward. Colocalization or shared distribution (overlap) of two neurotransmitters, or a transmitter and its cognate receptor, may imply an interaction of these elements in the regulation of functions mediated in that region. For example, previous evidence of colocalization of EM2 with substance P (SP), calcitonin gene-related peptide (CGRP), and MOR in primary afferent neurons suggested an interaction of these peptides in pain modulation. We therefore investigated the colocalization of EM1 and EM2 with SP, CGRP, and MOR in other areas of the CNS. EM2 was colocalized with SP and CGRP in the nucleus of the solitary tract (NTS) and with SP, CGRP and MOR in the parabrachial nucleus. Several areas in which EM1 and EM2 showed extensive shared distributions, but no detectable colocalization with other signaling molecules, are also described.

  18. Evaluation of Clinical Findings and Treatment Results in Patients With Lumber Spinal Canal Stenosis and Osteoporosis Treated With Calcitonin and Physical Therapy

    Directory of Open Access Journals (Sweden)

    Hidayet Sarı

    2002-06-01

    Full Text Available Objective: The role of osteoporosis in the etiology of degenerative lumbar spinal canal stenosis is debatable. The aim of this study was to evaluate clinic as well as therapeutic results in subjects with osteoporosis combined with lumbar spinal canal stenosis (LSS. Material and Methods: The study was conducted in İ.Ü. Cerrahpaşa Medical Faculty PMR Department on 40 patients diagnosed as spinal canal stenosis . Lumbar canal was imaged by computerized tomography (CT. Bone mineral content (BMC was assessed by quantitative computerized tomography (QCT. Subjects were divided into three groups according to their BMC. Pain, motion, neurologic findings and walking distance were reevaluated after 1 months conservative treatment consisting of physical therapy IR, US, currents and exercises and medical treatment (100 IU Salmon Calcitonin injections and calcium. Results: Pain parameters showed significant improvement in Group II and III(low and very low BMC. Walking distance showed greatest increase in Group II and III, with these results being statistically significant. Conclusion: In subjects with combined LSS and osteoporosis one months conservative therapy resulted in significant improvements in pain and walking distance parameters, especially in groups with low BMC .We suggest that BMC should be considered and treated in patients with LSS.

  19. C-cell hyperplasia accompanying thyroid diseases other than medullary carcinoma: an immunocytochemical study by means of antibodies to calcitonin and somatostatin.

    Science.gov (United States)

    Scopsi, L; Di Palma, S; Ferrari, C; Holst, J J; Rehfeld, J F; Rilke, F

    1991-05-01

    Eighteen normal thyroid glands and unaffected thyroid tissue adjacent to 37 follicular cell-derived benign and malignant tumors and to ten thyroid metastases were studied immunocytochemically with calcitonin (CT) and prosomatostatin/somatostatin (SMS) antibodies. CT- and SMS-immunoreactive cells were found in 100% of cases, though with ample variations in number. Most but not all SMS-immunoreactive cells also contained CT. Diffuse and/or nodular C-cell hyperplasia was seen in 30% of pathological thyroid glands; in concomitance with follicular adenomas, the mean C-cell number more than doubled that found in normal glands. Furthermore the proportion of SMS-immunoreactive C-cells increased from about 1% of CT-immunoreactive cells in normal adult thyroid glands to 2.5% in follicular adenomas, 3% in follicular carcinomas, 4.6% in papillary carcinomas, and 5.7% in metastases. The findings suggest that C-cell hyperplasia may be causally related to pathologic disorders affecting follicular cells. Furthermore, the demonstration that the intrathyroidal SMS cell mass is readily affected by alterations of the follicular structure of the gland suggests a possible regulatory role of SMS in the thyroidal microenvironment.

  20. Diffusion of calcitonin through the wall of the root canal Avaliação da difusão da calcitonina através da dentina radicular

    Directory of Open Access Journals (Sweden)

    Selma Cristina Cury Camargo

    2004-03-01

    Full Text Available The aim of this study was to evaluate the in vitro diffusion of synthetic salmon calcitonin (CT, used as an intracanal medication, to the external root surface, with or without the presence of intact root cementum. Fifty-four human central incisors were used in the experiment, and were divided into two groups of 21 (test groups and two groups of 6 teeth (control groups. After root canal preparation, 10 ml of calcitonin was inserted within the root canal chamber. The root was sealed and made externally impermeable. Specimens were then placed in tubes with saline solution buffered with phosphates and stored at 37°C. The diffusion of calcitonin was measured after 1, 4 and 7 days. To count calcitonin present at the external media (PBS, ELISA test (an antigen-antibody reaction was used. Results showed that there was calcitonin diffusion through dentin in all of the test samples. The absence of cementum increased the diffusion of calcitonin (p=0.05. The highest counts of CT were obtained on day 7 for groups with or without cementum - showing a direct relation between time and diffusion of the medication.O presente estudo determinou in vitro a difusão da calcitonina sintética de salmão, como medicação intracanal, até a superfície externa radicular, com e sem a presença de cemento radicular. Foram utilizados cinqüenta e quatro incisivos centrais humanos, divididos em dois grupos com 21 dentes cada e dois grupos com 6 dentes cada (controle negativo. Após o preparo endodôntico, os dentes receberam 10 ml de calcitonina como medicação intracanal. Feitos o selamento e a impermeabilização externa da raiz, os espécimes foram acondicionados em tubos com solução salina tamponada com fosfatos e incubados em estufa a 37°C. Foram colhidas amostras da solução salina nos períodos de 1, 4 e 7 dias. Para a análise das soluções teste, utilizou-se teste ELISA. Os resultados mostram que existe a difusão da medicação testada até a superf

  1. 鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎OPF疗效分析%The study on treatment of vertebral osteoporotic fracture by salmon calcitonin and Heng Gu bone healing reagent

    Institute of Scientific and Technical Information of China (English)

    罗德军; 赵宏斌; 周旭; 董锡亮; 李林芝; 王文志; 熊海

    2011-01-01

    Objective To study effects of salmon calcitonin and Heng Gu bone healing reagent on vertebral osteoporotic fracture(OPF).Methods From Nov.2007 to Dec.2009,82 cases of vertebral OPF were treated.These cases were randomly divided into treatment group and control group.The treatment group(42 cascs)were treated with salmon calcitonin and Heng Gu bone healing reagent.The control group(40 cases)received salmon calcitonin only.Pain relief of the 2 groups wag compared.Results Before treatment,the 82 patients were scored 6-9 points by visual analogue scales(VAS)and pain scores of the 2 groups were similar (P>0.05).3 days,5 days,8 days and 15 days after treatment,VAS scores of the 2 groups were significantly different(P0.05).治疗后3、5、8、15 d,2组疼痛VAS评分分别经秩和检验差异有统计学意义(P<0.01).治疗组不但疼痛缓解快,3个月后复查骨矿物密度改善程度亦明显优于对照组.结论 鲑鱼降钙素联合恒古骨伤愈合剂治疗腰椎骨质疏松性骨折具有良好止痛和促进成骨作用,是一种安全、有效的方法.

  2. 鲑鱼降钙素在老年糖尿病并发骨质疏松中的疗效观察%Efficacy of salmon calcitonin in the treatment of elderly diabetes complicated with osteoporosis

    Institute of Scientific and Technical Information of China (English)

    董爱莲

    2012-01-01

      目的应用鲑鱼降钙素对患有糖尿病骨质疏松症的老年患者进行治疗,研究分析临床效果.方法抽取88例糖尿病骨质疏松症老年患者,将其分为对照组和治疗组.对照组采用钙尔奇 D 进行治疗;治疗组采用钙尔奇 D 与鲑鱼降钙素联合进行治疗.结果治疗组患者的症状改善效果明显优于对照组,相关指标在治疗前后的改善幅度明显大于对照组,差异均有统计学意义(P <0.05).结论应用鲑鱼降钙素对患有糖尿病骨质疏松症的老年患者进行治疗的临床效果较明显.%  Objective To study the clinical effect of salmon calcitonin in the treatment of elderly patients with diabetes complicated with osteoporosis. Methods 88 elderly patients with diabetic complicated with osteoporosis were divided into control and treatment group. The control group was treated with Caltrate D treatment. The treatment group was treated with Caltrate D and salmon calcitonin. Results The treatment group was significantly better than the control group. The improvement of related indicators before and after treatment was significantly greater than that of the control group(P <0.05). Conclusion The clinical effect is very obvious application of salmon calcitonin in the treatment of elderly patients with diabetes complicated with osteoporosis.

  3. Calcitonina monomérica plasmática e hipercalcemia em pacientes portadores de neoplasia pulmonar Monomeric plasmatic calcitonin and hypercalcemia in lung cancer patients

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    R. Coifman

    1997-06-01

    Full Text Available A calcitonina (CT é um hormônio peptídico relacionado ao metabolismo de cálcio produzido pelas células C da tiróide. Encontra-se com níveis plasmáticos bastante elevados no carcinoma medular de tiróide e mostra-se como excelente marcador dessa doença. No entanto, existem relatos na literatura que demonstraram níveis elevados deste peptídio em pacientes portadores de outras neoplasias, principalmente no carcinoma de pulmão. OBJETIVO. Avaliar a validade da dosagem da CT sérica como possível marcador tumoral em pacientes portadores de tumor de pulmão de diferentes tipos histológicos. MÉTODOS. Foram dosados CT plasmática e cálcio ionizado sanguíneo em 56 pacientes portadores de tumores malignos de pulmão. Para as dosagens de CT os autores utilizaram um método de radioimunoensaio específico, realizado após extração prévia do soro em coluna de sílica. RESULTADOS. Observou-se prevalência de hipercalcemia de 21,4%; apenas três (5,4% dos 56 pacientes investigados apresentaram níveis pouco elevados de calcitonina, e o restante manteve níveis normais ou indetectáveis do peptídio. CONCLUSÃO. Os resultados demonstram que, com a utilização de um método bastante específico para dosagem da calcitonina em sua forma monomérica, não se encontram níveis elevados deste hormônio em pacientes portadores de neoplasia pulmonar, desestimulando sua utilização como marcador tumoral nesta patologia.BACKGROUND. Calcitonin (CT is a peptidic hormone produced by the thyroid C cells and related to calcium metabolism. High plasmatic levels of this hormone are found in patients with medullary thyroid carcinoma, what makes it an excellent tumor marker for this disease. However, there are reports that showed an increase of plasmatic CT levels in patients with other tumors, mainly in lung cancer. PURPOSE. These data prompt us to investigate the validity of the CT level determinations as a potential tumor marker in different histologic

  4. Preparation and Evaluation of Enteric-Coated Chitosan Derivative-Based Microparticles Loaded with Salmon Calcitonin as an Oral Delivery System

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    Hiraku Onishi

    2016-09-01

    Full Text Available Background: The production of protein drugs has recently increased due to advances in biotechnology, but their clinical use is generally limited to parenteral administration due to low absorption in non-parenteral administration. Therefore, non-parenteral delivery systems allowing sufficient absorption draw much attention. Methods: Microparticles (MP were prepared using chitosan-4-thio-butylamidine conjugate (Ch-TBA, trimethyl-chitosan (TMC, and chitosan (Ch. Using salmon calcitonin (sCT as a model protein drug, Ch-TBA-, Ch-TBA/TMC (4/1-, and Ch-based MP were produced, and their Eudragit L100 (Eud-coated MP, named Ch-TBA-MP/Eud, Ch-TBA/TMC-MP/Eud, and Ch-MP/Eud, respectively, were prepared as oral delivery systems. These enteric-coated microparticles were examined in vitro and in vivo. Results: All microparticles before and after enteric coating had a submicron size (600–800 nm and micrometer size (1300–1500 nm, respectively. In vitro release patterns were similar among all microparticles; release occurred gradually, and the release rate was slower at pH 1.2 than at pH 6.8. In oral ingestion, Ch-TBA-MP/Eud suppressed plasma Ca levels most effectively among the microparticles tested. The relative effectiveness of Ch-TBA-MP/Eud to the intramuscular injection was 8.6%, while the sCT solution showed no effectiveness. Conclusion: The results suggest that Eud-coated Ch-TBA-based microparticles should have potential as an oral delivery system of protein drugs.

  5. The use of polyion complex micelles to enhance the oral delivery of salmon calcitonin and transport mechanism across the intestinal epithelial barrier.

    Science.gov (United States)

    Li, Na; Li, Xin-Ru; Zhou, Yan-Xia; Li, Wen-Jing; Zhao, Yong; Ma, Shu-Jin; Li, Jin-Wen; Gao, Ya-Jie; Liu, Yan; Wang, Xing-Lin; Yin, Dong-Dong

    2012-12-01

    The objective of the present study was to demonstrate the effect of polyanionic copolymer mPEG-grafted-alginic acid (mPEG-g-AA)-based polyion complex (PIC) micelles on enhancing the oral absorption of salmon calcitonin (sCT) in vivo and in vitro and identify the transepithelial transport mechanism of PIC micelles across the intestinal barrier. mPEG-g-AA was first successfully synthesized and characterized in cytotoxicity. The PIC micelles were approximately of 72 nm in diameter with a narrow distribution. The extremely significant enhancement of hypocalcemia efficacy of sCT-loaded PIC micelles in rats was evidenced by intraduodenal administration in comparison with sCT solution. The presence of mPEG-grafted-chitosan in PIC micelles had no favorable effect on this action in the referred content. In the Caco-2 transport studies, PIC micelles could significantly increase the permeability of sCT across Caco-2 monolayers without significantly affecting transepithelial electrical resistance values during the transport study. No evident alterations in the F-actin cytoskeleton were detected by confocal microscope observation following treatment of the cell monolayers with PIC micelles, which further certified the incapacity of PIC micelles to open the intercellular tight junctions. In addition, TEM observations showed that the intact PIC micelles were transported across the everted gut sac. These suggested that the transport of PIC micelles across Caco-2 cell monolayers involve a predominant transcytosis mechanism via endocytosis rather than paracellular pathway. Furthermore, PIC micelles were localized in both the cytoplasm and the nuclei observed by CLSM. Therefore, PIC micelles might be a potentially applicable tool for enhancing the oral absorption of cationic peptide and protein drugs.

  6. A hyaluronic acid-salmon calcitonin conjugate for the local treatment of osteoarthritis: chondro-protective effect in a rabbit model of early OA.

    Science.gov (United States)

    Mero, Anna; Campisi, Monica; Favero, Marta; Barbera, Carlo; Secchieri, Cynthia; Dayer, Jean M; Goldring, Mary B; Goldring, Steven R; Pasut, Gianfranco

    2014-08-10

    Osteoarthritis (OA) is characterized by chronic degeneration of joints, involving mainly the articular cartilage and the underlying bone, and severely impairing the quality of life of the patient. Although with limited efficacy, currently available pharmacological treatments for OA aim to control pain and to retard disease progression. Salmon calcitonin (sCT) is a drug which has been shown to have therapeutic effects in experimental arthritis by inhibiting both bone turnover and cartilage degradation and reducing the activities of matrix metalloproteinases (MMP). High molecular weight hyaluronic acid (HA) is used as a lubricant in OA therapy, and, interestingly, HA polymers may normalize the levels of MMP-1, -3 and -13. We demonstrated that sCT rapidly clears from the knee joint of rat animal model, after intra-articular (i.a.) administration, and it induces systemic effects. Here, sCT was conjugated to HA (200kDa) with the aim of prolonging the residence time of the polypeptide in the joint space by reducing its clearance. An aldehyde derivative of HA was used for N-terminal site-selective coupling of sCT. The activity of sCT was preserved, both in vitro and in vivo, after its conjugation and the i.a. injection of HA-sCT did not trigger any systemic effects in rats. The efficacy of HA-sCT treatment was tested in a rabbit OA model and clear chondro-protective effect was proven by macro- and microscopic assessments and histological findings. Our results indicate that HAylation of sCT increases the size of the polypeptide in a stable covalent manner and delays its passage into the blood stream. We conclude that HA conjugation prolongs the anti-catabolic effects of sCT in joint tissues, including the synovial membrane and cartilage.

  7. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain.

    Science.gov (United States)

    Romero-Reyes, Marcela; Pardi, Vanessa; Akerman, Simon

    2015-09-01

    Temporomandibular disorders (TMDs) are orofacial pains within the trigeminal distribution, which involve the masticatory musculature, the temporomandibular joint or both. Their pathophysiology remains unclear, as inflammatory mediators are thought to be involved, and clinically TMD presents pain and sometimes limitation of function, but often appears without gross indications of local inflammation, such as visible edema, redness and increase in temperature. Calcitonin gene-related peptide (CGRP) has been implicated in other pain disorders with trigeminal distribution, such as migraine, of which TMD shares a significant co-morbidity. CGRP causes activation and sensitization of trigeminal primary afferent neurons, independent of any inflammatory mechanisms, and thus may also be involved in TMD. Here we used a small molecule, selective CGRP receptor antagonist, MK-8825, to dissect the role of CGRP in inducing spontaneous nociceptive facial grooming behaviors, neuronal activation in the trigeminal nucleus, and systemic release of pro-inflammatory cytokines, in a mouse model of acute orofacial masseteric muscle pain that we have developed, as a surrogate of acute TMD. We show that CFA masseteric injection causes significant spontaneous orofacial pain behaviors, neuronal activation in the trigeminal nucleus, and release of interleukin-6 (IL-6). In mice pre-treated with MK-8825 there is a significant reduction in these spontaneous orofacial pain behaviors. Also, at 2 and 24h after CFA injection the level of Fos immunoreactivity in the trigeminal nucleus, used as a marker of neuronal activation, was much lower on both ipsilateral and contralateral sides after pre-treatment with MK-8825. There was no effect of MK-8825 on the release of IL-6. These data suggest that CGRP may be involved in TMD pathophysiology, but not via inflammatory mechanisms, at least in the acute stage. Furthermore, CGRP receptor antagonists may have therapeutic efficacy in the treatment of TMD, as they

  8. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma.

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    Jerzy Kaleczyc

    2010-11-01

    Full Text Available The aim of this study was to investigate the arrangement and chemical coding of enteric nerve structures in the human large intestine affected by cancer. Tissue samples comprising all layers of the intestinal wall were collected during surgery form both morphologically unchanged and pathologically altered segments of the intestine (n=15, and fixed by immersion in buffered paraformaldehyde solution. The cryostat sections were processed for double-labelling immunofluorescence to study the distribution of the intramural nerve structures (visualized with antibodies against protein gene-product 9.5 and their chemical coding using antibodies against somatostatin (SOM, substance P (SP and calcitonin gene-related peptide (CGRP. The microscopic observations revealed distinct morphological differences in the enteric nerve system structure between the region adjacent to the cancer invaded area and the intact part of the intestine. In general, infiltration of the cancer tissue resulted in the gradual (depending on the grade of invasion first decomposition and reduction to final partial or complete destruction and absence of the neuronal elements. A comparative analysis of immunohistochemically labeled sections (from the unchanged and pathologically altered areas revealed a statistically significant decrease in the number of CGRP-positive neurons and nerve fibres in both submucous and myenteric plexuses in the transitional zone between morphologically unchanged and cancer-invaded areas. In this zone, a decrease was also observed in the density of SP-positive nerve fibres in all intramural plexuses. Conversely, the investigations demonstrated statistically insignificant differences in number of SP- and SOM-positive neurons and a similar density of SOM-positive nerve fibres in the plexuses of the intact and pathologically changed areas. The differentiation between the potential adaptive changes in ENS or destruction of its elements by cancer invasion should be

  9. Impact of Food Components on in vitro Calcitonin Gene-Related Peptide Secretion—A Potential Mechanism for Dietary Influence on Migraine

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    Margaret Slavin

    2016-07-01

    Full Text Available Calcitonin gene-related peptide (CGRP is a pivotal messenger in the inflammatory process in migraine. Limited evidence indicates that diet impacts circulating levels of CGRP, suggesting that certain elements in the diet may influence migraine outcomes. Interruption of calcium signaling, a mechanism which can trigger CGRP release, has been suggested as one potential route by which exogenous food substances may impact CGRP secretion. The objective of this study was to investigate the effects of foods and a dietary supplement on two migraine-related mechanisms in vitro: CGRP secretion from neuroendocrine CA77 cells, and calcium uptake by differentiated PC12 cells. Ginger and grape pomace extracts were selected for their anecdotal connections to reducing or promoting migraine. S-petasin was selected as a suspected active constituent of butterbur extract, the migraine prophylactic dietary supplement. Results showed a statistically significant decrease in stimulated CGRP secretion from CA77 cells following treatment with ginger (0.2 mg dry ginger equivalent/mL and two doses of grape pomace (0.25 and 1.0 mg dry pomace equivalent/mL extracts. Relative to vehicle control, CGRP secretion decreased by 22%, 43%, and 87%, respectively. S-petasin at 1.0 μM also decreased CGRP secretion by 24%. Meanwhile, S-petasin and ginger extract showed inhibition of calcium influx, whereas grape pomace had no effect on calcium. These results suggest that grape pomace and ginger extracts, and S-petasin may have anti-inflammatory propensity by preventing CGRP release in migraine, although potentially by different mechanisms, which future studies may elucidate further.

  10. Design of salmon calcitonin particles for nasal delivery using spray-drying and novel supercritical fluid-assisted spray-drying processes.

    Science.gov (United States)

    Cho, Wonkyung; Kim, Min-Soo; Jung, Min-Sook; Park, Junsung; Cha, Kwang-Ho; Kim, Jeong-Soo; Park, Hee Jun; Alhalaweh, Amjad; Velaga, Sitaram P; Hwang, Sung-Joo

    2015-01-15

    The overall aim of this study was to prepare a nasal powder formulation of salmon calcitonin (sCT) using an absorption enhancer to improve its bioavailability. In this work, powder formulations for nasal delivery of sCT were studied using various absorption enhancers and stabilizers. Powders were prepared by two different methods: conventional spray-drying (SD) and novel supercritical fluid-assisted spray-drying (SASD) to investigate the role of CO2 in the particle formation process. The prepared sCT powder formulations were characterized by several analyses; powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), and the Fourier transform infrared (FT-IR) spectroscopy method. The particle size distribution was also evaluated. In vivo absorption tests were carried out in Sprague-Dawley rat using the prepared powder formulations, and the results were compared to those of raw sCT. Quantitative analysis by high-performance liquid chromatography (HPLC) indicated that sCT was chemically stable after both the SD and SASD processes. Results of PXRD, SEM, and FT-IR did not indicate a strong interaction or defragmentation of sCT. The in vivo absorption test showed that SD- and SASD-processed sCT powders increased the bioavailability of the drug when compared to the nasal administration of raw sCT. In addition, SASD-processed sCT exhibited higher nasal absorption when compared with SD-processed sCT in all formulations due to a reduction of particle size. The results from this study illustrate that the preparation of nasal powders using the SASD process could be a promising approach to improve nasal absorption of sCT.

  11. Changes in the Expressions of Iba1 and Calcitonin Gene-Related Peptide in Adjacent Lumbar Spinal Segments after Lumbar Disc Herniation in a Rat Model.

    Science.gov (United States)

    Cho, Hee Kyung; Ahn, Sang Ho; Kim, So-Yeon; Choi, Mi-Jung; Hwang, Se Jin; Cho, Yun Woo

    2015-12-01

    Lumbar disc herniation is commonly encountered in clinical practice and can induce sciatica due to mechanical and/or chemical irritation and the release of proinflammatory cytokines. However, symptoms are not confined to the affected spinal cord segment. The purpose of this study was to determine whether multisegmental molecular changes exist between adjacent lumbar spinal segments using a rat model of lumbar disc herniation. Twenty-nine male Sprague-Dawley rats were randomly assigned to either a sham-operated group (n=10) or a nucleus pulposus (NP)-exposed group (n=19). Rats in the NP-exposed group were further subdivided into a significant pain subgroup (n=12) and a no significant pain subgroup (n=7) using mechanical pain thresholds determined von Frey filaments. Immunohistochemical stainings of microglia (ionized calcium-binding adapter molecule 1; Iba1), astrocytes (glial fibrillary acidic protein; GFAP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid 1 (TRPV1) was performed in spinal dorsal horns and dorsal root ganglions (DRGs) at 10 days after surgery. It was found immunoreactivity for Iba1-positive microglia was higher in the L5 (P=0.004) dorsal horn and in the ipsilateral L4 (P=0.009), L6 (P=0.002), and S1 (P=0.002) dorsal horns in the NP-exposed group than in the sham-operated group. The expression of CGRP was also significantly higher in ipsilateral L3, L4, L6, and S1 segments and in L5 DRGs at 10 days after surgery in the NP-exposed group than in the sham-operated group (Plumbar disc herniation upregulates microglial activity and CGRP expression in many adjacent and ipsilateral lumbar spinal segments.

  12. Alpha-Calcitonin Gene-Related Peptide Can Reverse The Catabolic Influence Of UHMWPE Particles On RANKL Expression In Primary Human Osteoblasts

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    Max D. Kauther, Jie Xu, Christian Wedemeyer

    2010-01-01

    Full Text Available Background and purpose: A linkage between the neurotransmitter alpha-calcitonin gene-related peptide (alpha-CGRP and particle-induced osteolysis has been shown previously. The suggested osteoprotective influence of alpha-CGRP on the catabolic effects of ultra-high molecular weight polyethylene (UHMWPE particles is analyzed in this study in primary human osteoblasts. Methods: Primary human osteoblasts were stimulated by UHMWPE particles (cell/particle ratios 1:100 and 1:500 and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M. Receptor activator of nuclear factor-κB ligand (RANKL and osteoprotegerin (OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. Results: Particle stimulation leads to a significant dose-dependent increase of RANKL mRNA in both cell-particle ratios and a significant down-regulation of OPG mRNA in cell-particle concentrations of 1:500. A significant depression of alkaline phosphatase was found due to particle stimulation. Alpha-CGRP in all tested concentrations showed a significant depressive effect on the expression of RANKL mRNA in primary human osteoblasts under particle stimulation. Comparable reactions of RANKL protein levels due to particles and alpha-CGRP were found by Western blot analysis. In cell-particle ratios of 1:100 after 24 hours the osteoprotective influence of alpha-CGRP reversed the catabolic effects of particles on the RANKL expression. Interpretation: The in-vivo use of alpha-CGRP, which leads to down-regulated RANKL in-vitro, might inhibit the catabolic effect of particles in conditions of particle induced osteolysis.

  13. Calcitonin gene-related peptide promotes the expression of osteoblastic genes and activates the WNT signal transduction pathway in bone marrow stromal stem cells

    Science.gov (United States)

    ZHOU, RI; YUAN, ZHI; LIU, JIERONG; LIU, JIAN

    2016-01-01

    Calcitonin gene-related peptide (CGRP) is known to induce osteoblastic differentiation and alkaline phosphatase activity in bone marrow stromal stem cells (BMSCs). However, it has remained elusive whether this effect is mediated by CGRP receptors directly or whether other signaling pathways are involved. The present study assessed the possible involvement of the Wnt/β-catenin signaling pathway in the activation of CGRP signaling during the differentiation of BMSCs. First, the differentiation of BMSCs was induced in vitro and the expression of CGRP receptors was examined by western blot analysis. The effects of exogenous CGRP and LiCl, a stimulator of the Wnt/β-catenin signaling pathway, on the osteoblastic differentiation of BMSCs were assessed; furthermore, the expression of mRNA and proteins involved in the Wnt/β-catenin signaling pathway was assessed using quantitative PCR and western blot analyses. The results revealed that CGRP receptors were expressed throughout the differentiation of BMSCs, at days 7 and 14. Incubation with CGRP and LiCl led to the upregulation of the expression of osteoblastic genes associated with the Wnt/β-catenin pathway, including the mRNA of c-myc, cyclin D1, Lef1, Tcf7 and β-catenin as well as β-catenin protein. However, the upregulation of these genes and β-catenin protein was inhibited by CGRP receptor antagonist or secreted frizzled-related protein, an antagonist of the Wnt/β-catenin pathway. The results of the present study therefore suggested that the Wnt/β-catenin signaling pathway may be involved in CGRP- and LiCl-promoted osteoblastic differentiation of BMSCs. PMID:27082317

  14. Phenotypic alterations of neuropeptide Y and calcitonin gene-related peptide-containing neurons innervating the rat temporomandibular joint during carrageenan-induced arthritis

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    J.P. Damico

    2012-10-01

    Full Text Available The aim of this study was to identify immunoreactive neuropeptide Y (NPY and calcitonin gene-related peptide (CGRP neurons in the autonomic and sensory ganglia, specifically neurons that innervate the rat temporomandibular joint (TMJ. A possible variation between the percentages of these neurons in acute and chronic phases of carrageenan-induced arthritis was examined. Retrograde neuronal tracing was combined with indirect immunofluorescence to identify NPY-immunoreactive (NPY-IR and CGRP- immunoreactive (CGRP-IR neurons that send nerve fibers to the normal and arthritic temporomandibular joint. In normal joints, NPY-IR neurons constitute 78±3%, 77±6% and 10±4% of double-labeled nucleated neuronal profile originated from the superior cervical, stellate and otic ganglia, respectively. These percentages in the autonomic ganglia were significantly decreased in acute (58±2% to superior cervical ganglion and 58±8% to stellate ganglion and chronic (60±2% to superior cervical ganglion and 59±15% to stellate ganglion phases of arthritis, while in the otic ganglion these percentages were significantly increased to 19±5% and 13±3%, respectively. In the trigeminal ganglion, CGRP-IR neurons innervating the joint significantly increased from 31±3% in normal animals to 54±2% and 49±3% in the acute and chronic phases of arthritis, respectively. It can be concluded that NPY neurons that send nerve fibers to the rat temporomandibular joint are located mainly in the superior cervical, stellate and otic ganglia. Acute and chronic phases of carrageenan-induced arthritis lead to an increase in the percentage of NPY-IR parasympathetic and CGRP-IR sensory neurons and decrease in the percentage of NPY-IR sympathetic neurons related to TMJ innervation.

  15. Relaxant effect of the calcitonin gene-related peptide (CGRP) on the nonpregnant and pregnant rat uterus. Comparison with vascular tissue.

    Science.gov (United States)

    Anouar, A; Schirar, A; Germain, G

    1998-04-01

    To explore the role of calcitonin gene-related peptide (CGRP) in rat pregnancy, we determined the density of myometrial CGRP-encoded nerve fibre terminals and examined, in an organ bath, the relaxant effect of the peptide on uterine strips near parturition. Comparisons were made with the uterus and aorta of nonpregnant rats. In the myometrium, CGRP immunoreactive nerve fibers were abundant in nonpregnant rats and scarce at the parturient stage. In the aorta there was no variation in the density of CGRP fibres with gestation. In nonpregnant rats only, CGRP relaxed spontaneous and tetrodotoxin (TTX)-sensitive electrically-evoked uterine contractions (EC50 40 nM, Emax 80%). The effect was antagonized by CGRP[8-37] (pKB 6.47) but was not affected by either blockers of nitricoxid synthase or ATP-sensitive potassium channels. CGRP was also able to relax contractions evoked by direct depolarization of the cells (TTX-insensitive contractions) (EC50, 2 nM, Emax 70%). In aorta contracted with arginine vasopressin, CGRP-induced relaxation was the same in nonpregnant and parturient animals. It was antagonized by CGRP [8-371 (pKB 6.90) and was abolished in presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME). Amylin neither relaxed the uterus nor the aorta. In pregnant rats, the relaxant effect of CGRP on the uterus was limited on day 21 and was totally absent on day 22 of gestation. We conclude that the primary relaxant effect of CGRP on the uterus occurs at the level of myometrial smooth muscle cells. In the myometrium, gestation decreases CGRP innervation and impairs the relaxant responses to CGRP. Such changes are not observed in vascular tissues like aorta.

  16. Effects of tegaserod on Fos,substance P and calcitonin gene-related peptide expression induced by colon inflammation in lumbarsacral spinal cord

    Institute of Scientific and Technical Information of China (English)

    Yi-Ning Sun; Jin-Yan Luo

    2004-01-01

    AIM: To investigate the mechanisms of tegaserod, a partial 5-HT4 agonist, in reducing visceral sensitivity by observing Fos, substance P (SP) and calcitonin gene-related peptide (CGRP) expression in the lumbarsacral spinal cord inducedby colonic inflammation in rats.METHODS: Twenty-four male rats with colonic inflammation induced by intraluminal instillation of trinitrobenzenesulfonic acid (TNBS) were divided into 3 groups. Treatment group Treatment group 2: intra-gastric administration of tegaserod,saline, 2.0 mL/d. After 7 d of intra-gastric administration,lumbarsacral spinal cord was removed and processed for Fos, SP and CGRP immunohistochemistry.RESULTS: In rats of the control group, the majority of Fos labeled neurons was localized in deeper laminae of the lumbarsacral spinal cord (L5-S1). SP and CGRP were primarily expressed in the superficial laminae of the spinal cord after TNBS injection. Intra-gastric administration of tegaserod neurons (22.0±7.7) and SP density (12.5±1.4) in the dorsal horn in the lumbarsacral spinal cord compared to those of the control group (62.2±18.9, 35.9±8.9, P<0.05). However,CGRP content in dorsal horn did not significantly reduce in rats of treatment group 1 (1.2±1.1) compared to that of the control group (2.8±2.4, P>0.05). Neither Fos expression nor SP or CGRP density in the dorsal horn significantly declined in rats of treatment group 2 compared to those of the control group (P>0.05).CONCLUSION: Tegaserod can significantly reduce Fos labeled neurons in the lumbarsacral spinal cord induced by colonic inflammation. Tegaserod may reduce visceral sensitivity by inhibiting SP expression in the dorsal horn of spinal cord.

  17. Mitogen-activated protein kinase pathways are involved in the upregulation of calcitonin gene-related peptide of rat trigeminal ganglion after organ culture.

    Science.gov (United States)

    Lei, Li; Yuan, Xingyun; Wang, Shaolan; Zhang, Fujun; Han, Yan; Ning, Qilan; Luo, Guogang; Lu, Shemin

    2012-09-01

    The trigeminal ganglion (TG) can express and release calcitonin gene-related peptide (CGRP), an important neuropeptide that plays a crucial role in migraine attack and cluster headache. Activation of rat TG increases CGRP expression. However, the regulatory mechanism of CGRP expression in TG neurons remains to be explored. This study aims to evaluate the involvement of mitogen-activated protein kinase (MAPK) pathways in CGRP upregulation after rat TG organ culture. Rat TG was cultured alone for 24 h or cultured in combination with MAPK inhibitors, tumor necrosis factor α (TNF-α), or interleukin 1β (IL-1β) for 24 h. CGRP protein was determined using immunohistochemistry. The mRNA levels of CGRP, TNF-α, and IL-1β were analyzed through real-time quantitative polymerase chain reaction. MAPK phosphorylation was detected via western blot. After rat TG organ culture, the expressions of CGRP, TNF-α, and IL-1β were upregulated at 24 h. The phosphorylation of extracellular signal-regulated kinases (ERK1/2), P38, and c-jun N-terminal kinases (JNK) significantly increased at 30 min compared with fresh rat TG. In addition, both CGRP expression and phosphorylation of ERK1/2, P38, and JNK were enhanced obviously after rat TG treatment with TNF-α or IL-1β compared with fresh rat TG. However, they decreased markedly after rat TG pretreatment with PD98059 (ERK1/2 inhibitor), SB203580 (P38 inhibitor), or SP600125 (JNK inhibitor) compared with rat TG co-culture with TNF-α or IL-1β. In conclusion, the elevated CGRP expression after rat TG organ culture can be regulated via MAPK pathways. The findings provide insight into the molecular mechanisms and experimental evidence for therapeutic targets of migraine.

  18. An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress.

    Science.gov (United States)

    Smillie, Sarah-Jane; King, Ross; Kodji, Xenia; Outzen, Emilie; Pozsgai, Gabor; Fernandes, Elizabeth; Marshall, Nichola; de Winter, Patricia; Heads, Richard J; Dessapt-Baradez, Cecile; Gnudi, Luigi; Sams, Anette; Shah, Ajay M; Siow, Richard C; Brain, Susan D

    2014-05-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP. Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of αCGRP in hypertension may have been previously underestimated.

  19. Effect of Recombinant Saccharomyces cerevisiae Expressing Salmon Calcitonin on Osteoclast Culture in vitro%转鲑鱼降钙素基因酵母对体外培养破骨细胞的影响

    Institute of Scientific and Technical Information of China (English)

    姜勇; 张辉; 王鹏; 赵喜喜; 徐科凤; 王健; 张学成

    2011-01-01

    用机械分离的方法获得新生Wistar大鼠的破骨细胞,在培养液中分别加人经肠激酶酶切的转鲑鱼降钙素基因酵母的上清液和密钙息(Miacalcic,鲑鱼降钙素注射液),以HE染色观察破骨细胞形态,Image-Pro Plus图像软件分析骨片上骨吸收陷窝的面积,骨片培养7天,吸收陷窝结果显示,转鲑鱼降钙素对破骨细胞吸收功能具有明显的抑制作用.%The osteoclasts of new born Wistar mice were obtained by mechanical separation. The recom binant Saccharomyces cerevisiae expressing salmon calcitonin and restricted by enterokinase and Miacalcic were added into the culture solution respectively. The osteoclasts were observed by HE staining. After cultured for seven days, the area of bone resorption pits was analyzed by Image - Pro Plus image software. The results showed that the recombinant Saccharomyces cerevisiae expressing salmon calcitonin had obvious inhibitory ac tion to the absorption function of osteoclasts.

  20. 降钙素原在全身炎症反应综合征中的临床价值%Calcitonin original clinical value in systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    张志强

    2015-01-01

    Objective To explore the serum calcitonin original value in the diagnosis of systemic inflammatory response syndrome.Methods Select 120 cases of patients with systemic inflammatory response syndrome as the research object, the bacteria infection in 77 cases (group A), the bacterial infection 43 cases (group B), test and compare the two groups of patients the WBC (white blood cell count), hs - CRP (hypersensitive c-reactive protein), PCT (calcitonin former) level.Results A group of patients with PCT were significantly higher than that of group B, statistically significant difference (P 0.05);A组患者的PCT水平显著高于B组,P<0.05,差异具有统计学意义(P<0.05)。患者危重评分与PCT水平呈负相关(r=-0.798,P<0.05)。结论:在全身炎症反应综合征的病原学诊断中,PCT的诊断价值优于中心粒细胞占比、WBC、hs-CRP,是敏感性较高的一种血清学标志,具有重要的临床应用价值。

  1. Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells.

    Science.gov (United States)

    Tsukamoto, Manabu; Menuki, Kunitaka; Murai, Teppei; Hatakeyama, Akihisa; Takada, Shinichiro; Furukawa, Kayoko; Sakai, Akinori

    2016-04-01

    This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the

  2. Intermolecular interactions between salmon calcitonin, hyaluronate, and chitosan and their impact on the process of formation and properties of peptide-loaded nanoparticles.

    Science.gov (United States)

    Umerska, Anita; Corrigan, Owen I; Tajber, Lidia

    2014-12-30

    The principal aim of this work was to study the formulation of a ternary complex comprising salmon calcitonin (sCT), hyaluronate (HA), and chitosan (CS) in a nanoparticle (NP) format. As interactions between the constituents are possible, their presence and component mass mixing ratio (MMR) and charge mixing ratio (CMR) were investigated to tune the properties of NPs. Intermolecular interactions between sCT and HA as well as sCT and CS were studied by infrared spectroscopy (FTIR) and dynamic viscosity. The impact of MMR, CMR, and HA molecular weight on the sCT loading capacity in NPs and in vitro release properties was determined. sCT complexes to HA via electrostatic interactions and a support for hydrophobic interactions between sCT and HA as well as sCT and CS was found by FTIR. The sCT/HA complex is soluble but, depending on the mass mixing ratio between sCT and HA, NPs and microparticles were also formed indicative of associative phase separation between HA and sCT. The negatively charged HA/CS/sCT NPs were characterized by very high values (above 90%) of peptide association for the systems tested. Also, high sCT loading up to 50% were achieved. The peptide loading capacity and in vitro release properties were dependent on the NP composition. The zeta potential of the NPs without sCT was negative and ranging from -136 to -36 mV, but increased to -84 to -19 mV when the peptide was loaded. The particle size was found to be smaller and ranging 150-230 nm for sCT/NPs in comparison to NPs without sCT (170-260 nm). Short-term storage studies in liquid dispersions showed that the colloidal stability of NPs was acceptable and no release of sCT was observed for up to 3 days. In conclusion, a range of NP systems comprising sCT, HA, and CS was successfully developed and characterized. Such NPs may be considered as a suitable nanoparticulate format for the delivery of sCT.

  3. In vitro and in vivo preclinical evaluation of a minisphere emulsion-based formulation (SmPill®) of salmon calcitonin.

    Science.gov (United States)

    Aguirre, Tanira A S; Rosa, Mónica; Coulter, Ivan S; Brayden, David J

    2015-11-15

    Salmon calcitonin (sCT, MW 3432Da) is a benchmark molecule for an oral peptide delivery system because it is degraded and has low intestinal epithelial permeability. Four dry emulsion minisphere prototypes (SmPill®) containing sCT were co-formulated with permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10) or coco-glucoside (CG), or with a pH acidifier, citric acid (CA). Minispheres protected sCT from thermal degradation and the released sCT retained high bioactivity, as determined by cyclic AMP generation in T47D cells. Pre-minisphere emulsions of PEs combined with sCT increased absolute bioavailability (F) compared to native sCT following rat intra-jejunal (i.j.) and intra-colonic (i.c.) loop instillations, an effect that was more pronounced in colon. Minispheres corresponding to ~2000I.U. (~390μg) sCT/kg were instilled by i.j. or i.c. instillations and hypocalcaemia resulted from all prototypes. The absolute F (i.j.) of sCT was 11.0, 4.8, and 1.4% for minispheres containing NaTDC (10μmol/kg), CG (12μmol/kg) or CA (32μmol/kg) respectively. For i.c. instillations, the largest absolute F (22% in each case) was achieved for minispheres containing either C10 (284μmol/kg) or CG (12μmol/kg), whilst the absolute F was 8.2% for minispheres loaded with CA (32μmol/kg). In terms of relative F, the best data were obtained for minispheres containing NaTDC (i.j.), a 4-fold increase over sCT solution, and also for either C10 or CG (i.c.), where there was a 3-fold increase over sCT solution. Histology of instilled intestinal loops indicated that neither the minispheres nor components thereof caused major perturbation. In conclusion, selected SmPill® minisphere formulations may have the potential to be used as oral peptide delivery systems when delivered to jejunum or colon.

  4. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway.

    Science.gov (United States)

    Wulf-Johansson, H; Amrutkar, D V; Hay-Schmidt, A; Poulsen, A N; Klaerke, D A; Olesen, J; Jansen-Olesen, I

    2010-06-02

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine pathophysiology. Here we study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS11021 on CGRP release from isolated TG and TNC was investigated. By RT-PCR, BK(Ca) channel mRNA was detected in the TG and the TNC. A significant difference in BK(Ca) channel mRNA transcript levels were found using qPCR between the TNC as compared to the TG. The BK(Ca) channel protein was more expressed in the TNC as compared to the TG shown by western blotting. Immunohistochemistry identified BK(Ca) channels in the nerve cell bodies of the TG and the TNC. The beta2- and beta4-subunit proteins were found in the TG and the TNC. They were both more expressed in the TNC as compared to TG shown by western blotting. In isolated TNC, the BK(Ca) channel blocker iberiotoxin induced a concentration-dependent release of CGRP that was attenuated by the BK(Ca) channel opener NS11021. No effect on basal CGRP release was found by NS11021 in isolated TG or TNC or by iberiotoxin in TG. In conclusion, we found both BK(Ca) channel mRNA and protein expression in the TG and the TNC. The BK(Ca) channel protein and the modulatory beta2- and beta4-subunt proteins were more expressed in the TNC than in the TG. Iberiotoxin induced an increase in CGRP release from the TNC that was attenuated by NS11021. Thus, BK(Ca) channels might have a role in trigeminovascular pain transmission.

  5. A calcitonin receptor (CALCR) single nucleotide polymorphism is associated with growth performance and bone integrity in response to dietary phosphorus deficiency.

    Science.gov (United States)

    Alexander, L S; Qu, A; Cutler, S A; Mahajan, A; Rothschild, M F; Cai, W; Dekkers, J C; Stahl, C H

    2010-03-01

    Although concerns over the environmental impact of excess P in the excreta from pig production and governmental regulations have driven research toward reducing dietary supplementation of P to swine diets for over a decade, recent dramatic increases in feed costs have further motivated researchers to identify means to further reduce dietary P supplementation. We have demonstrated that genetic background impacts P utilization in young pigs and have identified genetic polymorphisms in several target genes related to mineral utilization. In this study, we examined the impact of a SNP in the calcitonin receptor gene (CALCR) on P utilization in growing pigs. In Exp. 1, 36 gilts representing the 3 genotypes identified by this CALCR SNP (11, 12, and 22) were fed a P-adequate (PA) or a marginally P-deficient (approximately 20% less available P; PD) diet for 14 wk. As expected, P deficiency reduced plasma P concentration, bone strength, and mineral content (P < 0.05). However, the dietary P deficiency was mild enough to not affect the growth performance of these pigs. A genotype x dietary P interaction (P < 0.05) was observed in measures of bone integrity and mineral content, with the greatest reduction in bone strength and mineral content due to dietary P deficiency being associated with the allele 1. In Exp. 2, 168 pigs from a control line and low residual feed intake (RFI) line were genotyped for the CALCR SNP and fed a PA diet. As expected, pigs from the low RFI line consumed less feed but also gained less BW when compared with the control line (P < 0.05). Although ADFI did not differ between genotypes, pigs having the 11 genotype gained less BW (P < 0.05) than pigs having the 12 or 22 genotypes. Pigs of the 11 and 12 genotypes had bones that tolerated greater load when compared with animals having the 22 genotype (P < 0.05). A similar trend was observed in bone modulus and ash % (P < 0.10). These data are supportive of the association of this CALCR SNP with bone

  6. Effect of calcitonin gene related peptide regulated nuclear factor kappa B signal transduction on c-kit+ cardiac stem cells in hypoxia state

    Directory of Open Access Journals (Sweden)

    Xian-ping LONG

    2015-11-01

    Full Text Available Objective To investigate the effects of calcitonin gene-related peptide (CGRP on the apoptosis of c-kit+ cardiac stem cells in hypoxia. Methods Ischemia and hypoxia models of c-kit+ cardiac stem cells were reproduced in vitro. The models were divided into hypoxia+CGRP group, hypoxia+CGRP8-37 (antagonist of CGRP group, hypoxia control group, normal oxygen group, and hypoxia+BAY11-7082 [antagonist of nuclear factor kappa B (NF-κB] group. NF-κB translocation after hypoxia was detected by immunofluorescence, and NF-κB channel proteins were determined with Western blotting. The NF-κB translocation and the expression of NF-κB channel proteins after CGRP intervention were detected, and the cell apoptosis rate after intervention was determined with flow cytometry in each group. Results Under hypoxia the NF-κB signal pathway was activated, and nuclear translocation occurred in NF-κBP65 (red fluorescence. Compared with hypoxia control group, the expressions of NF-κB related proteins such as P-I-κB, NF-κBP65 and NF-κBP50 decreased obviously (P<0.05. Compared with the hypoxia+CGRP group, the expressions of NF-κB related proteins increased significantly (P<0.05 as mentioned above in hypoxia+CGRP8-37 group. Both the early and late apoptotic rates declined in hypoxia+CGRP group compared with that of hypoxia control group (P<0.05, however, the early apoptotic rate increased markedly in hypoxia+CGRP8-37 group as compared with that of hypoxia+CGRP group (P<0.05. Conclusion Under hypoxia, CGRP may regulate the NF-κB signal pathway, and at the same time suppress the apoptosis of c-kit+ cardiac stem cells. DOI: 10.11855/j.issn.0577-7402.2015.10.03

  7. In vitro induction of oocyte maturation and steroidogenesis by gonadotropins, insulin, calcitonin and growth factor in an estuarine flat head grey mullet, Mugil cephalus L.

    Science.gov (United States)

    Das, Puranjan; Pramanick, Kousik; Mukherjee, Dilip; Maiti, B R

    2014-02-01

    In this article, an in vitro investigation was carried out to ascertain the roles of hormones and growth factor in the inductions of oocyte maturation and steroidogenesis of the postvitellogenic follicles in an Indian estuarine grey mullet, Mugil cephalus L. Oocyte maturation was evaluated by scoring the germinal vesicle breakdown (GVBD) percent of the postvitellogenic follicles. All the sex [17α,20β-dihydroxy-4-pregnane-3-one (DHP), estradiol 17β (E₂), progesterone (P), 17α-OH progesterone (17-OH-P) and testosterone] and other [bovine-insulin and salmon-calcitonin, human chorionic gonadotropin (hCG), luteinizing hormone (LH) or hCG+DHP] hormones and insulin-like growth factor-I (IGF-I) significantly increased GVBD% in 9 h culture. DHP had a maximum effect (75 %) compared to other effectors. Some effectors (hCG: 82.14 %, LH: 78.94 %, hCG plus DHP: 81.81 %, E₂: 80 % and IGF-I: 74.19 %) including DHP (79 %) further increased GVBD% in 15-h culture. All the hormones (except DHP) and IGF-I increased DHP, E₂ and testosterone productions by the postvitellogenic ovarian follicles in vitro. DHP and testosterone productions were increased with the increase of incubation time from 9 h through 15 h. E₂ production was not further increased beyond 12 h. DHP production was highest by hCG compared to other effectors. The hCG of all the test compounds was most effective in both the induction of GVBD% and steroid production. DHP is the most potent inducer of oocyte maturation in Indian estuarine flat head grey mullet. Involvement of estrogen in mullet oocyte maturation is indicated. hCG, like DHP, is equally potent and induces oocyte maturation via DHP production in vitro. hCG with DHP has synergistic action on oocyte maturation in mullet ovary. Interplay of several hormones (hCG, LH, and probably E₂ and testosterone) and IGF-I on oocyte maturation is suggested in the mullet.

  8. Effects of Qindan Capsule(芩丹胶囊) on Blood Pressure,Endothelin, Calcitonin Gene-related Peptide and Angiotensin-Ⅱ in Spontaneous Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To observe the hypotensive effects of Qindan Capsule (芩丹胶囊, QC) on spontaneous hypertensive rats (SHR) and its effect on the contents of endothelin (ET), calcitonin gene-related peptide (CGRP) and angiotensin-Ⅱ (Ang-Ⅱ ) in plasma and vascular tissues, and to investigate the possible mechanism of QC in lowering blood pressure. Methods: Forty SHRs were divided into 5 groups: the high dosage QC group [QCHD, 750 mg/(kg·d)], the low dosage QC group [QCLD, 150 mg/(kg·d)], the Niuhuang Jiangya Pill group [牛黄降压丸, NJP, 200 mg/(kg·d)], the Captopril group [ 15 mg/(kg·d)]and the model group, 8 in each group. Meanwhile, a normal control group consisting of 8 Wistar-Kyoto (WKY) rats was set up also. All the rats were administered with medicine through gastrogavage. Systolic blood pressure (SBP),level of ET, CGRP and Ang-Ⅱ in plasma and Ang-Ⅱ in tissues of mesenteric artery were detected in all the rats after 12 weeks of treatment. Results: The level of SBP after treatment in the QCHD group was lower than that in the model group ( P<0.01 ), but with no significant difference as compared with that in the Captopril group and the NJP group (P>0.05). After treatment, the plasma level of ET was lower and CGRP higher than those in the model group (both P<0.05), and also higher than those in the NJP and Captopril group (both P<0.05). As for the content of Ang- Ⅱ, in mesenteric arterial tissues, it was lower in the QCHD group than that in the model group ( P<0.05), but in plasma, it showed no significant difference between the two groups (P>0.05). Conclusion: QC has a satisfactory hypotensive action on SHR rats, and its mechanism may be associated with the regulation on plasma vasoactive peptide and regional renin-angiotensin system.

  9. 降钙素预防兔颞下颌关节创伤性骨关节病的实验研究%Experimental study of the effect of salmon calcitonin on post-traumatic osteoarthrosis

    Institute of Scientific and Technical Information of China (English)

    闫春歌; 张志光; 苏凯; 匡世军

    2011-01-01

    Objective: To study the effect of salmon calcitonin on post-traumatic osteoarthrosis in rabbit model.Methods: Post-traumatic osteoarthrosis model was created in 12 New Zealand rabbits.In the treatment group(n =6) salmon calcitonin at 3 μg/kg was given daily for 4 weeks.In the control group( n = 6) normal salin was used.Then the animals were sacrificed, the TMJs were examined by histopathological detections including HE and toluidine blue staining.Modified Mankin's score was used to evaluate the histological change.Results: The histological scores of the control group and treatment group were 9.1 ± 2.7 and 4.2 ± 1.3 respectively ( P < 0.05 ).Conclusion: Salmon calcitonin may be effective in the prevention of TMJ post-traumatic osteoarthrosis.%目的:探讨降钙素对颞下颌关节创伤性骨关节病的预防作用.方法:新西兰大白兔12 只制作颞下颌关节创伤性骨关节病模型,随机分为2 组:降钙素治疗组,对照组.切取TMJ,HE、甲苯胺蓝染色后,组织病理学观察,组织学评分采用改良的Mankin's计分方法.结果:对照组呈现骨关节病表现,治疗组见软骨修复现象.治疗组和对照组组织学评分分别为4.2±1.3、9.1±2.7(P<0.05).结论:降钙素能延缓外伤所致TMJ创伤性骨关节病的发生且明显降低软骨退变的程度.

  10. The Effect of Sodium Hyaluronate and Salmon Calcitonin in the Treatment of Postmenopausal Osteoporosis%阿仑膦酸钠与鲑鱼降钙素治疗绝经后骨质疏松症的效果

    Institute of Scientific and Technical Information of China (English)

    梁斌斌; 鞠传静

    2016-01-01

    目的:探究阿仑膦酸钠联合鲑鱼降钙素对治疗绝经后骨质疏松症的临床效果。方法根据我院2014年4月~2016年4月所收治的114例绝经后骨质疏松症患者的临床治疗资料,采用随机分组方式将患者分为对照组(使用阿仑膦酸钠和碳酸钙 D3片)和治疗组(在对照组基础上联合鲑鱼降钙素),每组57例,对比两种用药方式的治疗效果。结果对比两种药用方式下患者骨密度改善情况和疼痛感改善情况,治疗组优于对照组,差异有统计学意义(P <0.05)。两组患者均未出现明显的药物不良反应。结论相比于单纯使用阿仑膦酸钠,联合鲑鱼降钙素有利于提升绝经后骨质疏松症患者的骨密度和疼痛感,并且药物起效快、药效稳定、持久,并且无明显不良反应。%Objective To explore the clinical effect of the combination of sodium hyaluronate and salmon calcitonin in the treatment of postmenopausal osteoporosis. Methods From April 2014 to April 2016, 114 cases of postmenopausal osteoporosis in patients with clinical data, control group (using Sodium hyaluronate and calcium carbonate D3 tablets), treatment group (combined with salmon calcitonin), each group has 57 patients. Results The treatment group was significantly better than the control group, the results were statistically significant (P<0.05). There were no obvious adverse drug reactions in the two groups. Conclusion Compared with the simple use of sodium hyaluronate, combined with salmon calcitonin is beneficial to improve bone density and pain in postmenopausal osteoporosis patients.

  11. 鲑鱼降钙素对维持性血液透析患者血压的影响%The Effect of Salmon Calcitonin on Blood Pressure in Patients with Maintenance Hemodialysis

    Institute of Scientific and Technical Information of China (English)

    刘春秋; 李良志; 刘雷; 汤跃武; 史继红; 王军; 吴泽成; 何先红

    2013-01-01

    Objective:To observe the effect of salmon calcitonin on blood pressure in patients with maintenance hemodialysis. Methods:120 patients having long-term maintenance hemodialysis along with chronic renal failure were selected, and they were randomly divided into a control group (n=60) and a treatment group (n=60) by sortition. Patients in control group were treated according to conventional treatment drug. Based on the treatment in control group, salmon calcitonin injections were applied in the patients of treatment group.The changes of blood pressure and iPTH levels were observed before and after treatment.Results:Compared with the control group, diastolic blood pressure, systolic blood pressure and iPTH levels were significantly decreased in the treatment group (P<0.05), the rate of reaching the standard in blood pressure was significantly increased (x2=4.48,P=0.034).Conclusion:The application of salmon calcitonin in maintenance hemodialysis patients can lower iPTH levels in blood and help to control blood pressure.%  目的:观察鲑鱼降钙素对维持性血液透析患者血压的影响。方法:选择长期维持血液透析慢性肾衰患者120例,按抽签方式随机分为对照组和治疗组,各60例,对照组按常规给予治疗药物,治疗组在对照组治疗基础上应用鲑鱼降钙素注射液,观察治疗前后血压、血iPTH水平的变化。结果:与对照组比较,治疗组舒张压、收缩压、血iPTH水平均显著下降(P<0.05),血压达标率显著提高(x2=4.48,P=0.034)。结论:维持性血液透析患者应用鲑鱼降钙素能降低血iPTH水平,有助于血压的控制。

  12. Acute and Subacute Toxicity of Recombinant Saccharomyces cerevisiae Expressing Salmon Calcitonin%多拷贝表达转鲑鱼降钙素基因酵母的急性、亚急性毒性

    Institute of Scientific and Technical Information of China (English)

    王鹏; 姜勇; 田敬云; 马健; 张学成; 路兴波

    2012-01-01

    口服转鲑鱼降钙素基因酵母为鲑鱼降钙素的应用开辟了一条新的途径.为评价转鲑鱼降钙素基因酵母的安全性,将转基因酵母分别灌胃昆明种小鼠和Wistar大鼠进行急性毒性实验(7d)、亚急性毒性实验(8周).急性毒件实验结果表明灌喂转基因酵母对小鼠无致死效应(LD50>10000mg/kg);亚急性毒性实验中高(2.0g/kg)、低(0.5g/kg)剂量组动物的一般状况、体重、主要脏器系数、血液学指标及血液生化指标与各对照组比较,均未见明显差异(P>0.05),组织病理切片检查未发现病理性变化.实验结果说明转鲑鱼降钙素基因酵母不会对实验动物造成不良影响,是安全无毒的.%Oral administration recombinant Saccharomyces cerevisiae expressing salmon calcitonin made a new method for salmon calcitonin delivery system. Transgenic S. cerevisiae was evaluated for its acute (7 days) and subacute toxicity (8 weeks) by the oral route in KM mouse and Wistar rats respectively. In the acute toxicity test, every group did not produce any hazardous symptoms or deaths (LD50> 10 000 mg/kg). The subacute treatment with transgenic 5. Cerevisiae (2.0 and 0.5 g/ kg) failed to change body weight gain, food and water consumption. Organ/weight ratios, haematological and biochemical indices analysis showed no significant differences (P > 0.05) in any of the parameters examined. There was no pathological change observed in slice. These results suggested that recombinant S. cerevisiae expressing salmon calcitonin had no negative influences on the tested animal. It was safe and nontoxic. Fig 3, Tab 3, Ref 16

  13. 鲑鱼降钙素(密盖息)治疗老年骨质疏松症的疗效分析%Efficacy of Salmon Calcitonin(Miacalcic)in Treatment of Senile Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    伍先明; 吴俊

    2013-01-01

    Objective:To explore salmon calcitonin(dense cover interest)on the treatment of senile osteoporosis.Method:Selected the elderly patients with clinical symptoms of osteoporosis and 72 cases diagnosed by X-ray absorptiometry(DEXA)determination,and were randomly divided into observation group and control group. The observation group were 37 cases,be the intramuscular injection of salmon calcitonin,1-4 weeks,once every other day,50 U intramuscular injection;the first 5-12 weeks,weekly,50U intramuscular injection. Oral Caltrate-D,one each,2 times a day. Control group,35 patients treated with oral equal Caltrate-D films,one each,2 times a day.The treatment lasted 12 weeks. Result:After 12 weeks of treatment, as the observation of salmon calcitonin group than in the control group bone pain and disease remission(97.2% and 42.8%),the treatment effect(P<0.01). The observation group BMD(0.948 ± 0.261)g/cm2 compared with before treatment(0.834 ± 0.223)g/cm2,was increased(P<0.05);control group no significant change in BMD.Conclusion:The application of salmon calcitonin(dense cover interest)and calcium can alleviate the clinical symptoms of senile osteoporosis and increase the role of the lumbar spine BMD.%  目的:探讨鲑鱼降钙素(密盖息)对老年骨质疏松的治疗效果.方法:选取通过 X 线骨密度仪(DEXA)测定确诊为骨质疏松且有临床症状的老年患者72例,随机分为观察组和对照组.其中观察组患者给予鲑鱼降钙素肌肉注射,第1~4周,隔天1次,50 U 肌肉注射;第5~12周,每周1次,50 U 肌肉注射.同时口服钙尔奇-D,每次1片,2次/d.对照组患者给予单纯口服同等钙尔奇-D 片,每次1片,2次/d.两组疗程均为12周.结果:治疗12周后比较,予以鲑鱼降钙素的观察组较对照组骨痛症缓解(两组缓解率分别为97.2%和42.8%)效果明显(P<0.01).观察组 BMD(0.948±0.261)g/cm2较治疗前(0.834±0.223)g/cm2有所升高(P<0.05);对照组 BMD 无明显变化.结论:鲑

  14. Effect of Busheng Zhuanggu Formula and Salmon Calcitonin on Elderly Osteoporosis%补肾壮骨方联合鲑鱼降钙素治疗老年骨质疏松症临床观察

    Institute of Scientific and Technical Information of China (English)

    李德梅; 蔡莉莉; 李丽娜; 李敬会; 夏忠诚; 余武

    2011-01-01

    Objective To study the clinical effect of Busheng Zhuanggu formula and salmon calcitonin on elderly osteoporosis.Methods One hundred cases of elderly with osteoporosis were randomly divided into trial group and control group.Patients in control group were treated with calcitonin and calcium supplement with Vitamine-D Chewable Tablets, and patients in trial group were treated with Busheng Zhuanggu formula and salmon calcitonin additionally.The bone mineral density (BMD) and BGP, TRAP,HYP of two groups before and after treatment were observed.Results In treatment group and in control group, BMD of lumber vertebrae (L2-4) and neck of femur increased significantly after three month treatment compared with control group (P >0.05), but no significant change in the region of Wards.The remission rate of osteodynia was 98.60% in trial group and 71.42% in control groups (P<0.05).The level of serum BGP increased in trial group and the ratio of urinary HYP/Cr decreased, with significant difference between the two groups (P <0.05).Conclusion The combining treatment of salmon calcitonin and Busheng Zhuanggu formula on elderly osteoporosis can relieve the osteodynia and increase bone mass.%目的 探讨补肾壮骨方联合鲑鱼降钙素对老年骨质疏松症的临床疗效.方法 选择100例老年骨质疏松症患者,随机分为观察组和对照组.2 组均服用维D钙咀嚼片,对照组静脉点滴骨肽针,观察组在对照组治疗基石出上肌注鲑鱼降钙素针、口服补肾壮骨方,疗程均为3个月.观察2组治疗前后骨密度及骨钙素(BGP)、血抗酒石酸酸性磷酸酶(TRAP)、尿羟脯氨酸(HYP)等指标的变化.结果 治疗3个月后,2组腰推、股骨预部的骨密度较治疗前均有升高,而治疗组升高更明显,2组比较差异有统计学意义(P<0.05),Ward:区骨密度无显著性改变;观察组骨痛总有效率为98.60%,对照组为71.42%(P<0.05);2组血BGP水平治疗后呈增高的改变,血TRAP水平和尿HYP

  15. Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guangshun Zheng; Yongjie Yang; Xiubin Fang

    2006-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied.OBJECTIVE:To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion.DESIGN: Randomized controlled animal study.SETTING:Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University.MATERIALS:A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA),and NGF (1 × 106 U/L, 0.5 mL, Siweite Company, Dalian).METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to duly 20055. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1 ×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham

  16. Application of calcitonin for the treatment of unstable intertrochanteric fractures in elderly patients%降钙素在老年不稳定型股骨转子间骨折应用

    Institute of Scientific and Technical Information of China (English)

    陈宝; 陈国俊; 龚遂良; 黄成龙; 范顺武

    2014-01-01

    Objective To compare the clinical outcomes between proximal femoral nail antirotation (PFNA) combined with salmon calcitonin and PFNA only for the treatment of unstable intertrochanteric fractures in elderly patients.Methods From January 2009 to December 2011,120 elderly patients with intertrochanteric fracture were randomly divided into two groups:calcitonin group and control group.Patients in calcitonin group were treated with PFNA combined with salmon calcitonin,while patients in control group were treated with PFNA only.According to Evans-Jensen classification,60 patients in calcitonin group (28 males and 32 females,with an average age of 75.1 years) were divided into 20 cases of type Ⅱ A,32 cases of type Ⅱ B and 8 type Ⅲ.Sixty patients in control group (27 males and 33 females,with an average age of 74.9 years) were divided into 22 cases of type Ⅱ A,32 cases of type Ⅱ B and 6 type Ⅲ.Bone healing was assessed with X-ray and bone mineral density (BMD) was measured by dual energy X-ray absorptiometry.Harris hip and SF-12 score,complications,adverse effect of salmon calcitonin and subsequent fragility fractures were evaluated postoperatively.Results One-hundred and thirteen patients were followed up for at least 2 years.In 6 months after surgery,there were 4 cases of delayed healing in control group.However,all fractures were healed in 12 months after surgery.No significant difference was found between the two groups in BMD preoperatively.The changes in BMD were significantly different between the two groups in 6 months,1 year and 2 years after surgery.No significant difference was found between the two groups in Harris hip and 1-year SF-12 score while the 2-year SF-12 score was significantly different between the two groups.There was 1 patient in calcitonin group who suffered from subsequent fragility fracture in 3 months after surgery,while there was 6 patients in control group during 13 to 23 months postoperatively.Conclusion PFNA combined with

  17. Efficacy of Salmon Calcitonin plus Erxian Decoction (EXD)for Osteoporosis in Postmenopausal Women :A Clinical Observation%二仙汤合鲑鱼降钙素治疗绝经后骨质疏松症的临床观察

    Institute of Scientific and Technical Information of China (English)

    朱庆翱; 顾敏琪

    2012-01-01

    目的:观察二仙汤合鲑鱼降钙素对绝经后骨质疏松症患者临床疗效及骨代谢生化指标的影响.方法:采用随机数字表法将70例绝经后骨质疏松症患者分为治疗组和对照组,每组35例,治疗组给予二仙汤合鲑鱼降钙素治疗.对照组不予中药,余同治疗组.疗程12周,观察两组治疗前后主要症状积分改变、骨密度T值及骨代谢生化指标的变化.结果:治疗组总有效率为94.29%,对照组总有效率77.14%.两纽比较,差异有统计学意义(P<0.05).两组治疗后主要症状积分比较,差异均有统计学意义(P <0.05或P<0.01).说明在改善患者的诸多躯体症状上,治疗组优于对照组.两组治疗后骨密度值比较,差异有统计学意义(P<0.05),说明治疗组提高骨密度效果优于对照组.治疗组可提高碱性磷酸酶、雌二醇、骨钙素、降钙素水平,作用优于对照组(P<0.05或P<0.01).结论:二仙汤合鲑鱼降钙素临床疗效优于单纯使用鲑鱼降钙素,是防治绝经后骨质疏松症的有效方法,值得推广.%Objective:To observe the effects of Erxian Decoction and salmon calcitonin on postmenopausal osteoporosis patients with clinical and biochemical markers of bone metabolism effect. Methods:JO cases of postmenopausal osteoporosis were randomly divided into treatment group(35 cases) ,in which Erxian Decoction and salmon calcitonin were used as the treatment. 35 cases of the control group were only given salmon calcitonin treatment. 12 weeks was a treatment course. Two groups were observed before and after treatment of pain symptoms improve,T value of BMD and bone metabolism biochemical changes. Results;The total effective rate in the treatment group was 94. 29% ,in the control group was 77. 14%. There was significant difference between two groups(P <0. 05). Treatment group patients with bone pain,low back pain symptoms were improved, showing a significant difference between two groups (P < 0. 05

  18. The protective effect of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats%大鼠脑缺血再灌注后降钙素基因相关肽对受损胃黏膜的保护作用

    Institute of Scientific and Technical Information of China (English)

    冯国营; 许晓博; 王迁

    2009-01-01

    @@ The purpose of the present study is to investigate the protective effect of calcitonin gene-related pepfide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting.

  19. Effect of Salmon Calcitonin in the Treatment of Elderly Patients with Os-teoporosis%鲑鱼降钙素治疗老年骨质疏松患者的效果分析

    Institute of Scientific and Technical Information of China (English)

    葛彪

    2016-01-01

    Objective To explore the effect of salmon calcitonin in the treatment of elderly patients with osteoporosis. Methods In our hospital from February 2015 to March 2014, 62 cases of elderly patients with osteoporosis were ran-domly divided into observation group and control group, each of 31 cases. The observation group was treated with salmon calcitonin, and the control group was treated with calcium agent, and the clinical effect of the two groups was compared. Results In the observation group, 18 cases were markedly effective, 12 cases were effective, the total effec-tive rate was 97.77%;the control group was markedly effective in 11 cases, effective in 14 cases, the total effective rate was 80.65%; the comparison between groups, P<0.05. Before and after treatment, the two groups of lumbar BMD com-parison, two groups of BMD have a certain change, and the observation group change is more obvious, and is better than the control group and the control group, the difference was significant, P<0.05. Conclusion The elderly osteoporo-sis by salmon calcitonin treatment, clinical effect is better, can effectively improve the clinical symptoms of patients, it is worthy of clinical application and promotion.%目的:探究鲑鱼降钙素治疗老年骨质疏松患者的效果。方法选取该院2014年3月—2015年2月收治的62例老年骨质疏松患者,随机分成观察组和对照组,各31例。观察组给予鲑鱼降钙素治疗,对照组通过钙剂药物治疗,对比两组临床疗效。结果观察组显效18例,有效12例,治疗总有效率97.77%;对照组显效11例,有效14例,治疗总有效率80.65%;组间比较,差异有统计学意义,P<0.05。治疗前﹑后,两组腰椎BMD比较,两组BMD均有一定改变,且观察组变化更加明显,且优于对照组和对照组,差异有统计学意义,P<0.05。结论老年骨质疏松经鲑鱼降钙素治疗,临床效果较好,同时可有效改善患者的临床症状,值得临床深入推广和应用。

  20. 鲑鱼降钙素治疗老年糖尿病并发骨质疏松的效果分析%Efficacy analysis of salmon calcitonin in the treatment of senile diabetes complicated with osteoporosis

    Institute of Scientific and Technical Information of China (English)

    李洪昌; 廖浩峰; 邓颖玉

    2015-01-01

    Objective To investigate the efficacy of salmon calcitonin in the treatment of senile diabetes complicated with osteoporosis. Methods 70 patients with senile diabetes complicated with osteoporosis were selected as research objects and randomly divided into control group and observation group.Calcium carbonate D3 tablet was used in control group,calcium carbonate D3 tablet combined with salmon calcitonin were applied in observation group.The pain degree, effect and the level of serum BMD,BGP,AKP and PTH in two groups were compared.The adverse reaction in two groups were recorded. Results After treatment,the pain degree of observation group was significantly improved,and significantly better than that of control group (P<0.05).After treatment,the level of BMD,BGP in observation group was significantly higher than that in control group and before treatment respectively(P<0.05).After treatment,the level of AKP,PTH in ob-servation group was significantly lower than in control group and before treatment respectively (P<0.05).Total effective rate of observation group was 94.3%,significantly higher than that of control group(77.1%)(P<0.05).The incidence rate of adverse reaction in observation group was significantly lower than that in control group(P<0.05). Conclusion The clini-cal efficacy of salmon calcitonin in the treatment of senile diabetes complicated with osteoporosis is significant.%目的:探讨鲑鱼降钙素治疗老年糖尿病并发骨质疏松的效果。方法选取70例老年糖尿病并发骨质疏松患者为研究对象,随机分为对照组和观察组,对照组给予碳酸钙D3片治疗,观察组采用碳酸钙D3片联合鲑鱼降钙素治疗,比较两组的疼痛程度、治疗效果及血清BMD、BGP、AKP及PTH含量,记录两组不良反应发生情况。结果观察组治疗后的疼痛程度明显改善,且明显好于对照组(P<0.05);观察组治疗后的BMD、BGP水平高于对照组及治疗前(P<0.05);观察组治

  1. 鲑鱼降钙素促进老年转子间骨折愈合的疗效观察%Efficacy Observation of Salmon Calcitonin for Femoral Intertrochanteric Fractures Healing in Elderly Patients

    Institute of Scientific and Technical Information of China (English)

    谭美云; 郭杏; 税巍; 王远辉; 张忠杰

    2011-01-01

    目的:观察鲑鱼降钙素促进老年转子问骨折愈合的疗效.方法:将40例老年患者随机分为2组:治疗组20例,肌肉注射鲑鱼降钙素;对照组20例,在相同的部位肌肉注射等量注射用生理盐水.自术后第1天开始,2组均连续用药3个月.用药后的第1、3个月复查X线片,观察骨痂生长情况.治疗前和治疗后3个月检测患者腰椎(L4)骨密度(BMD)及血清钙、磷、碱性磷酸酶等浓度.结果:所有患者均得到随访.术后第1、3个月x线评估发现,治疗组比同时期对照组的骨痂生成量多.治疗后3个月,治疗组腰椎(L4)BMD明显高于对照组(P0.05),治疗组碱性磷酸酶明显高于对照组(P<0.05).治疗组1例出现恶心、呕吐等胃肠道症状,2例出现面颈部潮红.结论:鲑鱼降钙素能显著促进老年转子间骨折的愈合.%OBJECTIVE: To observe the therapeutic efficacy of salmon calcitonin for femoral intertrochanteric fractures healing in elderly patients. METHODS: A total of 40 elderly patients with femoral intertrochanteric fractures were randomly divided into 2 groups. 20 cases in treatment group received intramuscular injection of salmon calcitonin and 20 cases in control group received equal dose of normal saline at the same site. Both groups were given medicine after operation for 3 months. The X-ray plate of 2 groups was examined at 1 and 3 months after treatment to investigate the condition of bony callus. The BMD of the lumbar spine at LA, the concentration of serum calcium, serum phosphorus and alkaline phosphate were measured before treament and 3 months after treatment. RESULTS: All patients were followed up. The X-ray plate showed that the bony callus in treatment group was more abundant than in control group at 1 and 3 months after treatment. 3 months after treatment, the BMD of the lumbar spine at L4 in treatment group was significantly higher than in control group (P<0.05). The concentration of serum calcium in treatment group was

  2. 鲑鱼降钙素治疗脊髓损伤致骨质疏松症的效果%Effect of Salmon Calcitonin on Osteoporosis Induced by Spinal Cord Injury

    Institute of Scientific and Technical Information of China (English)

    李军; 杨德刚; 陈亮; 杨明亮; 杜良杰; 刘宏炜; 周天健; 董学超; 范维娇; 郭韵; 王冲; 高峰

    2015-01-01

    Objective To explore the effect of salmon calcitonin on osteoporosis induced by spinal cord injury. Methods 100 patients with osteoporosis induced by spinal cord injury from September 2011 to September 2014 in our department were included. They were ran-domly divided into control group (n=50) and observation group (n=50). The control group received vitamin D3 only, while the observation group received vitamin D3 combined with salmon calcitonin on the basis of rehabilitation physiotherapy, for 6 months. Visual Analogue Scale (VAS) of pain was evaluated in different periods. The bone mineral density (BMD) of lumbar spine and femoral neck, the parathyroid hormone (PTH), bone gla protein (BGP) and 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3) were tested and recorded. Results The VAS score was lower in the observation group than in the control group 1, 2, 3 and 6 months after treatment (P<0.001). The BMD of lumbar spine and femoral neck was significantly higher, the PTH and BGP were significantly lower and the 1,25-(OH)2D3 was significantly higher in the obser-vation group than in the control group after treatment (P<0.001). Conclusion Combination of salmon calcitonin can effectively reduce the bone pain and improve the BMD in patients with osteoporosis induced by spinal cord injury.%目的:观察鲑鱼降钙素治疗脊髓损伤所致骨质疏松症的临床效果。方法2011年9月~2014年9月本科收治的脊髓损伤致骨质疏松症患者100例,按随机数字表法将其分为对照组(n=50)和观察组(n=50)。对照组在康复理疗的基础上单纯给予维生素D3,观察组则在康复理疗的基础上给予维生素D3联合鲑鱼降钙素治疗,共6个月。测定治疗不同时间段患者疼痛视觉模拟评分(VAS),腰椎及股骨颈骨密度(BMD)及甲状旁腺素(PTH)、骨钙素(BGP)、1,25-双羟维生素D3[1,25-(OH)2D3]等生化指标的变化情况。结果治疗1个月、2个月、3个月及6个月后观察组患者VAS

  3. A influência da calcitonina sintética de salmão na cicatrização cutânea de ratos Influence of the synthetic salmon calcitonin in cutaneous wound healing of the rats

    Directory of Open Access Journals (Sweden)

    José Neiva Eulálio

    2007-08-01

    Full Text Available OBJETIVO: O presente trabalho tem como objetivo investigar a influência da calcitonina sintética do salmão no processo cicatricial da pele da região dorsal em ratos, analisando parâmetros bioquímicos, biomecânicos e histológicos, e suas possíveis interrelações. MÉTODO: Setenta e dois (72 ratos machos adultos foram submetidos, sob anestesia geral inalatória a uma incisão linear na pele que foi, subseqüentemente, suturada. Metade dos ratos (grupo teste foi tratada no pós-operatório com calcitonina sintética do salmão, e a outra metade, sem tratamento, constituiu o grupo controle. Os animais, em pares de nove ratos cada (teste e controle, foram sacrificados no 5º, 10º, 15º e 20º dias pós-operatório para a remoção dos fragmentos de pele com cicatriz para as análises bioquímicas, biomecânicas e histológicas. Utilizou-se o teste "t" de Student para a comparação de médias de amostras independentes e o teste de correlação de Pearson para verificar o grau de associação entre as médias das variáveis. RESULTADOS: A calcitonina sintética de salmão acelerou o processo cicatricial da pele, mas não de maneira linear e constante. Em comparação com os animais não-tratados, houve aumento significativo tanto do conteúdo de hidroxiprolina nas fases de proliferação inicial e tardia da cicatrização, quanto da carga máxima de ruptura na fase de proliferação tardia. Os resultados histológicos corroboram os resultados bioquímicos e biomecânicos, sugerindo uma correlação entre conteúdo de colágeno, resistência à tração e histologia da cicatriz. CONCLUSÃO: A calcitonina sintética de salmão acelerou o processo cicatricial da pele, modificando significativamente o conteúdo de colágeno e a carga máxima de ruptura, mas não de maneira linear e constante.BACKGROUND: The aim of the present study was to investigate the influence of synthetic salmon calcitonin on wound healing in dorsal skin of rats

  4. Inhibition of calcitonin gene-related peptide and insulin-like growth factor: a potential new therapeutic strategy to reduce bone pain in bone metastases of breast cancer%抑制降钙基因相关肽和胰岛素样生长因子:一种减轻乳腺癌骨转移患者骨痛的新策略

    Institute of Scientific and Technical Information of China (English)

    梁燕

    2010-01-01

    @@ 2009年圣·安东尼奥会议上,Teruhisa Sakurai等作了题名为"Inhibition of calcitonin gene-related peptide and insulin-like growth factor:a potential new therapeutic strategy to reduce bone pain in bone metastases of breastcancer"的报告.

  5. 密骨灵与密钙息治疗肿瘤疼痛的临床对照研究%Comparison of imported and domestic calcitonin salmon in treatment of cancer pain

    Institute of Scientific and Technical Information of China (English)

    张力; 王树兰; 李龙芸; 刘倩; 原永平; 吴梅娜

    2001-01-01

    Objective:To observe the efficacy nd safety of dome stic calcitonin salmon(Miguling)in comparison with imported one(Miacalcic)in tre tment of pains of bone-metastatic cancer.Methods:71 patients with pains of bone-metastatic cancer were randomly divided to receive Miguling (n =51) or Miacalcic(n=20)and observed their efficacy.Results:T he total effective rates in Miguling and Miacalcic group are simillar,and no sig nificant difference(P<0.05) was observed.Conclusions:The domes tic calcitonin salmon(Miguling)is an effective agent for treatment of pains of b one-metastic cancer.%目的:观察国产人工合成鲑鱼降钙素注射液对各种恶 性肿 瘤骨转移性疼痛的止疼效果及治疗安全性,并与进口同类产品密钙息进行对照观察。方法:71例患者分成密骨灵组51例,密钙息组20例。两组给药方法相同,即第1周每天、第2周隔日、第3周周末皮下注射50~100IU。结果:密 骨灵组51例中完全缓解13.7%;部分缓解56.9%;总有效率70.6%。与进口密钙息疗效一致( P<0.05),且不良反应轻微。结论:密骨灵治疗轻、中、重度肿瘤 骨转移所致的疼痛有一定疗效且较安全。

  6. Safety Evaluation of Recombinant Sacchromyces cerevisiae Expressing Salmon Calcitonin by Orally Administration%口服转鲑鱼降钙素基因酵母的安全性评价

    Institute of Scientific and Technical Information of China (English)

    陈云松; 张学成; 姜勇; 高岩; 黄维清

    2009-01-01

    To evaluate the toxicological safety of recombinant Sacchromyces cerevisiae expressing salmon calcitonin,tests included acute toxicity test,micronucleus test,sperm shape abnormality test,traditional teratogenicity test and 30 days feeding test were performed.Results showed oral LD_(50) was higher than 10.0 g/kg both in male and female mice.Micronucleus test and Sperm shape abnormality test were negative.There was no maternal toxicity or embryotoxicity in teratogeniccity test.No significant toxicity was detected in 30 days feeding test.Conclusion could be drawn that recombinant Saccharomyces cerevisiae expressing salmon calcitonin has no negative influences on the animal,which proves that it is safe and nontoxic.%以小鼠为实验对象对表达鲑鱼降钙素的转基因酵母进行了毒理学实验,包括急性毒性实验、遗传毒性实验(小鼠骨髓微核实验、小鼠精子畸形实验)、传统致畸实验和大鼠30 d喂养实验.结果表明,急性毒性实验显示LD50>10.0 g/kg,属于实际无毒物质;遗传毒性实验结果均为阴性,显示无致突变性;致畸实验结果表明转鲑鱼降钙素基因酵母对小鼠不会产生母体毒性,对小鼠胚胎发育无影响且无致畸作用;30 d喂养实验中各项检测指标均无显著差异(p>0.05),组织病理切片检查未发现病理性变化.本文的结论是口服转鲑鱼降钙素基因酵母未对实验动物造成不良影响,是安全无毒的.

  7. Effects of the prototype serotonin 5-HT(1B/1D) receptor agonist sumatriptan and the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) on myocardial reactive hyperemic response in conscious dogs.

    Science.gov (United States)

    Lynch, Joseph J; Shen, You-Tang; Pittman, Tamara J; Anderson, Kenneth D; Koblan, Kenneth S; Gould, Robert J; Regan, Christopher P; Kane, Stefanie A

    2009-11-25

    The triptans, serotonin 5-HT(1B/1D) receptor agonists exemplified by sumatriptan, are a mainstay migraine therapy but have class labeling contraindicating their use in patients with coronary artery disease. Triptans constrict human coronary artery in vitro, and there are case reports of myocardial infarction in patients using sumatriptan. However, preclinical studies with sumatriptan in normal dogs have failed to demonstrate effects on resting coronary flow. Calcitonin gene-related peptide (CGRP) receptor antagonism, exemplified by the prototype CGRP receptor antagonist peptide CGRP(8-37), is a new antimigraine mechanism which also has been reported to have no effect on coronary flow in normal, non-stressed animals. The goal of the present studies was to compare the effects of sumatriptan (10microg/kg/min i.v.) and CGRP(8-37) (30microg/kg/min i.v.) on systemic and coronary hemodynamics in conscious dogs under resting conditions and during myocardial reactive hyperemia following a brief 15s of coronary artery occlusion. Neither CGRP(8-37) nor sumatriptan affected resting coronary flow. However, whereas CGRP(8-37) had no effect on myocardial reactive hyperemic response, sumatriptan reduced peak reactive hyperemic coronary artery blood flow (baseline vs treatment: 75.4+/-12.7 vs 60.0+/-10.3ml/min, Ptriptan effects on coronary vascular function.

  8. Effects of alpha-calcitonin gene-related peptide on osteoprotegerin and receptor activator of nuclear factor-κB ligand expression in MG-63 osteoblast-like cells exposed to polyethylene particles

    Directory of Open Access Journals (Sweden)

    Kauther Max D

    2010-11-01

    Full Text Available Abstract Background Recent studies demonstrated an impact of the nervous system on particle-induced osteolysis, the major cause of aseptic loosening of joint replacements. Methods In this study of MG-63 osteoblast-like cells we analyzed the influence of ultra-high molecular weight polyethylene (UHMWPE particles and the neurotransmitter alpha-calcitonin gene-related peptide (CGRP on the osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factorκB (OPG/RANKL/RANK system. MG-63 cells were stimulated by different UHMWPE particle concentrations (1:100, 1:500 and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M. RANKL and OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. Results Increasing particle concentrations caused an up-regulation of RANKL after 72 hours. Alpha-CGRP showed a dose-independent depressive effect on particle-induced expression of RANKL mRNA in both cell-particle ratios. RANKL gene transcripts were significantly (P -7 M lead to an up-regulation of OPG protein. Conclusion In conclusion, a possible osteoprotective influence of the neurotransmitter alpha-CGRP on particle stimulated osteoblast-like cells could be shown. Alpha-CGRP might be important for bone metabolism under conditions of particle-induced osteolysis.

  9. Salmon calcitonin combined with ossification in three alcohol treatment of renal osteopathy%鲑鱼降钙素结合骨化三醇治疗肾性骨病疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨静; 张江淮; 吴永贵; 胡淑荣

    2013-01-01

    Objective:To observe the effects of salmon calcitonin combined ossification in three alcohol for treatment of renal osteodystrophy (renal osteopathy) effect. Methods:66 cases of patients with renal osteodystrophy were randomly divided into treatment group and control group, were treated with the basis of disease treatment, the treatment group added with salmon calcitonin (3 times 20 u, subcutaneous injection, once a week (with conventional hemodialysis), at the same time plus oral ossification in three alcohol treatment (0.25-1.0ug/D);control group with salmon calcitonin, parathyroid hormone in blood were detected before treatment and 3, 6, and 12 months (PTH), serum calcium, serum phosphorus level and lumbar pain, and the record level (visual analogue scale, VAS) and adverse reaction. Results:in the control group before treatment, serum calcium, serum phosphorus and PTH were 2.10 ± 0.28, 2.82 ± 0.34, 868.50 ± 125.57, after treatment were 2.34 ± 0.23, 2.23 ± 0.23 and 723.39 ± 117.73;the treatment group before treatment of parathyroid hormone (PTH), serum calcium, serum phosphorus level of 2.15 ± 0.40, 2.78 ± 0.45 、891.45 ± 124.73, after treatment were 2.78 ± 0.46, 2.12 ± 0.21, 610.57 ± 124.12, before and after the treatment, the difference was statistical y significant (P<0.05), the treatment group improved more obviously (P<0.05). Conclusion:the application of salmon calcitonin and combined with ossification in three alcohol can effectively reduce MHD in patients with bone loss in patients with renal osteodystrophy, decrease the level of PTH, improve the clinical symptomsand no obvious adverse reaction. It is worthy of clinical application.%目的:观察鲑鱼降钙素联合骨化三醇治疗肾性骨病(renal osteopathy)的疗效。方法:对66例肾性骨病患者随机分为治疗组和对照组,均予以治疗基础疾病,治疗组加用鲑鱼降钙素(20 u,皮下注射,每周3次(常规血液透析时使用),同时

  10. Treatment on osteopenia of maintenance hemodialysis patients with salmon calcitonin%鲑鱼降钙素治疗维持性血液透析骨量减少的患者

    Institute of Scientific and Technical Information of China (English)

    张东亮; 尹道馨; 郭王; 林雅慧; 刘文虎

    2008-01-01

    Objective To study the effect of long-term salmon calcitonin on bone mineral density (BMD), bone metabolism biochemical indicators and subjective score of bone pain in maintenance hemedialysis (MHD) patients with osteopenia. Methods Thirty-four MHD patients diagnosed as osteopenia by dual-energy X-ray absorptiometry (DXEA) were enrolled in this study. All the patients were treated with hypodermic injection of salmon calcitonin (50 U, thrice a week) for 12 months. The detecting parameters were as follows: BMD with DEXA in lumbar spine (L1-L4), femoral neck, troch, inter, and Ward's triangle before and after the study;serum bone metabolism biochemical indicators before and 6 and 12 months after the study;subjective scores of bone pain before and 1, 6, and 12 months after the study. Results Thirty-two patients were followed-up successfully. As compared to BMD parameters before study, the total T-score (-1.98± 2.20 vs 1.26±1.88, P=0.009) and total Z-score (-0.90±2.15 vs 0.08±2.05, P=0.002) of lumbar spine, the total T-score (-1.72±1.53 vs 1.06±1.58, P=0.016) and totle Z-score (-0.66±0.80 vs 0.08±1.08, P=0.029) of hip, the T-score of L3 (-2.02±2.51 vs 1.24±2.02, P=0.033), the Z-score of L2 (-0.44±1.82 vs 0.06±1.63, P=0.016), the Z-score of femoral troch (-0.65±1.11 vs 0.48±1.12, P=0.034) and the Z-score of inter (-0.58±0.94 vs 0.02±1.12, P=0.006) were increased significantly after study. But there were no significant differences in other examined regions and serum biochemical parameters. The subjective scores of bone pain were decreased rapidly for 41.7% after 1 month (P<0.01) and 76.6% after 6 months (P<0.01). The subjective score of bone pain after 12 months was similar to 6 months. The side effects of salmon calcitonin included nausea and vomitting in 5 cases (14.71%, 5/34), dizziness, blushing and flustered in 1 case respectively (3.13%,1/32). Conclusions Long-term hypodermic injection of salmon calcitonin can improve BMD and bone pain for MHD

  11. Effect of calcitonin on the expression of collagen gene during the healing process of osteoporotic fractures%降钙素对骨质疏松性骨折修复过程胶原基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    肖强; 刘静莉; 漆启华; 陆欢; 邓亮; 董谢平

    2013-01-01

    目的:探索降钙素对骨质疏松性骨折愈合过程中基质Ⅰ、Ⅱ、Ⅲ型胶原 mRNA表达的影响,阐明降钙素促进骨质疏松性骨折愈合的机制。方法选用96只2个月龄SD雌性大鼠,64只行双侧卵巢切除( OVX)后,随机平分为降钙素组和对照组,其余32只为假手术组;10周后所有大鼠在右侧桡骨下端制作1 mm骨缺损的骨折愈合模型。降钙素组从骨折术前1 w至术后8 w连续每天皮下注射鲑鱼降钙素2 IU/kg,另2组注射等量生理盐水。采用原位杂交技术分析7 d,14 d,28 d,56 d,4个时间、点降钙素对骨折修复过程中基质Ⅰ、Ⅱ、Ⅲ型胶原mRNA表达的影响。结果降钙素治疗下,骨基质Ⅰ型胶原mRNA表达的量与对照组比较有显著性差异,假手术组>降钙素组>对照组;Ⅲ型胶原mRNA的表达变化则与之相反。降钙素组软骨性骨痂向骨性骨痂转换时间较对照组缩短。结论降钙素能影响胶原mRNA的表达,明显促进骨质疏松性骨折的愈合。%Objective To investigate the effect of calcitonin on the mRNA expression of matrix type I , II, and III collagen during the healing process of osteoporotic fractures , and to illuminate the mechanism of calcitonin in promoting the healing of osteoporotic fractures.Methods A total of 96 2-month female SD rats were selected.Of which, 64 rats received bilateral ovariectomy (OVX), and they were randomly divided into calcitonin therapy group and control group .The other 32 rats were divided into sham operation group.Ten weeks later , all the rats made into fracture models with about 1mm width of the bone defect at the end of the right radius . Rats in the calcitonin therapy group received a subcutaneous injection of 2 IU/kg salmon calcitonin once a day from 1 week before the operation to 8 weeks after the operation .Rats in the other 2 groups were injected with same volume of normal saline .The effect of calcitonin on the m

  12. The application of salmon calcitonin in the treatment of osteoporotic vertebral compression fracture after kyphoplasty%鲑鱼降钙素在骨质疏松性椎体压缩骨折椎体后凸成形术后的应用

    Institute of Scientific and Technical Information of China (English)

    李钦亮; 王东岩; 刘艺; 储朝明; 陈金传; 陈鸣; 吴玉玲

    2012-01-01

    Objective To observe the amelioration of bone mineral density and low back pain after the use of salmon calcitonin in the treatment of osteoporotic vertebral compression fracture after kyphoplasty. Methods Seventy-nine patients with osteoporotic vertebral compression fracture to be treated with kyphoplasty were divided into 2 groups. Forty-four patients were chosen to form the salmon calcitonin group and treated with salmon calcitonin intramuscularly, 100 IU once a day, for three days after the operation. After that, they were treated with 50 IU salmon calcitonin once every other day for a month. This treatment was repeated in 1 month interval and continued for half a year. Meanwhile, oral vitamin D2 calcium phosphate was added. Thirty-five patients were chosen to form control group and treated with oral vitamin D2 calcium phosphate only for 6 months. BMD of the lumbar vertebrae 1-4 and the femoral neck of all patients in the two groups were measured before and after the treatment. The low back pain situation of the patients was observed. Results Six patients in the salmon calcitonin group developed facial flush and skin itching after muscular injection of salmon calcitonin and stopped the course. The rest 38 cases in the salmon calcitonin group and 35 cases in the control group were followed up. BMD of the lumbar spine and the femoral neck in the salmon calcitonin group increased significantly after the treatment ( P 0. 01) . No case in the salmon calcitonin group developed low back pain again. However, 7 cases in the control group developed low back pain again and vertebral compression fracture in other lumbar was confirmed with MRI. Conclusions The combination therapy of salmon calcitonin and calcium for the treatment of osteoporotic vertebral compression fracture after kyphoplasty can increase the bone mass of the patients and decrease the risk of fracture.%目的 观察鲑鱼降钙素对骨质疏松性椎体压缩骨折行椎体后凸成形术后骨密度及

  13. 鲑鱼降钙素围手术期应用对骨质疏松性股骨颈骨折镇痛效果的随机对照研究%Randomized controlled trials assessing the analgesic effect of perioperative application of salmon calcitonin on osteoporotic femoral neck fracture

    Institute of Scientific and Technical Information of China (English)

    李晓菲; 刘国伟; 朱玉磊; 张天龙; 朱明双

    2011-01-01

    目的 探讨骨质疏松症(OP)性股骨颈骨折疼痛的缓解作用.方法 将68例拟进行人工全髋置换术或人工半髋置换术的患者随机分为试验组和对照组,其中试验组34例,给予鲑鱼降钙素治疗;对照组34例,给予双氯芬酸钠双释放肠溶胶囊治疗.观察指标:术前第3天、术后第1天、术后第4天和术后第7天,两组患者均行VAS评分,以评估疼痛改善的情况.结果 术后第1天双氯芬酸钠双释放肠溶胶囊的止痛效果优于鲑鱼降钙素(P<0.05);至术后第7天,鲑鱼降钙素的止痛效果则优于双氯芬酸钠双释放肠溶胶囊(P<0.05).结论 在急性创伤反应期双氯芬酸钠双释放肠溶胶囊的止痛作用优于鲑鱼降钙素,随着创伤反应的减轻,其止痛作用有限,而鲑鱼降钙素的止痛作用逐渐显现,其止痛效果可能与改善OP性骨痛作用有关.%Objective To evaluate the pain relief effect of calcitonin salmon for osteoporotic femoral neck fractures in perioperative period ( preoperative three days to postoperative seven days ). Methods 68 patients who accepted total hip replacement ( THR ) or artificial half hip arthroplasty were randomly divided into trial group and control group. Trial group ( 34 patients ) were given calcitonin salmon and control group ( 34 patients ) were given Diclofenac sodium double release Intestine-sol Capsule. Observing indexes : on the lst day before operation and, respectively on the 1st, 4th and 7th day after the operation, both groups used the scores of VAS to estimate the pain improvement. Results The pain relief effectiveness of Diclofenac sodium double release Intestine-sol Capsule was better than calcitonin salmon at the 1st day after the operation ( P< 0. 05 ). On the 7th day after the operation calcitonin salmon was superior to Diclofenac sodium double release Intestine-sol Capsule ( P < 0. 05 ). Conclusions During the period of the acute traumatic reaction, the pain relief effect of Diclofenac

  14. Evaluation of therapeutic effect of salmon calcitonin, alfacalcidol, calcium carbonate in the treatment of 40 cases of osteoporotic intertrochanteric fractures%鲑降钙素、阿法骨化醇、碳酸钙联合应用治疗骨质疏松性股骨粗隆间骨折40例疗效分析

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    王思成; 刘祥飞; 吴献民; 何金国; 张友忠; 杨国庆

    2013-01-01

      目的:比较鲑降钙素、阿法骨化醇、碳酸钙联合应用与单用鲑降钙素治疗骨质疏松性股骨粗隆间骨折的临床疗效。方法:将80例行闭合复位PFNA内固定术治疗的骨质疏松性股骨粗隆间骨折患者,随机分为实验组及对照组。分别给予肌注鲑降钙素+口服阿法骨化醇和碳酸钙和单纯肌注鲑降钙素。治疗6个月及1年后测定骨密度值及观察骨折愈合时间并进行比较。结果:实验组治疗6个月和1年后腰椎和股骨颈,Ward三角及大转子4个部位BMD较对照组均显著上升(P<0.05)。实验组与对照组比较,骨折愈合时间有显著性差异。结论:闭合复位PFNA内固定术治疗骨质疏松性股骨粗隆间骨折后,给予肌注鲑降钙素+口服阿法骨化醇和钙剂可显著提高患者的骨密度,缩短骨折的愈合时间,明显优于单纯给予肌注鲑降钙素的疗效。%ABSTRACT Objective:To study the clinical efficacy of a monotherapy of salmon calcitonin or a combination therapy of salmon calcitonin with alfacalcidol and calcium carbonate on osteoporotic intertrochanteric fracture. Methods:Eighty patients with osteoporotic intertrochanteric fractures who received a reduction and internal fixation with PFNA were randomly divided into either experimental group or control one. Patients in experimental group were administrated with intramuscular salmon calcitonin plus oral alfacalcidol and calcium carbonate while only intramuscular salmon calcitonin was given in control group. BMD was measured again after 6 months or 1 year treatment, and fracture healing time was observed. The obtained data were statistically analyzed. Results:BMD of lumbar spine, neck of femur, trochiter and Ward’s triangular area were more significantly increased in experimental group than in control group (P<0.05). The comparisons of fracture healing time between two groups showed significant differences. Conclusion:After closed reduction

  15. Effect observation on treating malnutrition bone atrophy after calcaneal fracture surgery by Qianggu capsule plus salmon calcitonin%强骨胶囊配合鲑降钙素治疗跟骨骨折术后营养不良性骨萎缩疗效观察

    Institute of Scientific and Technical Information of China (English)

    郭鹏飞; 赵洪涛; 韩玉范

    2013-01-01

    Objective:To observe clinical effects of Qianggu capsule plus salmon calcitonin on treating malnutrition bone atrophy after calcaneal fracture surgery. Methods: 44 patients were given the Qianggu capsule plus salmon calcitonin. Results: Compared with before treatment, the total efficiency was over 72.8%. Conclusion:The Qianggu capsule plus salmon calcitonin was effective in treating malnutrition bone atrophy after calcaneal fracture surgery.%  目的:观察强骨胶囊配合鲑降钙素治疗跟骨骨折术后营养不良性骨萎缩的临床疗效。方法:对44例跟骨骨折术后出现营养不良性骨萎缩的患者,使用鲑鱼降钙素皮下注射,同时口服强骨胶囊进行治疗。结果:采用强骨胶囊配合鲑降钙素治疗44例跟骨骨折术后营养不良性骨萎缩患者,各种主要症状治疗前后对比,总有效率在72.8%以上。结论:用强骨胶囊配合鲑降钙素治疗跟骨骨折术后营养不良性骨萎缩是一种有效的治疗方法。

  16. Effects of Salmon Calcitonin on Bone Metabolism of Osteoporotic Femoral Neck Fracture and Bone Mineral Density%鲑鱼降钙素对骨质疏松性股骨颈骨折骨代谢及骨密度的影响

    Institute of Scientific and Technical Information of China (English)

    刘卓; 孙琪

    2014-01-01

    To investigate the effect of salmon calcitonin on bone metabolism of osteoporotic femoral neck fracture and bone mineral density.Methods:86 cases of femoral neck fracture patients were randomly divided into two groups:treatment group and control group,All patients were performed with surgical treatment,The treatment group used the salmon calcitonin combined calcium,Control group simply used calcium.Results:Blood calcium of treatment group increased,urine HOP declined obviously,femoral neck was a significant increase in the density,there was a significant difference compared with control group (P<0.05).Conclusion:Salmon calcitonin on bone metabolism in blood calcium,urine HOP and femoral neck bone mineral density has significant effect.%目的:探讨鲑鱼降钙素对骨质疏松性股骨颈骨折骨代谢及骨密度的影响。方法:选取86例股骨颈骨折患者,随机分为两组:治疗组和对照组,两组患者均采用手术治疗,治疗组采用鲑鱼降钙素联合钙剂治疗,对照组单纯使用钙剂治疗。结果:治疗组血钙值增加,尿HOP明显下降,股骨颈密度较治疗前显著增加,与对照组相比有显著差异(P<0.05)。结论:鲑鱼降钙素对骨代谢中血钙、尿HOP及股骨颈骨密度有显著影响。

  17. 鲑鱼降钙素联合钙尔奇D对老年髋部骨折患者腰椎骨密度的影响%Effect of Salmon Calcitonin combined Caltrate on lumbar vertebra BMD of elder patients with hip fracture

    Institute of Scientific and Technical Information of China (English)

    平少华; 梁春雨; 朱艳丽; 白月民; 屠世韵; 胡娜; 常婷婷

    2012-01-01

    目的 观察鲑鱼降钙素联合钙尔奇D对改善老年髋部骨折后卧床患者腰椎骨密度的临床疗效.方法 将30例患肢行胫骨结节骨牵引术的老年髋部骨折患者随机分为两组,治疗组15例,采用鲑鱼降钙素联合钙尔奇D进行治疗8周.对照组15例,未接受治疗.对比观察两组治疗前后腰椎骨密度(BMD)的变化情况.结果 对照组患者腰椎BMD较治疗前减低,差异有统计学意义(P 0.05).结论 鲑鱼降钙素联合钙尔奇D可以预防老年髋部骨折后卧床患者的腰椎骨质流失,预防废用性骨质疏松.%Objective To assess the effects of Salmon Calcitonin combined Caltrate on BMD of lumbar vertebra in elder patients with hip fracture. Methods 30 elder patients in bed with hip fracture were divided into two groups. Patients in treatment group were treated by Salmon Calcitonin combined Caltrate for 8 weeks while patients in control group weren't. BMD of lumbar vertebra was measured after 8 weeks. Results BMD of lumbar vertebra was found to reduce in the control group after treatment (P 0.05). Conclusion Salmon Calcitonin combined Caltrate is effective in preventing BMD of lumbar vertebra from reducing in elder patients with hip fracture.

  18. 骨化三醇联合鲑鱼降钙素治疗肾性骨病的临床疗效分析%Therapeutic Analysis of Combination of Calcitriol and Salmon Calcitonin on Renal Osteodystrophy

    Institute of Scientific and Technical Information of China (English)

    陈景; 唐东兴; 张琳; 章可铸

    2014-01-01

    Objective To analyse the clinical efficacy of the calcitriol and salmon calcitonin combination therapy on renal osteodystrophy. Method 30 patients suffered from renal osteodystrophy were treated with calcitriol ( control group, n=15) or calcitriol and salmon calcitonin (CSC group,n=15),respectively. The clinical efficacy,biochemical indicators and adverse reactions were compared. Results Bone pain,joint pain,skin itching and other symptoms after treatment have improved compared with those before treatment. The total clinical effective rate in CSC group was significantly higher than that in the control group (P<0. 05). After treatment,the serum phosphorus and PTH levels were decreased in varying degrees compared with that before treatment and serum calcium levels were elevated (P<0. 05). Indicators of treatment group improved more obviously compared with that in control group (P<0. 05). No adverse effects were found in the two groups during the medication. Conclusion Combination of calcitriol and salmon calcium in treatment of renal osteodys-trophy can effectively alleviate the clinical symptoms,such as bone pain,joint pain,and itchy skin,etc,which is worthy of being recommended.%目的分析骨化三醇和鲑鱼降钙素联合治疗肾性骨病的临床疗效。方法回顾分析2010年1月~2012年12月在本院治疗的肾性骨病患者30例,选择经骨化三醇联合鲑鱼降钙素治疗患者为治疗组,单纯运用骨化三醇治疗的患者为对照组,每组15例。比较两组临床疗效、生化指标改善情况及不良反应发生情况。结果两组患者治疗后骨痛、关节痛、皮肤瘙痒等临床症状均较治疗前有不同程度的改善,联合组患者临床总有效率明显高于对照组(P<0.05)。两组患者治疗后血清磷和PTH水平均较治疗前有不同程度的下降,而血清钙水平较治疗前有不同程度的升高(P<0.05)。两组患者服药期间未发现明显不良反应。结论骨化三醇联合鲑

  19. The mesurements of calcitonin gene-related peptide and substance P in patients with chronic cor pulmonale%慢性肺源性心脏病患者血浆CGRP和SP水平的测定

    Institute of Scientific and Technical Information of China (English)

    王珍珍; 谢新立; 阮翘

    2010-01-01

    目的 探讨血浆降钙素基因相关肽(calcitonin gene-related peptide,CGRP)和P物质(substance P, SP)在慢性肺源性心脏病(肺心病)发生发展中的病理生理作用.方法 采用放射免疫分析法测定30例肺心病组急性发作期和治疗后缓解期及20例正常对照组血浆CGRP和SP 浓度.肺心病组同时检测动脉氧分压(PaO2).结果 血浆CGRP水平肺心病组急性发作期(12±5)pg/ml和治疗后缓解期(19±7)pg/ml均低于正常对照组(24±5)pg/ml,差异有统计学意义(P0.05).PaO2急性发作期和治疗后缓解期分别为(6.3±2.0)kPa、(9.5±1.6)kPa,差异有统计学意义(P<0.01).结论 慢性缺氧与血浆CGRP、SP水平下降有关,尤其是CGRP,缺氧时两者的变化共同促进了肺动脉高压的形成,在慢性肺源性心脏病发生发展中起重要作用.%Objective To evaluate the pathophysiological role of calcitonin gene-related peptide(CGRP) and substance P(SP) in patients with chronic cor pulmonale. Methods The levels of plasma CGRP and SP were determined by radioimmunoassay in 30 patients with chronic cor pulmonale before and after treatment, and their mean pulmonary aterial pressure(PaO2) were detected. Control group consisted of 20 healthy subjects and the levels of plasma CGRP and cor pulmonale group, plasma CGRP levels before treatment(12±5 pg/ml)were lower than those after treatment(19±7)pg/ml(P<0.01). Both of them were lower than those in control group(24±5)pg/ml(P<0.01). Plasma SP levels before treatment(39±12)pg/ml were significantly lower than those after treatment(46±11)pg/ml (P<0.01), and control group(45±8)pg/ml(P<0.05), and there after treatment in chronic cor pulmonale group, PaO2 were (6.3±2.0)kPa and (9.5±1.6)kPa respectively, the former was significantly lower than the latter(P<0.01). Conclusions This study suggests that hypoxia has a statistical relationship with the decrease of plasma CGRP and SP levels in patients with chronic cor pulmonale, particularly with

  20. 鲑鱼降钙素联合金天格胶囊治疗老年性骨质疏松症的临床观察%Clinical observation of salmon calcitonin combined with Jintiange capsules in the treatment of senile osteoporosis

    Institute of Scientific and Technical Information of China (English)

    张学昌; 黄洪; 储辉; 张传飞

    2014-01-01

    目的:观察鲑鱼降钙素联合金天格胶囊治疗老年性骨质疏松症的临床疗效。方法将46例骨质疏松的患者随机分为治疗组和对照组,每组23例,治疗组采用鲑鱼降钙素联合金天格胶囊治疗骨质疏松,连续3个月为1疗程,对照组单独采用鲑鱼降钙素肌肉注射治疗骨质疏松,连续3个月为1疗程;评价治疗前后的疼痛缓解情况和腰椎骨密度( BMD)变化。结果对照治疗2个疗程后总有效率与对照组比较差异有统计学意义( P<0.05)。结论鲑鱼降钙素联合金天格胶囊治疗老年性骨质疏松症有效提高骨密度,缓解临床症状。%Objective To observe the clinical efficacy of salmon calcitonin combined with Jintiange capsules in the treatment of senile osteoporosis.Methods Forty-six patients with osteoporosis were randomly divided into the observation group and the control group, with 23 cases in each group.Patients in the control group were treated with the intramuscular injection of salmon calcitonin only.Patients in the observation group were treated with salmon calcitonin combined with Jintiange capsules.A consecutive 3-month treatment was considered as one treatment course.The pain relief and the changes of the lumbar bone mineral density ( BMD ) were evaluated.Results After two-course treatment, the total efficient rate in the observation group was significantly different compared with that in the control group ( P <0.05 ) .Conclusion Salmon calcitonin combined with Jintiange capsules can effectively improve BMD and relieve clinical symptoms in patients with senile osteoporosis.

  1. 74例老年骨质疏松患者应用鲑鱼降钙素联合阿仑膦酸钠治疗的疗效观察%The observation of the effect of salmon calcitonin combined with alendronate sodium on the treatment of senile osteoporosis

    Institute of Scientific and Technical Information of China (English)

    栾霞; 徐彤; 王学宏; 李荣娟

    2012-01-01

    Objective To evaluate the effect of salmon calcitonin combined with alendronate sodium on bone and joint pain, and to observe the changes of bone mineral density ( BMD) , and the serum concentrations of bone Gla protein (BGP) and calcitonin (CT) in senile osteoporosis patients. Methods Seventy-four senile osteoporosis patients in our hospital were treated with salmon calcitonin combined with alendronate sodium. All of them were given an intramuscular injection of 50 IU salmon calcitonin once every other day. After 15 continuous injections, they were given an oral medication of 1 capsule alendronate sodium once a week. The whole treatment lasted for 6 months. The degree of bone and joint pain before and after treatment was estimated with visual analogue scale (VAS). BMD of the lumbar vertebrae (L2-L4) , the femur neck, and Wards region was tested before and after the treatment. Serum concentrations of BGP and calcitonin were tested before and after the treatment. All the results were statistically analyzed. Results After 6-month treatment with salmon calcitonin combined with alendronate sodium in senile osteoporosis patients, the relief of pain in bone and joint was obvious , and the difference was significant ( P < 0. 01). BMD and the serum concentrations of BGP and calcitonin after the treatment were significantly different from those before the treatment (P < 0. 05 ). Conclusion The treatment with salmon calcitonin combined with alendronate sodium in senile osteoporosis patients can significantly improve BMD and serum concentration of calcitonin, and can reduce the serum concentration of bone Gla protein , relieve bone and joint pain in patients, ameliorate the symptoms, and increase BMD. It has an evident efficacy on senile osteoporosis .%目的 评估联合应用鲑鱼降钙素与阿仑膦酸钠治疗缓解老年性骨质疏松症患者骨关节疼痛及血清骨钙素(BGP)、降钙素(CT)及骨密度(BMD)水平的变化.方法 联合应用鲑鱼降钙素和

  2. 支气管哮喘患儿不同治疗方法内皮素和降钙素基因相关肽结果比较%Study of endothelin and calcitonin gene-related peptide levels in children with bronchial asthma by different therapies

    Institute of Scientific and Technical Information of China (English)

    吕汉文; 卢远达; 徐淑兰; 叶彩丽; 林灿华; 周翔

    2002-01-01

    Background: Bronchial asthma is an allergic pulmonary disease. The attack is mostly induced by the inhalation of or contact with allergens, such as pollens, dusts, insects (such as mite), germs, etc. During the attack, patients have severe dyspnea which is due to spasm of bronchial smooth muscles, swelling of the bronchial mucosa, and hypersecretion of the mucus, leading to bronchial obstruction. To observe the endothelin(ET) and calcitonin gene related peptide(CGRP) changes in treating children with bronchial asthma by dopamine( DP), dobutamine( DOB),and regitine.

  3. Cloning,Expression and Bioactivity of Tandem Salmon Calcitonin Gene%鲑鱼降钙素串联基因的克隆、表达及重组蛋白的生物学活性

    Institute of Scientific and Technical Information of China (English)

    黄迎春; 何璧梅; 张义正; 王欣荣

    2003-01-01

    目的:将鲑鱼降钙素(salmon calcitonin,sCT)基因以同向串联方式连接,构建串联多拷贝基因的表达质粒pHis-nCT(n≤3),并在原核中表达,研究表达产物的降钙活性.方法:采用半化学半酶促法合成sCT基因,利用基因的特点及特殊的酶切位点NdeI和SamI在表达载体pTrcHisC中进行sCT基因与载体基因的融合及sCT基因的串联,并在TOP10中表达串联多拷贝基因.表达产物形成包含体,对包含体变性、复性后,以Ni-Chelating Sepharose亲和纯化.用血清钙浓度测定法研究串联表达产物及裂解产物的降钙活性.结果:重组菌表达的串联融合蛋白经过变性、复性及亲合层析,纯度达到90%以上.活性试验表明,串联融合蛋白及其裂解产物可以抑制破骨细胞,降低血清钙浓度,且呈剂量效应关系.结论:原核表达质粒pTrcHisC可以有效表达串联的sCT基因,重组的串联蛋白及裂解产物均有降钙活性.

  4. Effect of Calcitonin on Bone Matrix Metalloproteinase 1,3 and 13 in Rabbits%降钙素对兔骨关节炎软骨基质金属蛋白酶1、3、13的影响

    Institute of Scientific and Technical Information of China (English)

    吕伟; 时剑辉; 崔巍; 单静

    2015-01-01

    目的:研究降钙素对兔骨关节炎软骨基质金属蛋白酶1、3、13的影响。方法60只日本大白兔被随机分为对照组(ACLT)、降钙素(CT)干预组,各30只。结果 CT组MMP-1、3、13的含量低于ACLT组(P<0.01)。结论降钙素对MMP-1、3、13的分泌有着一定的抑制作用,进而对骨关节炎进程有着相应的干预,使得骨关节炎的进展得以缓解和延缓。%Objective To study the effect of calcitonin on the matrix metaloproteinase 1,3 and 13 in rabbit osteoarthrit is.MethodsSixty Japanese white rabbits were randomly divided into control group(ACLT)and CTintervention group,each of which was divided into 30 groups.Results MMP-1,3 and 13 inCT group were much lower than that in ACLT group(P< 0.01). Conclusion Calcitonin can inhibit the process of MMP-1,3 and -13 in the process of bone arthritis,and delay the development of osteoarthritis.

  5. 应用鲑鱼降钙素及物理疗法联合治疗原发性骨质疏松症%Calcitonin combined with physical therapy for primary osteoporosis

    Institute of Scientific and Technical Information of China (English)

    赵法章; 韩雪松; 苏凤荣; 陶树清; 陶天遵

    2007-01-01

    目的 观察鲑鱼降钙素(Calcitonin, CT)和低频脉冲电磁场(low frequency transduction pulsed electromagnetic fields)治疗联合作用在治疗原发性骨质疏松症(primary osteoporosis)中的效果,比较联合作用与单纯应用药物所产生的效果的异同.方法 将存在骨质疏松性骨痛同时经DEXA骨密度仪(BMD machines)检测T值低于标准值2.0以下的老龄原发性骨质疏松症患者76人随机分为两组:①单纯应用鲑鱼降钙素组(36人);②联合应用药物及低频电磁场组(36人),两组同时每日给予钙而奇D600片1粒,CT按每日肌肉注射50 IU,10 d后改为隔日肌注50 IU连续应用2个月,低频电磁场治疗采用天津金希统公司生产的XT2000B型OP治疗仪,频率为20~40 Hz,每天治疗20 min,共治疗30 d,6个月后复查骨密度.结果 两组均取得较好的镇痛效果(分别为84%和97%),同时骨密度均有所增加. 结论联合治疗能够更进一步增加腰椎骨密度,在镇痛方面也能取得更好的效果.

  6. 唑来膦酸、降钙素对骨生化标志物BAP、N-MID、β-CTX的影响%Effect of zoledronic acid and calcitonin on bone metabolic biochemical markers, BAP, N-MID, and β-CTX

    Institute of Scientific and Technical Information of China (English)

    孔西建; 吴丹; 叶进; 廉杰

    2013-01-01

    目的 通过监测绝经后骨质疏松症患者使用唑来膦酸、降钙素治疗前后骨代谢生化标志物的变化来分析二者对骨代谢的影响.方法 回顾性分析绝经后骨质疏松症病例115例,55例使用唑来膦酸(5mg静滴一次),60例使用鲑鱼降钙素(50IU隔日一次肌注,治疗90日),检测每个病例治疗前和开始治疗后4周、8周、12周的BAP、N-MID、β-CTX,并进行统计学分析.结果 降钙素组治疗4周后BAP、β-CTX与治疗前相比降低(P<0.05),骨转换率降低;治疗8周、12周后β-CTX仍明显降低(P<0.05),但BAP与治疗前相比变化无统计学意义;唑来膦酸组治疗4周、8周后BAP、N-MID、β-CTX与治疗前相比均明显降低(P<0.05),骨转换率明显降低;治疗后12周后BAP、β-CTX仍明显降低(P<0.05);与降钙素组相比,唑来膦酸组治疗后4周、8周BAP、N-MID、β-CTX降低更明显(P<0.05),骨转换率降低更明显;治疗后12周BAP、β-CTX仍明显降低(P<0.05).两种药物均具有较好的安全性.结论 降钙素组、唑来膦酸组均可有效抑制骨吸收,降低骨转换率;与降钙素相比,唑来膦酸抑制骨吸收的作用更迅速、更稳定,病人低骨转换持续时间更久.%Objective To analyze the effect of zoledronic acid or calcitonin on bone metabolism by monitoring the changes of bone metabolic markers before and after the treatment of zoledronic acid or calcitonin in patients with postmenopausal osteoporosis. Methods The data of 115 patients with postmenopausal osteoporosis was analyzed retrospectively. Fifty-five patients were treated with zoledronic acid ( 5mg intravenous drip once ). Sixty patients were treated with salmon calcitonin ( 50U intramuscular injection every other day, lasting for 90 days ). BAP, N-MID , and β-CTX was tested before and 4-, 8-, and 12-week after the treatment. All the results were analyzed statistically. Result BAP and β-CTX in patients in calcitonin treatment group after 4-week treatment were

  7. 鲑鱼降钙素联合低频脉冲电磁场治疗绝经后妇女骨质疏松症的临床观察%Clinical observation of salmon calcitonin combine with low frequency PEMFs for the treatment of osteoporosis in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    梁莉萍; 王立

    2013-01-01

    目的:通过对鲑鱼降钙素联合低频脉冲电磁场( pulsed electromagnetic fields ,PEMFs)治疗绝经后骨质疏松症患者疗效的观察及分析,为绝经后骨质疏松症寻找到安全可靠,更具有良好疗效的治疗方案。方法选择90个病例,随机分为3组:A组为试验组:联合应用鲑鱼降钙素及低频电磁场组(30人);B组为对照组1:单纯应用低频电磁场组(30人);C组为对照组2:单纯应用鲑鱼降钙素组(30人),每组同时每日给予一定剂量的钙剂及维生素D;A、C组肌注鲑鱼降钙素(CT)50 U,1次/d,连续1 w,然后隔天1次,连续1 w,最后每周2次至疗程结束;A、B组均采用天津市同业科技发展有限公司生产的TY-PEMF-B型OP治疗仪实施低频电磁场治疗,频率8~16Hz,每次治疗40 min,共治疗30次;治疗前及治疗后第2、4、8周分别测定患者视觉模拟痛疼评分( VAS),并对3组患者进行治疗前及治疗后3、6个月腰椎及股骨颈BMD的测量。结果鲑降钙素联合骨质疏松治疗仪与单纯使用降钙素治疗或骨质疏松治疗仪治疗相比骨密度显著提高,试验组与对照组对比P<0.05。结论鲑降钙素联合骨质疏松治疗仪治疗绝经后妇女骨质疏松症疗是一种安全、疗效更好的方法。%Objective By observing and analyzing the efficacy of salmon calcitonin combine with low frequency PEMFs for the treatment of osteoporosis in postmenopausal women , to seek a safe, reliable, and more effective treatment plan for the treatment of osteoporosis in postmenopausal women .Methods Ninety patients were selected and randomly divided into 3 groups (n=30, each):study group (Group A), control group 1 (Group B), and control group 2 (Group C).Patients in Group A were treated with salmon calcitonin combined with PEMFs .Patients in Group B were treated with PEMFs only .And patients in Group C were treated with salmon calcitonin only

  8. 鲑鱼降钙素鼻喷剂治疗绝经后骨质疏松患者骨密度及骨转换指标的变化%Changes in bone mineral density and bone turnover in postmenopausal osteoporotic patients treated with salmon calcitonin nasal spray

    Institute of Scientific and Technical Information of China (English)

    宋利格; 孟祥君; 轩应利; 杨浩; 李红; 宣淼; 张秀珍

    2011-01-01

    Objective To study the changes of bone mineral density(BMD)and bone turnover in postmenopausal osteoporotic patients treated with salmon calcitonin nasal spray. Methods Sixty-seven postmenopausal osteoporotic patients were enrolled in our trial. All of them received calcium and vitamin D; 37patients were treated with salmon calcitonin nasal spray for 12 months and the other 30 patients received calcium and vitamin D only. Dual-energy X-ray absorptiometry(DEXA)and measurements of a series of bone turnover indices were performed before and after medication for 6 and 12 months. Results After treatment with salmon calcitonin nasal spray for6 months, BMD in lumbar spine 2-4 increased but no change occurred in femoral neck. However, after treatment for 12 months, BMD in both lumbar spine 2-4 and femoral neck increased. In the control group, BMD in lumbar spine 2-4 decreased after treatment for 6 and 12 months, but BMD in femoral neck decreased only after 12months. Comparing with the control group, after treatment with salmon calcitonin nasal spray, BMD in lumbar spine 2-4 and femoral neck were increased obviously. The level of TRACP-5b and NTX/Cr decreased after treatment with salmon calcitonin nasal spray for6 months and 12 months, while BALP increased only after treatment for 12 months. In the control group, BALP decreased after treatment for 12 months. The level of 25-(OH)vitamin D increased after treatment for 6 months and 12 months in both groups. Conclusions Long-term treatment with salmon calcitonin nasal spray prevents bone loss and may increase bone mass.%目的 观察鼻喷鲑鱼降钙素(calcitonin)治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者6个月和12个月后骨密度及骨转换指标的变化.方法 选择PMO患者共67例,给予鼻喷降钙素治疗37例;其余30例PMO患者单纯服用钙剂和维生素D作为对照组.各组分别于用药前和用药后6个月和12个月采用DEXA骨密度仪测定骨密度;定量

  9. Application of Salmon Calcitonin Calcium Combined with Vitamin D in the Prevention of Falls in Elderly Patients with Osteoporosis after Total Hip Arthroplasty%鲑鱼降钙素联合维生素D在预防老年骨质疏松患者全髋关节置换术后跌倒中的应用

    Institute of Scientific and Technical Information of China (English)

    王英东; 孙永新

    2015-01-01

    Objective: To explore the salmon calcitonin combined with vitamin D on the prevention of aging prevention function after total hip arthroplasty osteoporosis patients with accidental falls.Methods:The study included 49 patients,the patients were randomly divided into combined treatment group (salmon calcitonin and vitamin D) and control group (25 cases treated only with vitamin D preparation) in 24 cases,two groups of patients between the baseline levels of good consistency. All patients underwent total hip replacement surgery,postoperative medication and were followed up for 6 months,the number of monitoring patients fall and fracture rates.Results:In the treatment group,the incidence of falls was 24% and the control group the incidence rate was 25%,no cases of fracture in both two groups.Two groups of patients with postoperative follow-up of 6 months to fall and fracture incidence was no significant difference.Conclusion:The combined application of salmon calcitonin in elderly patients after total hip replacement in the treatment of osteoporosis,vitamin D did not influence the effect of fall prevention.%目的:探究鲑鱼降钙素联合维生素D对预防老龄全髋关节置换术后骨质疏松患者意外跌倒的预防作用.方法:研究纳入患者49例,将患者随机分为联合用药组(鲑鱼降钙素+维生素D)25例及单纯对照组(仅给予维生素D制剂)24例,两组患者间基线水平一致性良好.患者均行全髋关节置换术,术后用药并随访6个月,监测患者跌倒次数及相关骨折发生率.结果:联合治疗组跌倒发生率为24%,单纯对照组发生率为25.0%,两组均无再骨折病例.两组患者术后随访6个月时意外跌倒及再骨折发生率无显著差异.结论:联合应用鲑鱼降钙素作为老龄患者全髋关节置换术后抗骨质疏松治疗方案,未影响维生素D预防跌倒作用.

  10. Prevention of senile osteoporosis patients from thoracolumbar vertebral compression fractures with salmon calcitonin%鲑鱼降钙素预防老年性骨质疏松患者发生胸腰椎压缩性骨折的研究

    Institute of Scientific and Technical Information of China (English)

    郭杰坤; 陈沐吉; 何文英; 曾丽; 李远强

    2011-01-01

    Objective To research on the preventive function of salmon calcitonin in thoracolumbar fractures during treatment of senile osteoporosis. Methods The study accumulated 84 cases of senile osteoporosis who were randomly divided into group A and group B, wherein group A was intramuscularly injected with salmoncalcitonin and orally took calcium for three months, group B only orally took calcium for 3 months; the patients were followed up each month during later three years with the use of X-ray examination, and the case numbers of thoracolumbar vertebral compression fractures in group A and group B were obtained. Results Sixty-four cases were followed up, including 34 cases in group A with 6 cases of fracture, and 30 cases in group B with 12 cases of fracture; and the two groups had prominent differences by Pierxunka-square tes. ( P < 0. 05 ). Conclusions A valid preventive effects of salmon calcitonin on compression fracture of thoracic and lumbar vertebra in patients with osteoporosis were validated; Salmon calcitonin can releave bone pain of thoracic and lumbar vertebra effectively and safely,which is caused by Osteoporosis.%目的 研究鲑鱼降钙素在老年性骨质疏松治疗中对胸腰椎骨折的预防作用.方法 84例老年性骨质疏松患者,随机分成A,B两组,其中A组肌注鲑鱼降钙素和口服钙剂3个月,B组口服钙剂3个月;之后3年间每月随诊并行胸腰椎X线检查,统计A,B两组发生胸腰椎压缩性骨折的例数.结果 64人得到随诊,其中A组34例,发生骨折为6例;B组30例,发生骨折为12例;经皮尔逊卡方检验,两组间差异无统计学意义(P<0.05).结论 鲑鱼降钙素能有效预防老年性骨质疏松患者发生胸腰椎压缩性骨折,并能有效缓解骨质疏松引起的胸腰背部疼痛,安全性好.

  11. The Comparison of Immune Turbidimetric Method and Immunofluorescence Quantitative Analysis Method in the Measurement of Serum ;Calcitonin Original%免疫比浊法与免疫荧光定量分析法测量血清降钙素原比较

    Institute of Scientific and Technical Information of China (English)

    李秉忠

    2015-01-01

    Objective:To compare the results of the immune turbidimetric method and immunofluorescence quantitative analysis method in the measurement of serum calcitonin original.Method:202 cases of different concentrations of serum calcitonin were selected,they were all checked by zhejiang ransom biotechnology co.,LTD.Production of latex enhanced immune turbidimetry and guangzhou Wan Fu biological immunofluorescence quantitative analysis production company at the same time,the results and data statistics were analyzed.Result:the concentration values of the two methods in elevated group,the low risk group,negative group had no statistically significant(P>0.05);the concentration values of the two methods in highly group and moderately elevated group concentration had significant difference(P0.05).Conclusion:Immune turbidimetry and immunofluorescence quantitative analysis can be used for clinical serum calcitonin original detection,and immunofluorescence operation is more simple.%目的:比较免疫比浊法和免疫荧光定量分析法在测量血清降钙素原时的结果。方法:选取把在笔者所在医院进行降钙素检测的202例浓度不同的血清降钙素,分别用浙江兰森生物科技有限公司生产的乳胶增强免疫比浊法和广州万孚生物公司生产的免疫荧光定量分析法同时进行监测,并对结果和数据进行统计学的分析。结果:经比较,这两种方法在轻度升高组、低风险组、阴性组的浓度值方面比较,差异无统计学意义(P>0.05);在高度和中度升高组的浓度值方面比较,差异有统计学意义(P0.05)。结论:免疫比浊法和免疫荧光定量分析法均可用于临床血清降钙素原的检测,且免疫荧光法操作比较简便。

  12. 鲑鱼降钙素鼻喷剂对老年股骨转子间骨折术后康复的临床研究%Clinical study of salmon calcitonin nasal spray on senile femoral intertrochanteric fracture after

    Institute of Scientific and Technical Information of China (English)

    陈方经; 欧阳跃平; 苟三怀; 刘岩; 徐盛明; 叶添文; 史国栋

    2011-01-01

    目的 研究鲑鱼降钙素鼻喷剂对老年人股骨转子间骨折内固定术后的临床疗效.方法 采用完全随机对照的前瞻性临床研究方法,将入组的60例股骨转子间骨折老年患者分为两组,试验组行内固定手术并给予鲑鱼降钙素鼻喷剂及钙尔奇D治疗,对照组行内固定手术及钙尔奇D治疗.观察两组术后1、2,3、4周疼痛视觉模拟评分(VAS)、术后3个月骨折愈合及患髋关节功能情况.结果 鲑鱼降钙素鼻喷剂能明显减轻患者术后疼痛(P<0.001).术后3个月试验组骨折愈合率(89.3%)高于对照组(65.5%),P<0.05.术后3个月试验组患侧Harris髋关节功能评分优于对照组(P<0.05).结论 鲑鱼降钙素鼻喷剂具有一定的减轻老年股骨转子间骨折患者术后疼痛的作用,有助于促进骨折愈合及术后髋关节功能康复.%Objective To observe the efficacy of salmon calcitonin nasal spray on patients of senile femoral intertrochsnteric fracture after internal fixation surgery. Methods Using a fully randomized controlled research method, 60 cases of senile femoral intertrochanteric fracture were divided into two groups, 30 cases in experimental group were given salmon calcitonin nasal spray and Caltrate D and 30 cases in control group were given Caltrate D. The visual analogue scale(VAS) scores were evaluated in four weeks after surgery. The fracture healing and the function of hip were assessed after 3 weeks. Results Salmon calcitonin was effected for the patients reducing pain after internal fixation of femoral intertrochanteric fractures than the patients of the control group (P<0.001), the fracture healing rates in the experimental group and the control group were 89.3% and 65.5%respectively at 3 months, the difference has statistically significance(P<0.05). The experimental group is higher in Harris hip score than the control group (P<0.05). Conclusions Salmon calcitonin nasal spray can reduce postoperative pain in

  13. Salmon calcitonin nasal spray in combination with pulse electromagnetic field therapeutic apparatus in the treatment of osteoporotic lumbago curative effect observation%鲑鱼降钙素鼻喷剂结合脉冲电磁场治疗仪治疗骨质疏松性腰痛疗效观察

    Institute of Scientific and Technical Information of China (English)

    张宝; 韩守安; 孙永功; 胡铮

    2014-01-01

    Objective To evaluate the clinical efficacy of salmon calcitonin nasal spray combined with pulsed electromagnetic field therapy device for the treatment of osteoporosis, low back pain.Methods Our hospital in December 2012 - June 2014 osteoporotic patients treated with low back pain during the 78 cases and in accordance with randomly grouped into control group and observation group, 39 cases in each group. The control group with salmon calcitonin nasal spray treatment, observation group of salmon calcitonin nasal spray combined with pulsed electromagnetic field therapy instrument. Two groups of patients were observed before and after treatment pain scores and adverse reactions.Results Pain score before treatment observation group was(6.67±1.02) points to the control group(6.71±1.03) points, the difference was statistically significant(P> 0.05). After treatment, patients pain score was observed (1.47±0.36) points in the control group(3.69±0.53) points, both groups were significant decline, but the observation group than the control group(P<0.05). In addition, the observation group was 2.56% of adverse reactions(1/39) was significantly lower than the control group, 10.26%(4/39)(P<0.05). ConclusionOsteoporotic patients with low back pain salmon calcitonin nasal spray combined with pulsed electromagnetic fields therapeutic equipment, which can effectively relieve pain in patients with fewer side effects, worthy of promotion and application.%目的:探讨鲑鱼降钙素鼻喷剂结合脉冲电磁场治疗仪治疗骨质疏松性腰痛的临床疗效。方法选择2012年12月~2014年6月期间收治的骨质疏松性腰痛患者78例并按照随机数字表法分组为对照组和观察组,每组39例。对照组采用鲑鱼降钙素鼻喷剂治疗,观察组采用鲑鱼降钙素鼻喷剂结合脉冲电磁场治疗仪治疗。观察两组患者治疗前后疼痛评分情况及不良反应。结果治疗前观察组患者疼痛评分为(6.67±1.02

  14. 鲑鱼降钙素新型注射用温度敏感原位凝胶系统的构建及评价%Preparation and characterization of a novel injectable thermosensitive in situ gel containing salmon calcitonin

    Institute of Scientific and Technical Information of China (English)

    丁维明; 李艳芳; 李桂玲

    2014-01-01

    Objective To prepare the thermosensitive in situ gel of salmon calcitonin for injection and evaluate the characteristics and hypocalcemic effect. Methods Poloxamer F127 and poloxamer F68 were used to prepare the thermosensitive gel of samon calcitonin. The characteristics of the gel, such as gelation temperature, gelation time, rheological behavior and texture characteristics, were evaluated. Blood samples were drawn from orbit in rats, and coloration methods were used to monitor serum calcium ion concentration in order to study in vivo drug release and the hypocalcemic effect. Results The gelation temperature of the salmon calcitonin-loaded in situ gel was (35.3 ± 1.3)℃, and the gelation time was (108.3 ± 5.5) s. The in situ gel, a fluid solution at 25 ℃, became semisolid quickly at 37 ℃ due to the fact the viscosity and mechanical parameters such as gel strength for gel was enhanced at 37℃. The in situ gel loading sCT clearly decreased serum calcium level in rats over a longer period of time as compared with the conventional injection indicating sustained characteristic in vivo, and produced 138.6%hypocalcemic efficacy relative to common injection. Conclusion The thermosensitive in situ gel delivery system may be a promising candidate for injectable sustained delivery of salmon calcitonin.%目的构建鲑鱼降钙素新型注射用温度敏感原位凝胶系统并对其胶凝特性和降血钙效应进行评价。  方法以泊洛沙姆 F127为主要基质材料,复合使用泊洛沙姆 F68,制备鲑鱼降钙素注射用温度敏感原位凝胶给药系统,以胶凝温度、胶凝时间、流变学、质构特性为考察指标,对该凝胶系统性质进行评价;采用大鼠眼眶取血,钙显色法监测体内血清钙离子浓度,对该凝胶系统降血钙效应进行研究。  结果所制备的鲑鱼降钙素注射用温度敏感原位凝胶的胶凝温度为(35.3±1.3)℃,胶凝时间为(108.3±5.5)s,在25℃

  15. The clinical observation of percutaneous vertebroplasty combined with salmon calcitonin for the treatment of osteoporotic vertebral compression fracture%经皮椎体成形术联合鲑鱼降钙素治疗骨质疏松椎体压缩性骨折的临床观察

    Institute of Scientific and Technical Information of China (English)

    刘冬斌; 李辉; 程志安; 刘鹄; 刘汉辉; 任明亮

    2012-01-01

    Objective To observe percutaneous vertebroplasty (PVP) combined with salmon calcitonin for the treatment of patients with osteoporotic vertebral compression fracture ( OVCF) through comparative research. Methods The OVCF patients treated with PVP from Feb 2008 to Jan 2011 were randomly divided into two groups. The patients in treatment group were treated with intramuscular injection of salmon calcitonin after the operation for 3 weeks and nasal spray of salmon calcitonin after that at least for 3 months. The patients in control group were treated with PVP only. The clinical efficacies of the two groups were assessed with the visual analogue pain score ( VAS) and the capability of living score ( Barthel Index) before the operation, and 1 week, 1 month, 3 months, and 6 months after the operation, respectively. Results Pain of patients in both two groups was relieved significantly. However, the pain relieve at 1-, 3-, and 6-month after the operation and the improvement of life quality in the treatment group were more significant than those in the control group. This difference became more significant along with the follow up time. Conclusion PVP combined with salmon calcitonin can effectively relieve the pain of OVCF patients and improve their life quality. It is worthy of clinical promotion.%目的 通过对比研究,观察经皮椎体成形术联合密盖息治疗骨质疏松性椎体压缩骨折的疗效.方法 2008年2月至2011年1月,我们将脊柱压缩性骨折行PVP手术患者随机分成两组,治疗组在术后当日予以肌注鲑鱼降钙素,治疗3周后改用鼻喷剂,连续使用至少3个月;观察组单纯予以椎体成形术,分别在术前,术后1周,1月,3月以及6月采用VAS评分以及Barthel指数来评估两组治疗效果.结果 两组患者均在术后疼痛均有明显的缓解,但是相对于观察组,治疗组在术后1月,3月,以及6月疼痛缓解以及生活质量提高更为明显,随着随访时间的延长,这种

  16. The clinical research on the treatment of osteoporosis with calcitonin and low frequency pulse electromagnetic field%降钙素配合低频脉冲电磁场治疗骨质疏松症的临床研究

    Institute of Scientific and Technical Information of China (English)

    黄小娟

    2014-01-01

    Objective: To explore the clinical research on the treatment of osteoporosis with calcitonin and Low frequency pulse electromagnetic field. Methods:Selected 84 cases of primary osteoporosis were randomly divided into control group and treatment group, 42 cases in each group, two groups were given calcium, vitamin D and other drugs conventional treatment, on the basis of the control group, intramuscular injections salmon calcitonin in the treatment group and intramuscular injection of salmon calcitonin with PEMF therapy, before treatment and after 3 and 6 months, respectively. Results: Two groups of patients after treatment, the pain was significantly reduced compared with before treatment, the longer the treatment, the more obvious decline;Treatment of three months, six months later, the treatment group compared with the control group bone mineral density were significant differences(t=3.129, t=6.457;P<0.05);The two groups no serious adverse reactions. Conclusion:Osteoporosis patients in the conventional therapy treatment based on intramuscular injection of salmon calcitonin and with PEMF treatment can significantly reduce the patient's pain, increase bone density, efficacy, adverse reactions, with some clinical reference significance.%目的:探讨降钙素配合低频脉冲电磁场治疗骨质疏松症的临床疗效。方法:选取84例原发性骨质疏松患者,随机分为对照组和治疗组,每组42例。两组均给予碳酸钙、维生素D等常规药物治疗。在此基础上对照组肌内注射鲑鱼降钙素,治疗组肌内注射鲑鱼降钙素并配合低频脉冲电磁场治疗。并分别评估治疗前及治疗后3个月、6个月患者的疼痛疗效及检测骨密度。结果:两组患者治疗后疼痛较治疗前均明显减轻,治疗时间越长,疼痛减轻越明显;治疗3个月、6个月后,治疗组骨密度较对照组均有显著提高,其差异有统计学意义(t=3.129,t=6.457;P<0.05)

  17. Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis - the effect of sex, Kellgren-Lawrence (KL score, Body Mass Index (BMI, oral salmon calcitonin (sCT treatment and diurnal variation

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    Henriksen K

    2010-06-01

    Full Text Available Abstract Background Osteoarthritis (OA involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL score, Body Mass Index (BMI, oral salmon calcitonin (sCT treatment and diurnal variation. Methods This study was a 2-week, double-blind, double-dummy, randomized study including 37 postmenopausal women and 36 men, aged 57-75 years, with painful knee OA, and a KL-score of I - III. Subjects were allocated to one of three treatment arms: 0.6 mg or 0.8 mg oral sCT, or placebo given twice-daily for 14 days. Correlations between gender, KL score, or BMI and the bone resorption marker, serum C-terminal telopeptide of collagen type I (CTX-I, or the cartilage degradation marker, urine C-terminal telopeptide of collagen type II (CTX-II were investigated. Results At baseline, biomarkers indicated women with OA experienced higher bone and cartilage degradation than men. CTX-I levels were significantly higher, and CTX-II levels only marginally higher, in women than in men (p = 0.04 and p = 0.06, respectively. Increasing KL score was not correlated with bone resorption, but was significantly associated with the cartilage degradation CTX-II marker in both men and women (p = 0.007. BMI was significantly and negatively correlated to the bone resorption marker CTX-I, r = -0.40 (p = 0.002, but showed only a borderline positive correlation to CTX-II, r = 0.25 (p = 0.12. Before morning treatments on days 1 and 14, no correlation was seen between CTX-I and CTX-II in either the sCT or placebo group. However, oral sCT and food intake induced a clear correlation between these bone and cartilage degradation markers. Four hours after the first sCT dose on treatment days 1 and 14, a significant correlation (r = 0.71, p p = 0.02, but not on day 14. Conclusion Bone resorption was higher in

  18. Cloning and expression analysis of calcitonin gene related peptide (CGRP) in Gekko japonicus%多疣壁虎降钙素基因相关肽基因的克隆及表达分析

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    任丽洁; 王锐利; 王莹洁; 王勇军

    2012-01-01

    Objective To clone the full length of calcitonin gene related peptide (CGRP) in Gekko japonicus, and investigate the expression changes of CGRP in the spinal cord regeneration after tail amputation. Methods Full length of CGRP cDNA was obtained from Gekko by rapid amplification of cDNA ends ( RACE). Then the expression and distribution of CGRP in the proximal spinal cord were compared at different time points after tail amputation (P <0.05) by in situ hybridization (ISH) and RT-PCR. Results CGRP cDNA spans 1 002 bp. RT-PCR results showed that CGRP mRNA was remarkably up-regulated in the spinal cord proximal to the amputation at Id after tail amputation(P <0.05). In situ hybridization showed that CGRP mRNA was expressed mainly in the gray matter of spinal cord and scarcely in white matter. After tail amputation, the expression of CGRP was significantly increased in the proximal spinal cord of injury, at 1 d (P < 0.05). Conclusion Full length of CGRP cDNA was obtained. CGRP was remarkably up-regulated in the spinal cord proximal to the amputation at Id after tail amputation. CGRP synthesized and released from neural system may participate in regulating immunoreaction or wound healing.%目的 克隆多疣壁虎降钙素基因相关肽(CGRP)基因的全长序列;研究CGRP在壁虎断尾损伤后脊髓再生过程中的表达变化.方法 应用cDNA末端快速扩增(RACE)技术获得壁虎CGRP的cDNA全长序列;制备壁虎断尾损伤模型,应用RT-PCR和原位杂交方法检测壁虎断尾后该基因在中枢神经系统的表达变化.结果 RACE方法获得CGRPcDNA全长序列1 002bp;RT-PCR检测结果表明,壁虎断尾损伤1d后断端近侧脊髓中mRNA表达呈明显上升趋势且转录水平最高(P<0.05);脊髓原位杂交结果显示,CGRP mRNA阳性信号主要分布于脊髓灰质中,白质中少量表达;断尾损伤后1d阳性信号明显增强(P<0.05).结论 该试验克隆得到了壁虎CGRP cDNA的全长

  19. Influence of Buyang Huanwu Decoction on Endothelin and Calcitonin Gene-related Peptide in Patients with Migraine%补阳还五汤对偏头痛患者血浆CGRP和ET的影响

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    张洪涛; 张淑玲

    2013-01-01

    目的:观察补阳还五汤对偏头痛患者血浆降钙素基因相关肽(CGRP)和内皮素(ET)的影响.方法:72例偏头痛患者随机分为两组,西药组36例,口服尼莫地平20~40 mg,每日3次;急性发作期加服麦角胺咖啡因片1~2片/次.中药组36例,给予补阳还五汤,每日1剂,水煎分早晚服.两组均连续治疗3个月.治疗前、后监测偏头痛发作频率、持续时间、严重程度、药物的不良反应、CGRP和ET的水平,并与36例正常人对照.结果:中药组的总有效率显著高于西药组(P<0.05);两组偏头痛患者均较正常人ET明显增高(均P<0.01),CGRP明显降低(均P<0.01);西药组和中药组均可降低ET水平、偏头痛积分,提高CGRP水平(均P<0.01),但中药组比西药组作用更明显(均P<0.01).服用补阳还五汤未发生明显的不良的反应.结论:补阳还五汤能通过调节血管活性物质CGRP,ET水平,改善血管的异常舒缩状况,从而达到缓解偏头痛的作用.%Objective: To observe the influence of Buyang Huanwu decoction on endothelin (ET) and calcitonin gene-related peptide (CGRP) in patients with migraine. Method: Seventy two patients with migraine were divided into 2 groups randomly, 36 patients in western medicine group were treated by Nimodipine tablets 20-40 mg once, 3 times a day, To add ergotamine caffeine 1-2 tablets once in acute seizure phase. 36 patients in Chinese medicine group were treated by Buyang Huanwu decoction, take a decoction a day, divided into morning and evening. Patients had received continuous treatment for three months. Migraine frequency, duration, severity, adverse drug reactions and the concentration of plasma CGRP and ET were monitored before and after treatment. And comparative study with 36 cases of normal. Result: The total efficiency of traditional Chinese medicine group was significantly higher than that of the western medicine group (P < 0. 05 ) ; ET in patients with migraine was significantly

  20. Effect of combined treatment with calcitonin on bone densitometry of patients with treated hypothyroidism Influência da terapêutica associada com calcitonina sobre a densitometria óssea de pacientes com hipotiroidismo tratado

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    F. J. da C. Stamato

    2000-06-01

    Full Text Available INTRODUCTION: Thyroid hormones (TH may affect bone metabolism and turnover, inducing a loss of bone mass among hyperthyroid and in hypothyroid patients under hormone replacement treatment. Thyroid dysfunction leads to changes in the dynamics of parathyroid hormone (PTH and calcitonin (CT secretion. OBJECTIVE: The objective of the study was to determine the usefulness of CT as adjuvant therapy in the prevention of bone loss during the treatment of hypothyroidism. MATERIAL AND METHODS: We studied 16 female patients with recently diagnosed primary hypothyroidism, divided into two groups: group G1 (n=8 submitted to treatment with thyroxine (L-T4, and Group 2 (n=8 that, in addition to being treated with L-T4, received a nasal CT spray. All patients were submitted to determination of TSH, free T4, bone mineral densitometry (BMD and total bone calcium (TBC at the time of diagnosis, after 6 to 9 months of treatment, and after 12 months of treatment. RESULTS: No statistical significant differences were detected in either group between the total BMD values obtained for the femur and lumbar spine before and after treatment. However, group G1 presented a statistical significant TBC loss after 12 months of treatment compared to initial values. In contrast, no TBC loss was observed in the group treated with LT-4 in combination with CT, a fact that may suggest that CT was responsible for the lower bone reabsorption during treatment of hypothyroidism.INTRODUÇÃO: Os hormônios tiroidianos (HT podem influenciar o metabolismo e o "turnover" ósseo, induzindo perda de massa óssea em hipertiróideos e em hipótiroideos na vigência de reposição hormonal. As disfunções tiroidianas levam a alterações na dinâmica de secreção de paratormônio (PTH e de calcitonina (CT. OBJETIVO: Esclarecer a utilidade da CT como terapêutica coadjuvante na prevenção de perda óssea durante o tratamento do hipotiroidismo. MATERIAL E MÉTODOS: Dezeseis pacientes do sexo

  1. Levels of vasoactive intestinal peptide,cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction

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    Chun-Hua Hang; Ji-Xin Shi; Jie-Shou Li; Wei Wu; Wei-Qin Li; Hong-Xia Yin

    2004-01-01

    AIM: To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction.METHODS: Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VTP in jejunum. RESULTS: Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8±29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7±34.1 ng/L, 148.7±22.8 ng/L, 132.8±21.6 ng/L,respectively), but significantly increased at 72 h (405.0±29.8 ng/L) and markedly declined on d 7 (130.7±19.3 ng/L).However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBT (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6±1.4 ng/g; CGRP, 70.6±17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4±5.0 ng/g; CGRP, 103.8±22.1 ng/g), anddeclined gradually at 12 h and 24 h (VIP, 16.5±1.8 ng/g, 5.5±1.4 ng/g; CGRP, 34.9±9.7 ng/g, 18.5±7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7±9.5 ng/g; CGRP, 142.1±24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8±1

  2. Avaliação histométrica da ação local da calcitonina de salmão no processo de reparo ósseo: estudo em ratos Histometrical evaluation of the local effects of salmon calcitonin on the bone healing process: a study in rats

    Directory of Open Access Journals (Sweden)

    Emerson CANAVERO

    2000-06-01

    Full Text Available Neste estudo avaliou-se histometricamente a ação local da calcitonina de salmão em defeitos ósseos provocados cirurgicamente em fêmur de ratos. As avaliações foram feitas aos 7, 14 e 21 dias após o ato cirúrgico. Não se observou diferenças estatísticas aos 7 dias, entretanto no período de 14 dias houve diferenças com maior formação óssea no grupo tratado. No período de 21 dias, em ambos os grupos, não foi possível diferenciar o tecido ósseo neoformado e o adjacente. Os resultados demonstraram, que o efeito da calcitonina foi observado somente no início do processo de reparo dos defeitos ósseos criados cirurgicamente.The purpose of the present study was to histometrically evaluate the effects of salmon calcitonin on the bone healing of surgically created bone defects in rats. The animals were sacrificed 7, 14 and 21 days after the surgical procedure. After the 7- and 21-day periods, differences between the experimental and control groups were not observed (P > 0.01. After the 14-day period, a larger amount of new bone was observed in the experimental group (P < 0.01. Thus, within the limits of the present study, it can be concluded that although salmon calcitonin positively participated in the initial phase of bone healing, it did not result in a larger amount of new bone at the end of the experimental period.

  3. 降钙素及二膦酸盐治疗血液透析患者肾性骨病的长期疗效%Long-term efficacy of calcitonin and bisphosphonates on renal osteopathy in maintenance hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    石书梅; 赵学智; 陆烈; 卜磊; 陈意志

    2009-01-01

    Objective To observe the efficacy of ealcitonin and bisphosphonates on renal osteopathy of maintenance hemodialysis (MHD)patients. Methods Forty-three MHD patients were raindomly divided into two groups: A group and B group. All the patients were routinely received oral calcium carbonate 1.0 g tid and calcitriol 0.25 μg qd. Calcitonin (20U) hypodermic injection was given three times a week additionally during hemodialysis in A group. Patients in B group received bisphosphonates 70 mg once a week based on the therapy of A group. Serum levels of intact parathyroid hormone (iPTH), calcium, phosphorus, alkaline phosphatase (AKP), bone mass density (BMD) of lumbar spine and femoral neck, and the degree of bone ache (visual analogue scale, VAS) were assessed before the therapy and 3, 6 and 12 months after treatment. The adverse reactions were recorded during treatment. Results The levels of AKP and iPTH in both two groups decreased significantly after treatment. The above values of pre-treatment and 12 months after treatment were as follows: AKP(U/L)of A group 244.05±41.99 and 148.35±27.71,of B group 245.60±40.86 and 143.40±28.03;PTH(ng/L) of A group 697.5±119.7 and 267.4±45.9,of B group 708.2±120.3 and 277.6±41.9 (all P0.05). BMD was not improved at 3, 6 mouths and became better at 12 mouths after treatment. As compared to pre-treatment, BMD of lumbar spine(g/cm2) in A group was 1.062±0.223 vs 1.202±0.251 ,in B group 1.033±0.152 vs 1.189±0.225; BMD of femoral neck (g/cm2)in A group was 0.993±0.108 vs 1.067±0.095,in B group 0.947±0.083 vs 1.018 ±0.217 (all P<0.05). The scores of VAS also decreased significantly at 3, 6, 12 months after treatment(P<0.05). No severe adverse reaction was found during the treatment. Conclusions Utilization of calcitonin and combination with bisphosphonates during bemodialysis can effectively preserve the BMD and prevent bone loss in MHD patients and is well tolerated. No significant difference of therapeutic effect is

  4. 鲑鱼降钙素与骨水泥成形术治疗骨质疏松性椎体压缩骨折的临床比较%Treatment of osteoporotic vertebral compression fractures: clinical application of bone cementoplasty and Salmon calcitonin

    Institute of Scientific and Technical Information of China (English)

    李永刚; 唐海

    2012-01-01

    目的 探讨鲑鱼降钙素及骨水泥成形术治疗骨质疏松性椎体压缩骨折(Osteoporotic vertebral compression fractures OVCFs)的临床疗效.方法 回顾性分析66例OVCFs患者,应用骨水泥成形术治疗46例,其中椎体成形术(percutaneous vertebroplasty PVP)治疗25例,后凸成形术(percutaneous kyphoplasty PKP)治疗21例;鲑鱼降钙素等药物治疗20例.治疗后随访12~20个月,平均14个月,记录对比疼痛视觉模拟评分(Visual analogue scales VAS),用SF-12(Short Form-12)健康调查评分表评价其生活质量变化,记录骨水泥成形术组椎体高度变化和Cobb角改善情况,降钙素组骨密度变化情况.结果 所有患者腰背疼痛均有不同程度减轻,手术无明显并发症.VAS评分:各组治疗前后比较差异有统计学意义(P<0.05).术后1周骨水泥成形术组患者VAS评分优于降钙素治疗组(P<0.05);术后两周各组问VAS评分差异无统计学意义(P> 0.05); SF-12健康调查评分:各组治疗前后比较差异明显(P<0.05),组间差异不明显.伤椎压缩恢复程度:骨水泥治疗组伤椎Cobb角及椎体高度均有所改善,总体看PKP优于PVP (P< 0.01).骨密度变化:降钙素组骨密度治疗后有提高(P<0.05).结论 骨水泥成形术治疗OVCFs能够迅速缓解疼痛,改善椎体高度和Cobb角,增加脊柱稳定性;鲑鱼降钙素等药物治疗早期也可缓解疼痛,但止疼效果较骨水泥成形术滞后两周,药物及手术治疗均能明显提高患者生活质量.%OBJECTIVE To study the effect of therapies including bone cementoplasty and Salmon calcitonin in treating OVCFs. METHODS There WERE 66 cases of OVCFs.Fourty-six cases were treated with bone cementoplasty therapy, of which PVP was done in 25cases and PKP was done in 21 cases. Twenty cases was done with Salmon calcitonin. A follow up for 12-20 months (average 14 months) was carried out to compare VAS and SF-12 health survey, recorded the changes of vertebral height

  5. 降钙素基因相关肽对实验性心肌肥厚的影响%The Impact of Calcitonin Gene Related Peptide on Experiment Cardiac Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    张欣; 刘玉龙; 张海峰; 李春跃; 王美玲

    2011-01-01

    使用降钙素基因相关肽(CGRP)干预压力超负荷心肌肥厚大鼠,探讨CGRP与心肌组织中一氧化氮、内皮素含量变化的关系以及CGRP对心肌肥厚的影响,期望进一步揭示心肌肥厚的可能机制.采用腹主动脉缩窄的方法复制压力超负荷心肌肥厚大鼠模型.选取雄性Wistar大鼠40只,随机分为4组:对照组,缩窄组,CGRP组,卡托普利组(每组N=10).术后一周开始CGRP组给予CGRP8 μg/(kg·d-1),卡托普利组给予卡托普利30 mg/( kg·d-1).给药4周后处死动物,检测各项指标,光镜下观察心室肌组织结构变化,分别用放射免疫方法和硝酸还原法测定心室肌ET、NO的水平.与对照组相比的结果是缩窄组大鼠SBP、LVW/BW及心肌中ET水平明显升高(P<0.05),NO明显降低(P<0.05);干预组与缩窄组相比,SBP、LVW/BW及心肌中ET水平明显降低(P<0.05),心肌中NO水平升高(P<0.05),ET水平与左心系数呈正相关.光镜下观察结果:缩窄组与对照组比较,可见心肌纤维横径明显增粗,细胞核肥大,深染,异型,心肌纤维间隙增宽,间质纤维结缔组织增生明显.CGRP组和卡托普利组心肌纤维横径及细胞核较缩窄组缩小,间质增生程度较缩窄组明显减轻形态已经与对照组相近.说明:(1)心肌中NO水平下降、ET水平上调可能参与了压力超负荷性心肌肥厚的发生发展.(2) CGRP具有一定的逆转高血压心肌肥厚的作用,此作用与临床常用抗高血压药物卡托普利相近.%To investigate the relationship between calcitonin gene -related peptide (CGRP) and nitric oxide and endothelin ( ET) in myocardial tissue, and the impact of CGRP on cardiac hypertrophy of rats. Then the possible mechanism of cardiac hypertrophy is revealed. Hypertrophic myocardium was reproduced in rats by constricting abdominal aorta. 40 male Wistar rats were randomly divided into four groups; control group(N = 10) , coarctation group(Iv = 10) , CGRP group(N = 10

  6. ANALGESIC OUTCOME OF SALMON CALCITONIN AFTER TOTAL KNEE ARTHROPLASTY FOR THE ELDERLY PATIENTS WITH OSTEOPOROSIS%鲑鱼降钙素对老年骨质疏松症患者全膝置换术围手术期疼痛的影响

    Institute of Scientific and Technical Information of China (English)

    方忠; 夏天; 李光辉; 肖骏; 熊伟; 李锋; 夏仁云

    2011-01-01

    Objective: To observe the analgesic effect of salmon calcitonin after total knee arthroplasty (TKA) for the elderly patients with osteoporosis. Methods: Seventy-five patients undergoing unilateral TKA surgery were randomly divided into three groups (C, S and M). The patients in group C took salmon calcitonin 50 IU b.I.d. For 2 weeks, group S took celebrox 200 mg b.I.d for 7 days, and group M took both of them. All patients were assessed analgesic effect for 5 days. VAS pain scores were assessed during rest, initiative exercise and continuous passive movement (CPM), complications were recorded. Results: The VAS pain scores during rest, initiative exercise and CPM on the postoperative time of 24 h, 48 h, and 72 h in group M were significantly lower than those in group S and group C (P < 0.01). However, there were no significant difference observed between the 3 groups on the post-operative time of 96 h and 120 h. The TKA patients of the M group needed significantly less time for the range of movement (ROM) to arrive 90 degrees than the patients of S group (P < 0.01); The mean knee ROM of the patients in the M group was obviously larger than that of the S group (P < 0.01). There were no significant differences in number of complications between the 3 groups. Conclusion: After TKA surgery, salmon calcitonin in combination with celebrox can provide better pain relief than to use single calcitonin or celebrox.%目的:观察鲑鱼降钙素对老年骨质疏松症患者全膝关节置换术TKA围手术期疼痛的影响.方法:选择行单侧全膝关节置换术的老年合并骨质疏松症患者75例,随机分为鲑鱼降钙素组(C组n=25)、塞来昔布组(S组n=25)和鲑鱼降钙素+塞来昔布联合组(M组n=25).C组患者给予鲑鱼降钙素Calcitonin(50IU/次,2次/天),连续2周;S组患者术后口服西乐葆(200mg,2次/天),维持7天;M组则采取上述两组的联合用药.术后记录静息( RVAS)、主动(IVAS)和持续被动( PVAS)功能训练时

  7. Effect observation of calcitonin acetate,form salmon in the treatment of diabetic peripheral neuropathy combined with osteoporosis%鲑鱼降钙素治疗糖尿病周围神经病变伴骨质疏松的效果观察

    Institute of Scientific and Technical Information of China (English)

    刘婉贞

    2015-01-01

    目的:探讨鲑鱼降钙素治疗糖尿病周围神经病变(DPN)合并骨质疏松的效果。方法入选本院2011年4月~2013年4月收治的92例2型DPN合并骨质疏松患者,随机分为两组,各46例,对照组采用钙尔奇治疗,观察组在此基础上采用鲑鱼降钙素治疗,比较两组的疗效及治疗前后骨密度值。结果观察组总有效率93.5%(43/46)显著高于对照组的71.7%(33/46)(P<0.01)。观察组治疗后的BMD为(258.7±25.6)mg/cm2、BGP为(5.3±1.0)ng/ml,显著高于对照组的(235.5±25.3) mg/cm2和(4.5±0.9) ng/ml(P<0.01),PTH为(48.1±16.7) pg/ml,低于对照组的(54.2±17.4)pg/ml(P<0.05)。结论鲑鱼降钙素能显著提高2型DPN合并骨质疏松的疗效,并有效改善骨密度指标。%Objective To study the effects of calcitonin acetate,form salmon in the treatment of diabetic peripheral neu-ropathy (DPN)combined with osteoporosis. Methods 92 patients with type 2 DPN combined with osteoporosis treated from April 2011 to April 2013 in our hospital were selected and randomly divided into two groups,46 cases in each group.The caltrate was used in control group,caltrate combined with calcitonin acetate,form salmon were applied in ob-servation group.The effects and BMD before and after treatment in two groups were compared. Results Total efficacy rate of observation group was 93.5%(43/46),significantly higher than that of control group [71.7%,(33/46)](P<0.01).After treatment,BMD of observation group was (258.7±25.6) mg/cm2,BGP of observation group was (5.3±1.0) ng/ml,signifi-cantly higher than that of control group[(235.5±25.3) mg/cm2 and (4.5±0.9) ng/ml] respectively(P<0.01).After treatment, PTH of observation group was (48.1±16.7) pg/ml,lower than that of control group[(54.2±17.4) pg/ml](P<0.05). Conclu-sion Calcitonin acetate,form salmon can significantly improve the curative effects for type 2 DPN combined with osteo-porosis as well as

  8. The efficacy of Xianlinggubao capsule combined with alendronate sodium tablets and salmon calcitonin in the treatment for the patients with osteoporosis%仙灵骨葆胶囊联合阿仑膦酸钠片、鲑降钙素对骨质疏松症患者的治疗作用

    Institute of Scientific and Technical Information of China (English)

    曾文丛; 何伟

    2015-01-01

    Objective: To discuss the efficacy of Xianlinggubao capsule combined with alendronate sodium tablets and salmon calcitonin in the treatment of the patients with osteoporosis. Methods: Seventy-nine outpatients and inpatients with osteoporosis in our hospital from May, 2013 to May, 2014 were selected and divided into a control group (n=39, received alendronate sodium tablets and salmon calcitonin treatment) and an observation group (n=40, received Xianlinggubao capsule on the basis of the control group) by digital randomized method. The clinical efficacy was compared between two groups. Results:The efficiency and treatment effectiveness of the observation group were significantly higher than those of the control group (P0.05). The BMD of the observation group was significantly higher 3 ~ 12 months after treatment than before, and that of the control group. The S-P, S-Ca and BGP levels of all patients were significantly higher while the serum ALP was significantly lower after treatment than before (P0.05). Conclusion: Xianlinggubao capsule combined with alendronate sodium tablets and salmon calcitonin shows an obvious therapeutic effect in the treatment of the patients with osteoporosis and can improve bone metabolism index.%目的:探讨仙灵骨葆胶囊联合阿仑膦酸钠片、鲑降钙素对骨质疏松症患者的治疗作用。方法:选取2013年5月-2014年5月期间我院门诊和住院部就诊的骨质疏松症患者79例,采用随机数字表法将患者分为对照组(n=39,阿仑膦酸钠片联合鲑降钙素药物治疗)和观察组(n=40,在对照组基础上采用仙灵骨葆胶囊治疗),比较两组临床疗效。结果:观察组显效率和治疗有效率均明显高于对照组(P <0.05)。治疗前,两组患者骨密度值(BMD)、血磷(S-P)、血钙(S-Ca)、血清碱性磷酸酶(ALP)和血骨钙素(BGP)水平比较差异无统计学意义(P >0.05)。治疗3~12个月后,观察组 BMD 值

  9. Study for the effect on pain and bone mineral density by salmon calcitonin nasal spray for osteoporosis%鲑鱼降钙素鼻喷剂对骨质疏松性疼痛和骨密度的影响研究

    Institute of Scientific and Technical Information of China (English)

    任平

    2011-01-01

    Objective To study the effect on pain and bone mineral density by salmon calcitonin nasal spray for osteoporosis.Method 106 patients with osteoporotic pain were randomly divided into treatment and control group, 53 patients in each group, and two groups of patients were given malic acid calcium citrate, exercise, eating the same mission.Treatment group were treated with nasal spray salmon calcitonin, nasal spray two times every day, while control group were not.The degrees of bone mineral density and pain in two groups were measured and compared before and after the treatment.Result The average bone mineral density for both groups was increased after treatment(P<0.01), and the Pain for both groups was increased after treatment(P<0.01 ).The effect in treatment group was better than that of control group.There is significant difference between the two groups(P<0.01).Conclusion Patients' osteoporosis pain can been effectively relieved, and bone density improve by application of salmon calcitonin nasal.It has advantages of medication convenience, safety, high patient compliance for improving the patients' quality of life.%目的 探讨鲑鱼降钙素鼻喷剂对骨质疏松性疼痛和骨密度的影响.方法 将106例骨质疏松性疼痛患者随机分成观察组和对照组各53例,两组患者均给予枸橼酸苹果酸钙进行补钙治疗,运动、饮食宣教一致.观察组加用鲑鱼降钙素鼻喷剂喷鼻,每天喷2次,治疗2个月后对两组患者治疗前后骨密度测定及疼痛程度进行比较.结果 两组患者治疗后的骨密度值均明显增加(P<0.01).疼痛程度明显改善(P<0.01),且观察组疗效明显优于对照组(P<0.01)·差异有极显著意义.结论 应用鲑鱼降钙素鼻喷剂治疗骨质疏松性疼痛,能有效缓解患者疼痛和提高骨密度,且用药方便、安全,患者依从性高,能提高患者生活质量.

  10. Analysis the effect of salmon calcitonin combined with azole phosphonic acid in the treatment of osteoporosis in elderly men%鲑鱼降钙素联合唑来膦酸治疗老年男性骨质疏松症的效果分析

    Institute of Scientific and Technical Information of China (English)

    冯缨缨; 钟远; 金俊

    2015-01-01

    ObjectiveTo explore the effect of salmon calcitonin combined with azole phosphonic acid in the treatment of osteoporosis in elderly men.Method173 cases of elderly male patients with osteoporosis were randomly divided into control group and experimental group, the two groups of patients were given oral calcium supplements, on the basis of the control group patients were given salmon calcitonin nasal spray, experimental group patients were given azole phosphonic acid injection, a course of 1 year. Compared the two groups of patients with clinical efifcacy, bone mineral density (BMD) before and after treatment, serum bone alkaline phosphatase (BAP), serum the C-terminal peptide (CTX) type I collagen levels and adverse reactions.ResultThere was no signiifcant difference of BMD between the two groups before treatment (P>0.05); BMD in both groups after treatment were higher than before treatment (P0.05).ConclusionSalmon calcitonin combined with azole phosphonic acid can effectively improve the elderly male patients with osteoporosis bone mineral density, curative effect is distinct, worth of clinical promotion.%目的:探究鲑鱼降钙素联合唑来膦酸治疗老年男性骨质疏松症的临床效果。方法将本院收治的173例老年男性骨质疏松症患者随机分为对照组及试验组,两组患者均给予口服钙补充剂,在此基础上对照组患者予以鲑鱼降钙素鼻喷剂,试验组患者予以唑来膦酸注射液,疗程均为1年。比较两组患者临床疗效,治疗前后骨密度(BMD),血清骨碱性磷酸酶(BAP)、血清I型胶原C端肽(CTX)水平及不良反应发生情况。结果两组患者治疗前BMD比较差异无显著性(P>0.05);治疗后两组患者BMD均高于治疗前(P<0.05),试验组明显高于对照组(P<0.05)。试验组患者治疗总有效率明显高于对照组(P<0.05)。两组患者治疗后BAP水平均较治疗前升高,CTX水

  11. Observation of clinical effects of salmon calcitonin acetate in treatment of 76 elderly patients with osteoporosis%鲑鱼降钙素治疗76例老年骨质疏松症的临床效果观察

    Institute of Scientific and Technical Information of China (English)

    张爱国; 田晓伟

    2014-01-01

    目的:分析对老年骨质疏松症患者应用鲑鱼降钙素进行治疗的临床效果。方法选取我院近3年收治的老年骨质疏松症患者76例,随机将其分为A、B两组,其中A组应用鲑鱼降钙素联合钙尔奇D进行治疗,B组应用钙尔奇D进行治疗,对比A、B两组患者的临床效果、骨密度、疼痛改善情况以及生活质量。结果 A组患者的总有率以及疼痛缓解率均明显高于B组,其差异存在统计学意义(P<0.05),此外,A组患者经过治疗后,其骨密度明显增加,差异存在统计学意义(P<0.05),而B组患者在治疗前后,骨密度没发生多大的变化。结论对老年骨质疏松症患者临床应用鲑鱼降钙素治疗,不仅可以取得良好的效果,还能够缓解患者疼痛情况,并且提高患者的生活与工作质量,具有很多优势,值得各大医院临床推广使用。%Objective To analyze the clinical effects of salmon calcitonin acetate in the treatment of elderly patients with osteoporosis.MethodsSeventy-six elderly patients with osteoporosis who had been treated in our hospital in the recent 3 years were selected and randomly divided into group A and group B. Group A received salmon calcitonin acetate combined with caltrate D treatment; Group B received caltrate D treatment.The clinical effects,bone density,pain improvement situation and quality of life of the two groups of patients were compared.ResultsGroup A had significantly higher total effective rate and pain remission rate than group B,with statistically significant differences(P<0.05).In addition,after treatment, the bone density of group A increased significantly,with statistical significance (P<0.05); but the bone density of group B did not change obviously after treatment.ConclusionThe clinical application of salmon calcitonin acetate treatmnet in the elderly patients with osteoporosis can not only obtain good effects,but also relieve pain and improve the

  12. Postural reduction combined with perioperative salmon calcitonin and delayed percutaneous kyphoplasty for the treatment of osteoporotic lumbar burst fractures%体位复位、围手术期鲑鱼降钙素及延期经皮椎体后凸成形术治疗骨质疏松性腰椎爆裂骨折

    Institute of Scientific and Technical Information of China (English)

    陈明; 喻恒锋; 韩智敏; 李志云; 蔡强强; 闵燕

    2013-01-01

    目的:探讨体位复位、围手术期鲑鱼降钙素及延期经皮椎体后凸成形术( PKP)治疗骨质疏松性腰椎爆裂骨折的可行性及疗效。方法自2008年12月~2012年12月,应用体位复位、围手术期鲑鱼降钙素及延期PKP治疗骨质疏松性腰椎爆裂骨折13例。结果本组获随访6~38个月,平均17.8个月。13例均顺利完成手术,末次随访均未发现邻近椎体新发骨折。本组未出现骨水泥渗漏,未对前方大血管造成危害,术后无神经症状及特殊不适。患者疼痛视觉模拟评分( VAS)术后第7天和末次随访时情况较术前明显改善,差异有统计学意义( P <0.01);椎体前缘高度、矢状面 Cobb 角手术前后比较,差异无统计学意义( P >0.05)。结论体位复位、围手术期鲑鱼降钙素及延期PKP治疗骨质疏松性腰椎爆裂骨折,手术创伤小,安全可行。术后伤椎即刻稳定,止痛效果好,患者可早期下床活动,避免常见的卧床并发症。%Objective To explore the feasibility and efficacy of postural reduction combined with perioperative salmon calcitonin and delayed percutaneous kyphoplasty ( DPKP) for the treatment of osteoporotic lumbar burst fractures .Methods Thirteen patients with osteoporotic lumbar burst fractures , who were treated with postural reduction combined with perioperative salmon calcitonin and DPKP from December 2008 to December 2012, were selected.Results The follow-up of all the patients ranged from 6 to 38 months, with an average of 17.8 months.The operations of all these 13 patients were successful , and no new fractures of adjacent vertebral bodies were observed at their last follow-up.Neither leakage of bone cement , injury of front major vessels , nor postoperative neurological symptoms and discomfort were observed in all these patients .The pain visual analogue scale ( VAS) at the 7 th day after the operation and at the last follow-up was

  13. Curative effect observation of PFNA combined with salmon calcitonin on unstable intertrochanteric fractures in elderly%高龄患者防旋近段股骨髓内钉固定术后使用降钙素的疗效观察

    Institute of Scientific and Technical Information of China (English)

    邹菁; 黄东永; 黄远源; 陈敏; 黄仕光; 王友洛

    2016-01-01

    Objective To observe the effect of proximal femoral nail anti-rotation(PFNA)combined with salmon calcitonin for the treatment of unstable intertrochanteric fractures in the elderly.Methods A total of 90 elderly patients with unstable intertrochanteric frac-tures were randomly divided into group A,group B and group C(30 cases in each group).Patients in group A received open reduction with DHS,patients in group B got closed reduction with PFNA,and patients in group C received operation as group B but combined with salmon calcitonin after the operation.The intraoperative and postoperative stuation of three groups were compared.Results The intraoperative and postoperative stuation of group B was better than those of group A,the time of weight-bearing exercise and fracture healing in group C was shorter than those of group B(t =4.42;t =5.0,P <0.05).The group B had a less complication than group A(χ2 =7.03,P <0.05).Con-clusion The PFNA has a good restoration effect with shorter operative time,less bleeding and lower complication rate.And combined with the salmon calcitonin,which can shorten the time of recovery.%目的:探讨闭合复位防旋近段股骨髓内钉内固定联合术后早期使用降钙素治疗高龄不稳定型股骨转子间骨折的疗效。方法选取90例高龄不稳定性股骨转子骨折患者,按手术方法分为 A、B、C 组(每组30例),分别给予切开复位动力髋螺钉(DHS)髓外固定、闭合复位防旋近段骨髓内钉(PFNA)内固定和闭合复位 PFNA +鲑鱼降钙素治疗,观察比较3组术中情况、术后恢复情况和术后并发症情况。结果在术中情况及术后恢复上 B 组比 A 组有优势;而 C 组相对于 B 组,其开始负重锻炼的时间和骨折愈合时间显著较短(t =4.42、5.0,P <0.05);B 组术后并发症发生显著少于 A 组(χ2=7.03,P <0.05)。结论闭合复位 PFNA 内固定能够以较低的术后并发症发生率、较小

  14. Clinical Research of PKP Combined with Salmon Calcitonin in the Treatment of Osteoporotic Vertebral Compression Fractures%PKP联合鲑鱼降钙素治疗老年骨质疏松性椎体压缩骨折的临床研究

    Institute of Scientific and Technical Information of China (English)

    佟向阳; 戴勇; 马立武; 杨效宁

    2015-01-01

    目的:观察经皮椎体后凸成形术(percutane⁃ous kyphoplasty, PKP)联合鲑鱼降钙素治疗老年骨质疏松性椎体压缩骨折的疗效。方法:患者行PKP术后随机分为两组:对照组每日口服碳酸钙D3;治疗组术后予以鲑鱼降钙素和碳酸钙D3联合治疗。分别在术前、术后3d及6个月采用疼痛视觉模拟评分(visual analog scale,VAS)评分、活动能力评分及术后6个月患者伤椎高度丢失、邻近椎体骨折情况来评估两组治疗效果。结果:两组患者术后疼痛均有明显缓解,但与对照组相比,治疗组在术后6个月VAS评分和活动能力评分降低更为明显,患者伤椎高度丢失明显减轻,邻近椎体骨折显著减少,且差异有统计学意义(P均<0.05)。结论:PKP联合鲑鱼降钙素治疗骨质疏松性椎体压缩骨折在缓解疼痛、增强活动能力、减少伤椎高度丢失和邻近椎体骨折方面具有更好的疗效,值得临床推广。%Objective:Observation on therapeutic effects of percutaneous kyphoplasty (PKP) combined with salmon calcito-nin in the treatment of osteoporotic vertebral compression frac-tures. Methods:Patients with PKP were randomly divided into two groups: the control group daily took calcium carbonate D3 orally; the treatment group was treated with salmon calcitonin and calcium carbonate D3. Visual analog scale (VAS) score, ac-tivity score, the vertebral height loss and adjacent vertebral frac-ture were used to evaluate the clinical therapeutic effects of the two groups before operation, 3d and 6 months after surgery. Re-sults:Two groups of patients with pain were significantly re-lieved. But compared with the control group, VAS score, activity score, vertebral height loss and adjacent vertebral fracture were significantly reduced of the treatment group at 6 months after surgery. The difference were statistically significant (all P<0.05). Conclusion:Treating osteoporotic vertebral compression fractures

  15. Effect of Salmon calcitonin combined with expandable pedicle screw internal fixation system in the treatment of senile osteoporotic thoracolumbar fractures%鲑鱼降钙素联合EPS治疗骨质疏松性胸腰椎骨折的疗效

    Institute of Scientific and Technical Information of China (English)

    樊勇; 桑宏勋; 漆伟; 贺伍儿; 张扬; 雷伟

    2013-01-01

    Objective To investigate the clinical effect of salmon calcitonin combined with expandable pedicle screw ( EPS) internal fixation system in the treatment of senile osteoporotic thoracolumbar fractures. Methods A retrospective analysis was earned out in 78 cases of senile osteoporotic thoracolumbar fractures treating with salmon calcitonin combined expandable pedicle screw internal fixation system from January 2008 to January 2010. Patients were observed before and after treatment. Results The anterior and posterior height of vertebral body after operation were significantly higher than the preoperative ones, respectively ( P < 0. 05 ). The postoperative Cobb ' s angle was significantly lower than the preoperative one ( P < 0. 05 ). Postoperative VAS score and JOA score and BMD were significantly better than preoperative ones (P < 0. 05 ). Conclusion For senile osteoporotic thoracolumbar fractures, the salmon calcitonin combined with expandable pedicle screw internal fixation system has a good clinical effect. The method has the advantages of simple operation, rapid postoperative recovery, high stability, promote bone healing, and the clinical application.%目的 探讨鲑鱼降钙素联合膨胀式椎弓根螺钉(EPS)内固定系统治疗老年骨质疏松性胸腰椎骨折的临床疗效.方法 2008年1月~2010年1月,78例老年骨质疏松性胸腰椎骨折患者在我院采用鲑鱼降钙素联合膨胀式椎弓根螺钉内固定系统进行治疗.观察治疗前后的患者情况.结果 通过治疗后的分析,患者术后的椎体前缘高度和椎体后缘高度均明显的高于术前的患者的椎体前缘高度和椎体后缘高度,数据比较具有显著的差异(P<0.05);术后的Cobb's角度明显的低于术前的Cobb's角度,数据的比较具有显著性的差异(P<0.05).术后的VAS评分和JOA评分以及BMD均明显的优于手术治疗前,数据比较具有显著的差异(P<0.05).结论 对于老年骨质疏松性胸腰椎骨折

  16. 鲑鱼降钙素联合低钙透析液治疗血透患者高磷血症的临床研究%Clinical study of low calcium dialysate combined with salmon calcitonin in the treatment of hyperphosphatemia in hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    关毅标

    2014-01-01

    Objective To evaluate the effect of low calcium dialysate combined with salmon calcitonin in the treatment of hyper-phosphatemia in hemodialysis patients.Methods Forty hemodialysis patients with hyperphosphaemia were randomly divided into the treatment group (n=19) and the control group (n=21).Patients in the control group were treated with low calcium dialysate (with Ca+ concentration of 1.5 mmo1 )combined with calcium carbonate as well as vitamin D3 ,while those in the treatment group were treated with low calcium dialysate (with Ca2+ concentration of 1.25 mmo1)combined with salmon calcitonin,as well as calcium carbonate and vitamin D3.The Ca,phosphate product and iPTH were detected three and six months after treatment.Results In the control group, the serum phosphate and iPTH was significantly increased after treatment ( P0.05). Conclusion For hemodialysis patients with hyperphosphatemia ,low calcium dialysate combined with salmon calcitonin can effectively reduce serum phosphate level with no effect on iPTH.%目的:探讨低钙透析液联合鲑鱼降钙素对维持血透(Maintenance hemodialysis, MHD)患者高磷血症的影响。方法选取我院近期维持性血液透析患者中高磷血症患者40例,采用随机数字表法分为对照组21例,给予常规钙透析液+活性维生素D3治疗;试验组19例,给予低钙透析液联合鲑鱼降钙素注射液治疗。观察两组患者治疗后第3、6个月时血清钙磷代谢等指标有无差别。结果对照组治疗后血清钙较治疗前无明显变化(P>0.05),但血磷和甲状旁腺激素(iPTH)较透析前明显增加(P<0.05);试验组治疗后血清钙、iPTH无明显变化(P>0.05),血磷显著降低(P<0.05)。结论鲑鱼降钙素联合低钙透析液治疗MHD能有效降低患者血磷水平且不致影响iPTH。

  17. Analysis of the effect of salmon calcitonin combined with percutaneous vertebroplasty in the treatment of senile vertebral compression fractures%鲑降钙素联合经皮椎体成形术治疗老年椎体压缩骨折的疗效分析

    Institute of Scientific and Technical Information of China (English)

    袁俊

    2014-01-01

    目的:探讨鲑降钙素联合经皮椎体成形术治疗老年椎体压缩性骨折的临床疗效。方法:2010年1月-2013年1月收治脊柱压缩骨折老年患者46例,随机分为两组,每组23例,对照组采用经皮椎体成形术治疗,观察组在对照组基础上于围手术期加用鲑降钙素治疗。比较两组的住院费用、术后下地时间和骨密度差异,术后采用JOA评分系统评价脊柱功能,并观察不良反应的发生情况。结果:两组住院费用、术后下地时间和JOA评分差异无统计学意义(P>0.05)。随访3个月后,观察组骨密度(0.798±0.110) g/cm3,对照组(0.756±0.112) g/cm3,其差异有统计学意义(P<0.05)。观察组1例出现消化道反应,发生率4.3%,经对症治疗后缓解,两组差异无统计学意义。结论:在老年压缩性骨折采用鲑降钙素联合经皮椎体成形术治疗可提高骨密度,降低再发骨折的风险,同时不增加不良反应的发生率。%To investigate the clinical efficacy of salmon calcitonin combined with percutaneous vertebroplasty in the treatment of senile vertebral compression fractures.Methods:46 cases with vertebral compression fractures in elderly were selected from January 2010 to January 2013.They were randomLy divided into two groups with 23 cases in each.The control group were given percutaneous vertebroplasty treatment,and the observation group were given salmon calcitonin in the peri operation period with on the basis of the control group.We compared the hospitalization,postoperative ambulation time and bone mineral density differences of two groups.We used the JOA scoring system to evaluate the spinal function after operation,and observed the adverse reactions.Results:There were no statistically significant differences in the postoperative ambulation time,the JOA score and hospitalization expenses of the two groups(P>0.05).After 3 months of follow-up,the bone mineral density of the control

  18. Based on the Salmon Calcitonin Treatment the Clinical Effect of the Treatment of Osteoporosis in Older Men%基于鲑鱼降钙素治疗老年男性骨质疏松症的临床疗效研究

    Institute of Scientific and Technical Information of China (English)

    李照霞

    2015-01-01

    目的:分析鲑鱼降钙素对于老年男性骨质疏松症(OP)进行治疗的疗效。方法选择68例 OP 病患进行本组研究,病患皆为老年男性,将其分作参照组与治疗组各34例,参照组选用常规的钙片治疗,而治疗组选用鲑鱼降钙素治疗,对比两组的临床疗效。结果治疗后,治疗组的骨密度明显比治疗前与参照组高(P <0.05);治疗组的疼痛缓解情况也明显比参照组好(P <0.05)。结论对于 OP 老年男性患者采用鲑鱼降钙素治疗疗效显著,可有效改善骨密度与缓解骨疼痛,并抑制骨的吸收与促进骨的形成。%Objective To analyze the salmon calcitonin forosteoporosis in aged males (OP) of the efficacy of the treatment. Methods 68 cases of OP patients in this group of patients, for older men, be classified as a reference group and treatment group with 34 cases in each group, the reference group using routine of calcium treatment, while the treatment group used the salmoncalcitonin treatment, compared two groups of clinical curative effects. Results After the treatment, the bone density of treatment group is more obvious than before treatment with high referencegroup (P < 0.05); the treatment group also obvious pain relief than the reference group (P < 0.05). Conclusion For the elderly male patients with OP by salmon calcitonin treatment has obvious curative effect, can effectively improve the bone density and relieve bone pain, and inhibit bone absorption and promoting bone formation.

  19. Effects of Simo decoction on calcitonin gene-related peptide and ghrelin in diabetic rats%四磨汤对糖尿病大鼠降钙素基因相关肽及饥饿素的影响

    Institute of Scientific and Technical Information of China (English)

    戴迟兵; 刘娜; 钱伟; 侯晓华

    2012-01-01

    Objective To investigate the effects of Simo decoction on ghrelin and calcitonin gene-related peptide (CGRP) in diabetic rats.Methods A total of 48 SD rats were divided into healthy control group,diabetes group (DM),DM treated with low dose Simo decoction group (DMTL),DM treated with medium dose Simo decoction group (DM-TM),DM treated with high dose Simo decoction group (DM-TH) and DM prevented with medium dose Simo decoction group (DMPM) ; there were eight rats in each group.The rats of DM group and other intervention groups were intraperitoneally injected with 1% streptozotoein (STZ) to establish the model.The rats of healthy control group were injected with solvent.At eight weeks after the model successfully established,the rats of each intervention group were gavaged with low dose of Simo decoction (0.15 ml · kg-1 · d-1 ),medium dose of Simo decoction (1.5 ml · kg-1 · d-1 ) and high dose of Simo decoction (3.0 ml · kg-1 ·d-1 ) for two weeks; the rats of control group and DM groups were gavaged with equal volume of 0.9%NaCl.The rats of DM-PM group were gavaged with Simo decoction at 1.5 ml · kg-1 · d-1 for 10 weeks after the model successfully established.Rats were sacrificed at the end of drug intervention and gastric antrum tissues were dissociated for detecting the expression of ghrelin and CGRP by real time polymerase chain reaction (PCR).The data were analyzed by one way ANOVA and t test.Results There was no significant difference in ghrelin expression at mRNA level in gastric antrum tissues between diabetic rats and control group.However after intervened by low dose and medium dose of Simo decoction,the ghrelin expression increased (1.45 ± 0.34,1.87 ± 0.68 compared with 0.87 ±0.28,Dunnett's T3 test,P<0.05).There was no effects of high dose Simo decoction on the expression of ghrelin in diabetic rats.There was no significant difference in ghrelin between DM-TM and DM-PM.The expression of CGRP at mRNA level in gastric antrum tissues of

  20. Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Schifter, S; Møller, S

    2000-01-01

    circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child-Turcotte...... control (12.1 v 6.9 pmol/L, P Turcotte score was found (P

  1. Study of Calcitonin and Calcitonin Gene-related Peptide in Patients with Medullary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Gao; Yang Yu; Shuling Li; Benyi Xu; Baocun Sun; Jingzu Liu

    2005-01-01

    OBJECTIVE To provide a basis for treatment and prognosis for MTC patients by investigating CT and CGRP.METHODS Fifty-eight cases of MTC were selected and the relationship between the CT levels and metastasis was investigated. An immunohistochemical method was used to detect the expression of CT and CGRP in the 58 samples of MTC tissues. The CT and CGRP of new MTC inpatients were measured before operation and in the first few days after operation using a radioimmunoassy.RESULTS 1 ) The metastatic rate of cervical lymph nodes was a significantly different between the normal serum CT group and the elevated group (P<0.01). 2) The rate of residual tumor was significantly different between the normal serum CT group one month after operation and the elevated group at the same period (P<0.01). 3) In the immunohistochemical study we found the positive rate of CT was about 98%, and the CGRP was 87.8%. 4) Part of the patients had an elevated CGRP level while CT levels were normal. 5) The serum CT levels dropped to a stable range one week after operation.CONCLUSION The CT levels are a useful index to evaluate the probability of cervical lymph node metastasis and the efficacy of surgical treatment.Measurement of the serum CGRP is an aid for the diagnosis of MTC,especially for those patients whose preoperative CT levels are normal.

  2. Effect of Salmon calcitonin on metabolism of Blood 89 Sr and combined treatment with 89 SrCl2 in Cancer Patients with Bone Metastases%鲑鱼降钙素联合氯化锶对恶性肿瘤骨转移性骨痛及对血锶代谢影响的临床观察

    Institute of Scientific and Technical Information of China (English)

    张云平; 李仰康; 刘阳晨

    2016-01-01

    目的:观察降钙素联合氯化89锶治疗恶性肿瘤骨转移痛的疗效,判断降钙素在治疗中的作用。方法73名恶性肿瘤骨转移病例分为,联合组29例患者,用氯化89锶(3-4 mci iv)+降钙素(100IU 喷鼻1次/天);氯化89锶治疗组25例患者,用氯化89锶(3-4mci iv)和对照组19例患者,不同意锶治疗的肿瘤骨转移病人(其它方法治疗骨痛),观察镇痛总有效率并以火焰原子吸收法测定全血锶含量,随诊12个月,2例死亡退出观察。结果联合治疗组疗效高峰出现在第一个月,总有效率96.4%(27/28);绿化锶组疗效高峰出现在第一个月,总有效率83.33%(20/24),两治疗组比较差异显著(P <0.01);联合治疗组血锶水35.5μg/L,明显低于氯化89锶组和对照组(P <0.05)。氯化锶组血锶水平39.8μg/L,与对照组血锶含量无显著性差异(P >0.05)。结论降钙素联合氯化89锶镇痛效果显著好于氯化锶组(P <0.01);降钙素促进骨转移灶对89锶吸收,降钙素可以作为氯化89锶的增效剂。%Objective To observe the effect of salmon calcitonin on concentration of blood 89 Sr and efficacy of treat-ment combined with 89 SrCl2 in blood of cancer patients with bone metastases.Methods There were 73 cases cancer pa-tients with bone metastases selected from October 2013 to October 2014.29 cases were treated with 89 SrCl2 (4mci iv) combined with salmon calcitonin;25 cases were treated with 89 SrCl2 and the 19 with other therapy.The total response rate and the pain level was estimated,the 89 Sr concentrations in blood were measured by Flame atomic absorption spec-trophotometer.Two patients withdrawn due to death and all patients were followed up one year.Results The 28 pa-tients were treated with 89 SrCl2 (4mci iv)combined with salmon calcitonin,the pain levels were relieved in all patients except one (96.4%),89 SrCl2 group

  3. Construction of a Ribosomal DNA Multi-Copy Integration Vector for Saccharomyces cerevisiae Expressing Salmon Calcitonin%以rDNA为同源重组位点酵母表达鲑鱼降钙素基因多拷贝整合载体的构建

    Institute of Scientific and Technical Information of China (English)

    姜勇; 张学成; 孙平楠; 陈云松

    2009-01-01

    根据酵母整合质粒的设计要求,PCR扩增2.2 kb rDNA片段,导入酿酒酵母(Saccharomyces cerevisiae)整合载体pYD1中,设计并合成适合在酵母中表达的鲑鱼降钙素(Salmon Calcitonin),以此为目标基因,构建适合酿酒酵母多拷贝整合的表达载体p-r-sCT.通过载体p-r-sCT引入到酿酒酵母菌株EBY100中,得到酵母重组菌株yAGA2-r-sCT.流式细胞检测结果表明,目标基因鲑鱼降钙素在重组菌株的yAGA2-r-sCT中得到了表达,实现了外源基因在酿酒酵母菌株中的稳定表达.

  4. Effects of salmon calcitonin on gene and protein expression of OPG and RANKL in bone marrow cells from ovariectomized rats%鲑鱼降钙素对去卵巢大鼠骨髓细胞OPG、RANKL基因和蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    王键; 魏劲松; 龚颜; 曾荣

    2013-01-01

    [目的]观察鲑鱼降钙素(sCT)对去卵巢大鼠骨密度(BMD)、血清Ⅰ型胶原交联羧基末端肽(ICTP)变化的影响,以及骨髓细胞骨保护素(OPG)和核因子κB受体活化因子配体(RANKL)的基因表达和两者在胫骨骨骺端蛋白含量的变化.[方法]取3个月龄雌性SD大鼠24只,随机平均分3组:假手术组(Sham)、鲑鱼降钙素处理组(sCT)、安慰剂组(OVX).采用双侧卵巢切除术复制骨质疏松大鼠模型.术后2周CT组予鲑鱼降钙素皮下注射12周,应用双能X线吸收仪法(DXA)测BMD,ELISA法测量血清ICTP浓度,qRT-PCR法定量骨髓细胞OPG和RANKL的mRNA表达量,免疫组织化学染色法测定胫骨干骺端OPG和RANKL蛋白表达量.[结果]与OVX组比较,sCT组的腰椎BMD上升显著(P<0.05),但股骨BMD改变不明显(P>0.05);血清ICTP含量显著降低(P<0.05);骨髓细胞RANKL的mRNA表达量变化不大(P>0.05),但OPG的mRNA表达量升高(P<0.05),OPG/RANKL的比率升高(P<0.05);胫骨干骺端也呈现出RANKL蛋白改变不明显(P>0.05),而OPG的蛋白分泌增加(P<0.05),从而OPG/RANKL的比率高于OVX组(P<0.05)的现象.[结论]降钙素可以预防腰椎BMD的丢失,降低血清ICTP水平,在体内可能主要通过上调OPG的mRNA表达和蛋白分泌,影响OPG/RANKL/RANK系统,影响破骨细胞功能,抑制骨吸收,进而达到预防绝经后骨质疏松的目的.%[Objective] To observe the effects of salmon calcitonin on bone mineral density (BMD) , serum procollagen type I collagen cross - linked telopeptide ( ICTP) , gene expression of receptor activator of NF - tcB ligand ( RANKL) and os-teopretegerin (OPG) in bone marrow cells, as well as protein expression of OPG and RANKL in tibial metaphysis from ovariec-tomized rats. [Methods] Twenty -four healthy female SD rats, 3 months old, were randomly divided into three groups ( 8 in each) : the sham -operated control group (Sham) , the ovariectomized group (OVX) and the salmon calcitonin treated group

  5. Clinical observation of Qianggu capsules combined with salmon calcitonin injection in the treatment of osteoporotic compression fractures in the elderly%强骨胶囊联合鲑鱼降钙素针剂辅助治疗老年骨质疏松性压缩骨折临床观察

    Institute of Scientific and Technical Information of China (English)

    杨国志; 李振武; 尹锐峰; 李志安

    2014-01-01

    Objective To investigate the clinical efficacy and the influence of Qianggu capsules combined with salmon calcitonin injection in the treatment of osteoporotic compression fractures in the elderly.Methods Two hundred and fifty-seven patients with osteoporotic thoracolumbar vertebral fractures were randomly divided into 3 groups.Patients in the observation group took oral medication of Qianggu capsules, combined with an intramuscular injection of salmon calcitonin injection.Patients in control group I took oral medication of Qianggu capsules only, and patients in control group II were intramuscularly injected with salmon calcitonin injection only.The clinical efficacy was observed.Bone mineral density (BMD) and the serum levels of osteocalcin (BGP), calcium, phosphorus, and alkaline phosphatase were detected before and after the treatment.Urinary contents of calcium, hydroxyproline, and creatinine were also detected.The calcium/creatinine ratio and hydroxyproline/creatinine ratio in urine were calculated.Results The total effective rate in the observation group was significantly higher than that in the control group I and the control group II ( P 0.05).After the treatment, no significant changes of serum phosphorus and urinary calcium/creatinine in 3 groups were observed, and no significant difference among 3 groups was observed (P>0.05).Conclusion The efficacy of Qianggu capsules combined with salmon calcitonin in the treatment of osteoporotic fractures in the elderly is assured.It can relieve pain, promote fracture healing, reduce the recurrence of fractures, and has no obvious adverse reaction.%目的:探讨强骨胶囊联合鲑鱼降钙素针剂辅助治疗老年骨质疏松性压缩骨折临床疗效及影响。方法257例胸腰椎骨质疏松性骨折患者随机分为3组,观察组口服强骨胶囊同时肌肉注射鲑鱼降钙素注射液,对照I组口服强骨胶囊,对照Ⅱ组肌肉注射鲑鱼降钙素针剂。观察临床疗效,测定治

  6. 降钙素基因相关肽和BIBN4096BS对麻醉大鼠心肌缺血的作用%Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Mei WU; Pieter A van ZWIETEN; Henri N DOODS

    2001-01-01

    AIM: The cardioprotective effect of calcitonin gene related peptide (CGRP) was investigated in an ischemia rat model. METHODS: Ischemia-reperfusion injury was provoked by 60 min left main coronary artery occlu sion followed by 60 min of reperfusion in anesthetized rats. The transverse slices of ventricles were stained by 2,3,5-triphenyltetrazolium chloride to determine the in farct area. Plasma creatine phosphokinase levels were determined by means of a creatine phosphokinase (CPK) kit. A radioimmunoassay was used to determine plasma CGRP levels. RESULTS: Intravenous infusion of CGRP (1 nmol· kg- 1·h-1) 10 min before occlusion until the end of reperfusion reduced infarct size by 89 % ± 5 %. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase. Infusion of the same dose of CGRP commehcing from the start of reperfusion until its end induced a 40 % ± 3 % reduction of the infarct size. The cardioprotective effects of CGRP were blocked by the novel CGRP antagonist BIBN4096BS (20 nmol· kg-1 · h-1 ). Although cardiac ischemia resulted in an almost 50 % increase in plasma CGRP levels in blood sampled from right cardiac ventri cle, intravenous infusion of the CGRP antagonist BIBN4096BS before occlusion until the end of reperfusion had no statistically significant effect on the infarct size. CONCLUSION: The present study demonstrates that CGRP is a potent myocardial protective substance.

  7. Effect of PFNA fixation combined with salmon calcitonin in the treatment of senile femoral intertrochanteric fracture and the influence on bone mineral density%PFNA固定联合鲑鱼降钙素治疗老年股骨粗隆间骨折的效果及对骨密度的影响

    Institute of Scientific and Technical Information of China (English)

    应挺君

    2015-01-01

    目的:研究股骨近端防旋髓内钉(PFNA)内固定与鲑鱼降钙素(SCT)联合治疗老年股骨粗隆间骨折的效果及其对骨密度(BMD)的影响。方法将老年股骨粗隆间骨折患者82例随机分成SCT组与对照组,各41例。两组均行PFNA内固定术,对照组术后应用钙尔奇D600,SCT组在对照组的基础上加用SCT,比较两组的手术时间、术中出血量、术后住院时间及骨折愈合时间等手术指标,随访比较两组手术前后Harris评分、视觉模拟评分(VAS)、BMD以及髋关节功能。结果 SCT组的住院时间与骨折愈合时间明显短于对照组,VAS降低较对照组明显(P0.05)。结论 PFNA内固定治疗老年股骨粗隆间骨折具有显著效果,配合SCT治疗可提高BMD,促进骨折愈合,改善患者的生活质量。%Objective To investigate the efficacy of PFNA fixation combined with salmon calcitonin (SCT) in the treat-ment of senile femoral intertrochanteric fracture and the effects on bone mineral density (BMD). Methods 82 cases of senile femoral intertrochanteric fracture patients were randomly divided into SCT group and control group, with 41 cas-es in each group. Both groups underwent PFNA fixation, the control group received caltrate D600 treatment, SCT group received SCT on the basis of the control group, the surgical indexes such as operative time, blood loss, hospitai stay time and bone healing time of the two groups were compared, the Harris score, VAS score, BMD and hip function be-fore and after surgery of the two groups were followed and compared. Results The hospital stay time and bone healing time in SCT group was significantly shorter than the control group, and the VAS reduction was significantly better than the control group (P0.05). Conclusion PFNA fixation in the treatment of senile femoral intertrochanteric fracture has a signif-icant effect, combined with salmon calcitonin can improve BMD, promote healing and improve

  8. Control Study of Treatment of Salmon Calcitonin for Hip Joint Fracture on Postoperative Affect of Determination of Ultrasound Bone Density%鲑鱼降钙素治疗对髋关节骨折术后患者超声骨密度测定影响的对照研究

    Institute of Scientific and Technical Information of China (English)

    王志; 张秀花; 陈庆法; 蒋娴; 倪宏伟

    2015-01-01

    目的结探讨鲑鱼降钙素治疗对髋关节骨折术后患者超声骨密度测定的影响。方法选取2013年1月~2015年1月来我院进行诊治的髋关节骨折患者60例,随机分为对照组和观察组,每组30例,对照组给予常规和促进骨折愈合治疗,观察组在此基础上加用鲑鱼降钙素喷鼻剂治疗,比较两组患者治疗前后超声骨密度测定结果。结果治疗前,两组患者使用超声骨密度仪测定骨密度,结果相比无显著性差异(>0.05);治疗后,观察组患者超声传播速度、骨硬度指数、超声波振幅衰减值均明显增高,与对照组和同组治疗前相比,差异具有统计学意义(0.05); After treatment, the ultrasonic velocity, bone stif ness index and ultrasonic amplitude at enuation' value al obviously increased, compared with control group and the same group before treatment, the dif erence had statistical significance ( <0.05).Conclusion Salmon calcitonin could increase the bone density of patients who with hip joint fracture, and prevent bone lose in patients with fracture.

  9. Clinical Effect of Anti Oxidants Combined with Salmon Calcitonin in the Treatment of Diabetic Osteoporosis%抗氧化剂联合鲑鱼降钙素治疗糖尿病性骨质疏松患者的临床疗效

    Institute of Scientific and Technical Information of China (English)

    郭淑玲

    2016-01-01

    目的:探讨抗氧化剂联合鲑鱼降钙素治疗糖尿病性骨质疏松患者的临床疗效。方法选取2013年1月至2015年1月临汾市骨科医院收治的121例糖尿病性骨质疏松患者作为研究对象,采用随机数字表法将其分为对照组(60例)与观察组(61例)。对照组患者肌内注射鲑鱼降钙素注射液,同时口服碳酸钙D3片,观察组患者在对照组基础上采用抗氧化剂硫辛酸进行治疗,比较两组患者治疗前后骨代谢及骨转化情况、血糖及疼痛程度、自我效能量表评分。结果治疗后,观察组患者的Ⅰ型胶原交联羧基末端肽(CTX-1)明显低于对照组,碱性磷酸酶(ALP)、骨钙素(BGP)均明显高于对照组,差异均有统计学意义(均P<0.05);治疗后,观察组患者的空腹血糖(FBG)、餐后2 h血糖(2hPBG)及疼痛视觉模拟量表(VAS)评分均明显低于对照组,差异均有统计学意义(均P<0.05);治疗后,观察组患者的运动效能、摄钙效能评分及总分均明显高于对照组,差异均有统计学意义(均P<0.05)。结论在抗氧化治疗基础上应用鲑鱼降钙素可有效改善糖尿病性骨质疏松患者骨代谢,减轻疼痛,血糖控制效果理想,是提高临床疗效的重要方法。%Objective To investigate the clinical effect of anti oxidants combined with salmon calcitonin in the treatment of diabetic osteoporosis patients.Methods From January 2013 to January 2015,121 patients with diabetic osteoporosis were treated in the Department of orthopedics of Linfen city as the research object,and were randomly divided into control group(60 cases) and observation group (61 cases).Control group patients with intramuscular injection of salmon calcitonin injection,and oral calcium carbonate D3 tablets were observed group of patients in the control group on the basis of the antioxidants lipoic acid treatment,were compared between the two

  10. Clinical study of low calcium dialysate combined with salmon calcitonin in the treatment of hyperphosphatemia in hemodialysis patients%低钙透析液联合鲑鱼降钙素治疗血透患者高磷血症的临床研究

    Institute of Scientific and Technical Information of China (English)

    周礼

    2012-01-01

    目的 观察低钙透析液联合鲑鱼降钙素对血透患者高磷血症的影响.方法 选取近期维持性血液透析患者中高磷血症患者40例,随机分为对照组和实验组各20例,对照组用正常钙透析液(钙离子浓度为1.5 mmol)配合碳酸钙和活性维生素D3治疗.实验组用低钙透析液(钙离子浓度为1.25 mmol)联合鲑鱼降钙素注射液同时服用碳酸钙和活性维生素D3治疗.观察治疗后第1、3、6个月时患者的血钙、血磷、钙磷乘积以及全段甲状旁腺激的水平.结果 对照组透析后,与透析1个月比较,6个月血钙、血磷、钙磷乘积均轻度增高(P<0.05),而iPTH水平无明显变化(P>0.05);实验组透析后,与透析1个月比较,3个月血钙、血磷、钙磷乘积均轻度减低(P<0.05),而iPTH水平明显增高(P<0.05);6个月血钙、血磷、钙磷乘积均轻度减低(P<0.05),而iPTH水平趋于稳定(P>0.05);与对照组比较,实验组患者3个月血磷、钙磷乘积均轻度减低(P<0.05),而iPTH水平明显增高(P<0.05);实验组患者6个月血磷、钙磷乘积、iPTH均轻度减低(P<0.05).结论 低钙透析液联合鲑鱼降钙素治疗HD患者能有效的维持血磷水平,降低钙磷乘积,而不致影响iPTH.%Objective To observe the effect of low calcium dialysate combined with salmon calcitonin in the treatment of hyperphosphatemia in hemodialysis patients. Methods Forty hemodialysis patients with hyperphosphatemia were randomly divided into the study group and the control group, each with 20 cases. Patients in the control group were treated with low calcium dialysate (with Ca2+ concentration of 1.5 mmol) combined with calcium carbonate as well as vitamin D3, while those in the study group were treated with low calcium dialysate (with Ca2+ concentration of L25 mmol) combined with salmon calcitonin, as well as calcium carbonate and vitamin D3. The Ca, P, calcium-phosphate product, iPTH were detected one, three, and six

  11. Observation on Efficacy of Atorvastatin Combined with Salmon Calcitonin, Caltrate D3, Alendronate in Treatment of Senile Osteoporosis%阿托伐他汀联合鲑鱼降钙素、碳酸钙D3、阿伦磷酸钠治疗老年骨质疏松症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    钱雪丰; 曹平; 刘拴; 张明勇

    2016-01-01

    OBJECTIVE:To probe into the clinical efficacy of atorvastatin combined with salmon calcitonin , caltrate D3 , alendronate in treatment of senile osteoporosis .METHODS:280 patients with senile osteoporosis admitted into Tianyou Hospital Affiliated to Wuhan University of Science and Technology were selected to be divided into observation group and control group via the random number table , with 140 cases in each .The control group were treated with caltrate D 3 combined with alendronate , and the observation group additionally received atorvastatin combined with salmon calcitonin based on the control group .The VAS score , clinical efficacy , BMD values and adverse drug reactions were compared between two group of patients .RESULTS: VAS score of two groups after treatment were significantly lower than those of before treatment , and those of the observation group were even lower than those the control group , with statistically significance ( P<0.05 ) .The total efficacy in observation group was 85.71%(120/140), significantly higher than that in control group 68.57%(96/140), with statistically significant difference(P<0.05),lumbar bone mineral density of two groups after treatment were significantly more increased than those of before treatment , and the observation group was increased obviously ,with statistically significance (P<0.05). CONCLUSIONS:The efficacy of atorvastatin combined with salmon calcitonin , caltrate D3 , alendronate in treatment of senile osteoporosis is remarkable , which can improve bone density and relieve pain effectively with high safety .%目的:探讨阿托伐他汀联合鲑鱼降钙素、碳酸钙D3、阿伦磷酸钠治疗老年骨质疏松症患者临床疗效。方法:选取武汉科技大学附属天佑医院收治的老年骨质疏松症患者280例为研究对象,以随机数字表法分为观察组和对照组各140例。对照组患者给予碳酸钙D3联合阿伦磷酸钠,观察组在此基础上加用鲑鱼降钙素及

  12. 鲑鱼降钙素联合碳酸钙D3片治疗绝经妇女桡骨远端骨折的疗效观察%Clinical observation of salmon calcitonin combined with calcium carbonate and vitamin D3 in treatment of distal radius fracture in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    闫博

    2016-01-01

    目的 评估鲑鱼降钙素鼻喷剂联合碳酸钙D3片治疗绝经妇女桡骨远端骨折的临床疗效.方法 选取2012年12月-2014年12月在陕西省核工业二一五医院骨科接受掌侧钢板内固定的桡骨远端骨折绝经妇女59例,所有患者随机分为对照组(26例)和治疗组(33例).对照组口服碳酸钙D3片,1片/次,1次/d.治疗组在对照组治疗基础上给予鲑鱼降钙素鼻喷剂,200 IU/d.两组均连续治疗3个月,并随访6个月.比较视觉模拟评分(VAS)、骨密度值、腕关节功能.结果 治疗3 d、1个月、3个月、随访6个月,两组患者的VAS评分均较治疗前显著降低,同组治疗前后比较差异具有统计学意义(P<0.05);且治疗1、3个月后,治疗组患者的VAS评分改善程度明显优于同期对照组,两组比较差异有统计学意义(P<0.05).治疗3个月、随访6个月,治疗组的骨密度值均较治疗前显著增高,同组治疗前后比较差异具有统计学意义(P<0.05);且治疗组患者的骨密度值改善程度明显优于同期对照组,两组比较差异具有统计学意义(P<0.05).而对照组的几乎没有变化.治疗后,对照组和治疗组患者腕关节功能评分优良率分别为61.5%、87.9%,两组优良率比较差异具有统计学意义(P<0.01).结论 鲑鱼降钙素联合碳酸钙D3片治疗绝经妇女桡骨远端骨折具有较好的疗效,能够增加骨密度,促进腕关节功能恢复,具有一定的临床推广应用价值.%Objective To evaluate the clinical efficacy of Salmon Calcitonin Nasal Spray combined with Calcium Carbonate and Vitamin D3 Tablets in treatment of distal radius fracture in postmenopausal women.Methods Postmenopausal women (59 cases) with distal radius fracture in Department of Bone of No. 215 Hospital of Shaanxi Nuclear Industry from December 2012 to December 2014 were randomly divided into control (26 cases) and treatment (33 cases) groups. The patients in the control group werepo administered with Calcium

  13. Effects of calcium carbonate, vitamin D3 and calcitonin combined with pulsed electromagnetic fields on osteoporosis in elderly women%碳酸钙维生素D3及鲑鱼降钙素联合脉冲电磁场治疗老年女性骨质疏松症的临床观察

    Institute of Scientific and Technical Information of China (English)

    马丽萍; 王剑火; 姜绪防

    2013-01-01

    目的 观察碳酸钙维生素D3及鲑鱼降钙素联合脉冲电磁场治疗老年女性骨质疏松症的疗效.方法 老年女性原发性骨质疏松症96例,随机分为对照组和观察组,每组48例.对照组给予口服碳酸钙维生素D3(每天1片)及降钙素鼻喷剂(每天喷两次,每次120 IU)治疗12个月,观察组在对照组治疗的基础上加用脉冲电磁场治疗8周.治疗前及治疗后第1、2、4、8周分别测定患者视觉模拟疼痛评分(VAS),治疗前及治疗后1年对患者进行腰椎骨密度(BMD)测量.结果 观察组和对照组在治疗前及治疗后1、2、4、8周,VAS评分分别为:(6.7±2.1),(2.6±0.9),(1.8±0.5),(1.4±0.3),(1.1±0.2)和(6.6±2.0),(4.5±1.3),(4.0±1.1),(3.2±1.0),(2.7±0.8).治疗后两组患者的疼痛均能获得减轻,而且治疗时间越长,疼痛减轻越明显,但观察组比对照组疼痛缓解得更快(P<0.01).治疗前观察组和对照组的腰椎BMD分别为:(0.737±0.083)和(0.739±0.083),治疗后1年则分别为(0.793 ±0.082)和(0.791 ±0.081),观察组与对照组比较,BMD差别无统计学意义(P>0.05),而各组治疗前后比较,BMD升高均具有统计学意义(P<0.01).结论 碳酸钙维生素D3及鲑鱼降钙素治疗老年女性骨质疏松症疗效确切,联合短疗程脉冲电磁场治疗对缓解疼痛具有协同作用,但对治疗后1年的腰椎骨密度的增加似乎无影响.%Objective To study effects of calcium carbonate,vitamin D3 and calcitonin combined with short course of pulsed electromagnetic fields on osteoporosis in elderly women.Methods 96 elderly women with primary osteoporosis were randomized to the study group or control group with 48 in each.Patients in control group received calcium carbonate vitamin D3 (1 tablet/day) and calcitonin nasal spray (120 IU,twice daily) for 12 months.On the basis of control treatment,pulsed electromagnetic fields were added on the patients in the study group for 8 weeks.Visual analogue scale (VAS) was

  14. N-三甲基壳聚糖包覆的降钙素脂质体的制备及其体内外黏附性质研究%Study on Preparation of N-trimethyl Chitosan Coated Calcitonin Liposome and Adhesion Properties of It in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    黄爱文; 竹内洋文; 宋洪涛

    2013-01-01

    目的:制备N-三甲基壳聚糖(TMC)包覆的降钙素脂质体,考察其理化性质以及体内外黏附性质.方法:采用两步反应法合成TMC;采用薄膜水化法制备降钙素脂质体,并用TMC对脂质体进行包覆,考察其粒径、多分散系数、Zeta电位、包封率及形态;采用猪胃黏膜蛋白微粒结合法评价TMC脂质体在pH 4.5、6.8时的体外黏附性质;取大鼠12只,随机分为4组,每组3只,采用C6标记法考察TMC脂质体在十二指肠、空肠、回肠上的体内黏附行为.结果:合成的TMC的季铵化度为78.10%;未包覆的降钙素脂质体带有较强的负电荷,包覆TMC后实现了电荷反转.制得的脂质体外观圆整,包覆层明显,粒径为262.9 nm,多分散系数为0.172,Zeta电位为(35.8±1.2) mV,包封率为(89.14±3.1)%.TMC脂质体在pH 4.5、6.8时均与黏蛋白纳米粒发生黏附作用,Zeta电位降低.在大鼠体内,2h时,TMC包覆脂质体大部分黏附在小肠上部,尤其是十二指肠部位,到达回肠部位的脂质体较少;4h时,TMC脂质体在各肠段仍然有黏附,但较2h时明显减弱,并以回肠部位基底侧黏附最多.结论:TMC包覆脂质体具有良好的生物黏附性能,可以作为多肽类药物口服递送的新型载体进一步深入研究.%OBJECTIVE:To prepare N-trimethyl chitosan (TMC) coated calcitonin liposome,and to investigate the physicochemical properties and adhesion properties of it in vitro and in vivo.METHODS:2-step reaction was adopted for the synthesis of TMC; calcitonin liposome was prepared by thin-film hydration method,and the liposomes were coated with TMC; the particle size,polydispersity index,Zeta potential,encapsulation efficiency and form were all investigated; the pig gastric mucosal protein particles combination method was used to evaluate in vitro adhesion properties of TMC liposome with pH of 4.5 and 6.8; 12 wistar rats were randomly divided into 4 groups,with 3 rats in each group; the adhesion behavior of

  15. 鲑鱼降钙素联合唑来膦酸注射液治疗老年原发性骨质疏松症的疗效观察%Efficacy of salmon calcitonin combined with zoledronic acid in treatment of senile primary osteoporosis

    Institute of Scientific and Technical Information of China (English)

    沈小明; 黄成龙; 陈刚; 龚遂良

    2016-01-01

    One hundred and twenty patients with senile primary osteoporosis were enrolled in the study from January 2012 to April 2013,including 41 males and 79 females.Patients were randomly assigned to two groups:60 patients in study group were treated with salmon calcitonin combined with zoledronic acid (salmon calcitonin 50 IU i.m,q.d for 7 d,then 100 IU q.i.d for 7 d,followed by zoledronic acid 5 mg i.v gtt/y);60 cases in control group were treated with alendronate (70 mg p.o/wk).Both groups received the same doses of calcium.Visual analogue scale (VAS) scores were assessed before,and 1,6 and 12 months after treatment,12-Item Short-Form Health Survey (SF-12) and bone mineral density (BMD) were assessed before and 12 months after treatment.There were no significant differences in all baseline parameters between two groups (P > 0.05).After 1 month of treatment,the VAS scores of study group was lower than that of the control group (2.1 ± 3.0 vs.4.2 ± 3.1,P < 0.05),however,both groups had similar improvements in VAS scores in 6 and 12 months after the treatment (P >0.05).Compared to those before treatment,physical component summary and mental component summary of SF-12 scores after 1 year of treatment were improved significantly in both groups (P < 0.05).Also,BMD was significantly improved after 1 year of treatment in both groups (P < 0.05).The incidence of side effect in study group was lower than that in control group (16% vs.20%,P <0.05).The results indicate that salmon calcitonin combined with zoledronic acid is an effective,safe,reliable and well tolerated therapy for senile primary osteoporosis.The long-term outcomes remain to be determined.%对2012年1月至2013年4月在我院接受诊治的120例老年原发性骨质疏松症患者(男41例,女性79例),除常规补充钙剂外,60例采用鲑鱼降钙素联合唑来膦酸注射液治疗(观察组),60例采用阿仑膦酸钠治疗(对照组).药物剂量为肌肉注射鲑鱼降钙素50 U/次、1

  16. Effect of Qianggu Capsule combined with salmon calcitonin injection treatment on bone min-eral density and bone metabol ism in patients with senile osteoporotic compression fractures%强骨胶囊联合鲑鱼降钙素针剂治疗对老年骨质疏松性压缩骨折患者骨密度及骨代谢的影响

    Institute of Scientific and Technical Information of China (English)

    黎立; 司裕

    2016-01-01

    目的::分析强骨胶囊联合鲑鱼降钙素针剂治疗对老年骨质疏松性压缩骨折患者骨密度及骨代谢的影响.方法:92例老年骨质疏松性压缩骨折患者按照随机数表法分为观察组及对照组,各46例,对照组接受单独强骨胶囊治疗,观察组接受强骨胶囊联合鲑鱼降钙素针剂治疗,对比两组骨密度、骨代谢指标及 CT 相关参数差异.结果:观察组治疗3个疗程及6个疗程后骨密度(BMD)值高于对照组(P <0.05);观察组治疗后血清骨钙素(BGP)、甲状旁腺激素(PTH)值高于对照组,Ⅰ型胶原羧基端前肽(CICP)、Ⅰ型胶原羧基端交联肽(CTX-Ⅰ)值低于对照组,尿液中脱氧胶原吡啶交联(D-Pyr)值低于对照组(P <0.05);观察组治疗后松质骨体积(CV)、CV/MV 值高于对照组,髓腔体积(MV)值低于对照组(P <0.05).结论:强骨胶囊联合鲑鱼降钙素针剂可以抑制老年骨质疏松性压缩骨折患者病情进展,优化骨代谢过程并促进成骨过程,具有积极的临床意义.%Objective:To analyze the effect of Qianggu Capsule combined with salmon calcitonin injection treatment on bone mineral density (BMD)and bone metabolism in patients with senile osteoporotic compression fractures.Methods:A total of 92 cases of patients with senile osteoporotic compression fractures were divided into observation group and control group (n=46)according to random number table;control group received Qianggu Capsule treatment alone,observation group received Qianggu Capsule combined with salmon calcitonin injection treatment,and the differences in bone mineral density,bone metab-olism indexes and CT-related parameters were compared between two groups.Results:BMD values of observation group after 3 courses and 6 courses of treatment were significantly higher than those of control group (P<0.05 );serum bone gla protein (BGP)and parathyroid hormone (PTH)values of observation group after treatment were significantly

  17. 鲑鱼降钙素和唑来膦酸治疗绝经后骨质疏松症的成本-效果分析%Cost-effectiveness Analysis of Salmon Calcitonin and Zoledronic Acid in Treating Postmenopausal Osteoporosis

    Institute of Scientific and Technical Information of China (English)

    白瑶; 周学琴; 刘玉琴

    2015-01-01

    Objective To study the cost-effectiveness of calcitonin salmon and zoledronic acid in treating postmenopausal osteoporo-sis.Methods 126casesofpostmenopausalosteoporosiswerecollectedandrandomlydividedintotwogroups:groupAandgroupB.Data was evaluated using the cost-effectiveness analysis of pharmacoeconomics.Results The costs of group A and group B were 2 279.42 and 3 316.79 yuan respectively.The total effective rates of group A and group B were 57.14%and 79.37%respectively.Group B was higher than those in group A,and the difference was statistically significant in two groups (P<0.05).The cost-effectiveness ratios (C/E) of group A and group B were 39.89 and 41.78 respectively.Conclusion Group B has better compliance and is more reasonable as compared with group A.%目的:比较鲑鱼降钙素和唑来膦酸治疗绝经后骨质疏松症( PMOP)的成本与效果。方法将126例PMOP患者分为A组和B组,运用药物经济学原理进行成本-效果分析。结果 A组和B组的治疗成本分别为2279.43元和3316.79元;总有效率分别为57.14%和79.37%,B组明显高于A组,有统计学差异( P<0.05);经济学方面A组和B组的成本-效果比分别是39.89和41.79。结论应用唑来膦酸治疗绝经后骨质疏松症比鲑鱼降钙素更为合理。

  18. Preparation of salmon calcitonin dry powder in-halation and influential factors of its content%鲑鱼降钙素肺部干粉吸入剂的制备及含量影响因素的考察

    Institute of Scientific and Technical Information of China (English)

    孟康康; 任亚超; 唐星; 金凤珠

    2008-01-01

    目的 喷雾干燥法制备鲑鱼降钙素(salmon calcitonin,sCT)肺部干粉吸入剂;考察溶液pH值、喷干温度和处方中泊洛沙姆(F68)的用量对鲑鱼降钙素含量的影响.方法 分别制备不同pH值和不同F68用量的鲑鱼降钙素溶液,在不同温度下喷雾干燥制备鲑鱼降钙素干粉吸入剂粉末,用高效液相色谱仪对所制备的粉末进行含量测定.采用TSI装置测定粉末沉积率,用LS320激光粒度测定仪测定粒径大小,用扫描电子显微镜观察粉末的表面形态.结果 制备的鲑鱼降钙素吸入粉末的平均粒径为2.1μm,沉积率在45.42%左右.在pH小于3.3的冰醋酸溶液中,F68的用量超过固型物总量的1%时,喷干温度低于120℃时,鲑鱼降钙素喷雾干燥后的含量均在80%以上.结论 在较低的pH环境中,选用适量的蛋白保护剂F68,采用较低的喷干温度,均可有效的降低喷干过程中鲑鱼降钙素的变性几率.

  19. Role of Calcitonin Original Level Testing in Identifying Strains of Bloodstream Infections of Patients in ICU%降钙素原水平检测对鉴别重症监护病房血流感染患者菌种的作用

    Institute of Scientific and Technical Information of China (English)

    龚剑锋; 向镜芬; 杨祥; 孟启勇; 雷伟健

    2015-01-01

    目的:探讨PCT水平对鉴别重症监护病房血流感染患者菌种的价值。方法:选择2011年3月-2014年1月本院ICU患者131例作为研究对象,按照其菌种将其分为G-组、G+组及真菌组,比较各组PCT水平差异,并根据其ROC曲线判断血清PCT的诊断性能。结果:三组血清PCT中位数水平差异具有统计学意义(P<0.05);血清PCT水平对G-菌与G+菌及真菌所致的血流感染鉴别诊断性能较高。结论:血清PCT水平对于鉴别G-菌与G+菌或真菌引起的血流感染有一定的临床鉴别价值,但是对于G+菌与真菌引起的感染鉴别意义尚不明确。%Objective:To investigate the value of calcitonin original level in identifying bacterial bloodstream infections of patients in intensive care unit. Method:131 patients in ICU of our hospital from March 2011 to January 2014 were selected as the objects.They were divided into group G-,group G+and group fungi according to different strains.Differences in PCT levels were compared among the three groups and diagnostic performance of serum PCT was determined according to its ROC curve. Result:Differences in median serum PCT levels of the three groups were statistically significant.Serum PCT level has a higher diagnostic capacity in differentiating bloodstream infections caused by G-bacteria and G+bacteria or fungi.Conclusion:Serum PCT level plays a certain role in differentiating bloodstream infections caused by G-bacteria and G+bacteria or fungi,but it plays an uncertain role in differentiating infections caused by G+bacteria and fungi.

  20. 鲑鱼降钙素对前交叉韧带切断模型兔膝关节软骨损伤的保护作用%Effect of salmon calcitonin on knee joint cartilage lesions in anterior cruciate ligament transection rabbit models

    Institute of Scientific and Technical Information of China (English)

    云文科; 葛茂林; 王剑; 曹磊光; 白杰; 宝音; 任喜存

    2013-01-01

    目的 研究鲑鱼降钙素(salmon calcitonin,sCT)对前交叉韧带切断(anterior cruciate ligament transection,ACLT)模型兔膝关节软骨损伤的影响.方法 将48只健康3月龄雄性日本大耳白兔随机分为3组,每组16只.选择其中两组造模,术后分别给予sCT和生理盐水(normal saline,NS),即ACLT+sCT组和ACLT+NS组;另外一组作为对照组,不予任何处理.8周后处死动物,取关节软骨进行HE染色观察并进行Mankin评分,免疫组化方法检测软骨中MMP-13表达情况;采用骨组织形态计量学比较各组软骨下骨小梁结构变化.结果 软骨HE染色观察、Mankin评分及MMP-13组化评价结果表明,ACLT+sCT组软骨损伤程度轻于ACLT+NS组,但较对照组严重,各组间比较差异有统计学意义(P<0.05).软骨下骨小梁结构定量分析表明,ACLT+sCT组软骨下骨小梁厚度明显高于ACLT+NS组[(263.56±24.30)vs(182.63±182.63)]μm,但低于对照组(361.49±23.36)μm,各组间比较差异具有统计学意义(P<0.05).结论 sCT能够降低ACLT切断所造成的兔膝关节软骨组织损伤程度,同时可部分维持软骨下骨小梁结构,对骨性关节炎软骨有一定保护作用.%Objective To investigate the effects of salmon calcitonin on knee joint cartilage lesions in anterior cruciate ligament transection (ACLT) rat models. Methods Forty - eight three - month - old male rabbits were randomly divided into three groups( n = 16) . Two groups of rabbits underwent anterior cruciate ligament transection( ACLT) surgery, then were subcutaneously injected salmon calcitoin(sCT) and normal saline separately. The other rabbit were untreated as control. After eight weeks, all the rabbits were killed. The sections of cartilage were stained with hematoxylin - eosin ( HE) , and analyzed by Mankin score system. Expression levels of MMP -13 were detected by immunohistochemistry staining. Subchondral bone of proximal tibia was measured by bone histomorphometic method. Results Based

  1. Study of the efficacy of salmon calcitonin combined with alendronate sodium on senile osteoporosis and the regulation mechanism%鲑鱼降钙素联合阿仑膦酸钠治疗老年性骨质疏松的部分机制研究

    Institute of Scientific and Technical Information of China (English)

    方钧; 郑季南; 洪庆南; 陈敏葵

    2015-01-01

    目的:观察鲑鱼降钙素联合阿仑膦酸钠对老年骨质疏松的疗效以及探讨其影响骨代谢的调控机制。方法将本院收治的60例伴有疼痛症状的老年骨质疏松患者,计算机随机分为2组,对照组27例,治疗组33例,对照组口服阿仑膦酸钠70 mg/次/周,治疗组在对照组治疗基础上注射鲑鱼降钙素,50 IU/次,每天,连续7d,第8 d开始以同等剂量隔天注射,第14 d开始同等剂量2次/周,28 d为一个疗程,共6个疗程,检测治疗前后患者疼痛症状、骨密度、血清1,25-(OH)2D3和PTH水平的变化情况。结果①两组治疗后腰背痛量化结果均有一定程度的改善;与对照组比较,治疗组VAS等级综合评分显著下降,差异有统计学意义( P<0.05),对照组腰背痛VAS等级综合评分均>5,而治疗组评分均<4;②两组治疗后第1-4腰椎( L1-L4)和股骨颈、总髋部的骨密度与治疗前相比均具统计学差异(P<0.05),其中治疗组治疗后骨密度远高于对照组(P<0.05);对照组与治疗组在治疗后的T值均显著高于治疗前(P<0.05),且治疗组显著高于对照组(P<0.05);③治疗后对照组患者血清1,25-(OH)2D3水平明显低于治疗组(P<0.05),对照组血清PTH含量明显高于治疗组(P<0.05)。结论骨质疏松发生发展过程中伴有腰背疼痛,骨密度降低,鲑鱼降钙素联合阿仑膦酸钠可能通过增加1,25-(OH)2D3,抑制PTH的合成来改善骨质疏松症状。%Objective To observe the efficacy of salmon calcitonin combined with alendronate sodium on the treatment of senile osteoporosis and to explore its mechanism of regulation of bone metabolism.Methods Sixty elderly patients with osteoporosis were divided into two groups, 27 cases in the control group and 33 cases in the treatment group.The patients in control group received 70mg

  2. 糖尿病大鼠心肌降钙素基因相关肽下调与心肌缺血/再灌注损伤加剧相关性研究%Study on the association of down-regulation of calcitonin gene-related peptide in myocardium with exaggerated myocardial injury after ischemia/reperfusion in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    李兔平; 刘超杰; 郭政

    2015-01-01

    目的 探讨糖尿病大鼠心肌降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的变化与糖尿病心肌易损性增加的相关性. 方法 180 g~200 g雄性Sprague-Dawley(SD)大鼠40只,采用随机数字表法分为两组:正常组(C组)和糖尿病组(DM组),每组20只.DM组采用高糖高脂饲料喂养,C组采用基础饲料喂养.在高糖高脂饲料喂养的第4周,采用小剂量(30 mg/kg)链脲佐菌素(streptozocin,STZ)腹腔注射建立糖尿病DM模型.注射STZ 10周后将DM组和C组采用随机数字表法分为糖尿病缺血/再灌注(ischemia/reperfusion,I/R)组(DM+I/R组)、糖尿病假手术组(DM +Sham组)、正常I/R组(C+I/R组)、正常假手术组(C+Sham组),每组10只.采用结扎冠状动脉左前降支的方法制备心肌I/R模型,采用免疫荧光技术和酶联免疫吸附法(enzyme-linked immuno sorbent assay,ELISA)对CGRP的表达进行定量分析,采用伊文蓝(evans blue,EB)与氯化三苯基四氮唑(triphenyltetrazolium chloride,TTC)染色的方法测量心肌缺血区及梗死区面积. 结果 心肌组织内CGRP免疫反应阳性神经纤维多见于心外膜和心肌层,尤其是血管周围及血管内皮.DM+Sham组心肌CGRP含量[(2 271±339)ng/g]显著低于C+Sham组[(4 369±310) ng/g](P<0.05).经过I/R后,虽然糖尿病大鼠与非糖尿病大鼠心肌组织中CGRP含量均比假手术组显著上调(P<0.05),但DM+I/R组心肌CGRP量[(3 138±423) ng/g]显著低于C+I/R组[(6 192±406) ng/g] (P<0.05).DM+I/R组心肌梗死面积(62.79%)显著大于C+I/R组(43.35%)(P<0.01). 结论 糖尿病导致心肌组织内感觉神经肽CGRP显著减少,该变化可能与糖尿病大鼠心脏I/R损伤加剧有关,相关的机制需进一步研究.%Objective The aim of the study was to investigate the association of change of calcitonin gene-related peptide (CGRP) in myocardium with increase of myocardial vulnerability in diabetic rats.Methods Forty male Sprague-Dawley(SD) rats,weighing 180 g-200

  3. 实验性结肠炎对脊髓传入神经元中降钙素基因相关肽和香草酸受体1表达的调节%Effects of experimental colitis on the expressions of calcitonin gene-related peptide and vanilloid receptor 1 in rat spinal cord sensory neurons

    Institute of Scientific and Technical Information of China (English)

    杨霞; 韩俊庆; 刘然

    2008-01-01

    本文旨在探讨肠道局部炎症对脊髓肠道感觉传入神经通路的近期及远期效应,应用三硝基苯磺酸(trinitrobenzenesulfonic acid,TNBS)建立大鼠结肠炎动物模型,用DiI(3)逆行神经标记法识别支配肠道炎症部位的脊髓背根神经节(dorsalrootganglia,DRG)神经元,通过肉眼观察、平均组织损伤评分及髓过氧化物酶活性测定等方法评价肠道组织的炎症反应状态,用免疫组织化学法测定香草酸受体l(vanilloid receptor 1,VRl)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在支配结肠炎症部位的DRG神经元中的表达,比较炎症不同阶段(给予TNBS后7、21、42 d)CGRP和VRI阳性神经元的数目.结果显示,炎症急性期(即给予TNBS后7 d)结肠黏膜肉眼可见明显损伤,同时相应DRG中表达CGRP及VRl的神经元增加近2倍[(95.38±9.45)%VS(42.86±5.02)%,(89.23±8.21)%VS(32.54±4.58)%].给予TNBS后21、42 d,肠道炎症反应已完全消退,但表达CGRP及VRl的DRG神经元数目仍明显高于对照组[(86.25±8.21)%,(68.28±7.12)%VS(42.86±5.02)%;(67.22±6.52)%,(56.25±4.86)%VS(32.54±4.58)%].结果提示,肠道局部炎症可以上调支配肠道的脊髓传入神经元中CGRP和VRl的表达,这种异常表达可以持续至肠道炎症反应消退后的一定时间.%To study the acute and long-term effects of local gut infammation on the sensitivity of the spinal sensory neurons,the expressions of vanilloid receptor 1(VR1)and calcitonin gene-related peptide(CGRP)in the colon-innervated primary sensory neurons in dorsal root ganglia(DRG)were examined in rats with trinitrobenzenesulfonic acid(TNBS)-induced experimental colitis.The neurons projecting to the distal colon were identified by DiI(3)retrograde labelling.Macroscopic examination,mean damage score and myeloperoxidase(MPO)activity were determined to assess the inflammatory status of the colon tissue.The number of CGRP and VR1 immunoreactive neurons at different stages of

  4. 普瑞巴林对原发性三叉神经痛患者血浆 P物质和降钙素基因相关肽的影响%Influence of Pregabalin on plasma substance P and calcitonin gene-related peptide in patients with trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    熊勋波; 杨涛; 邓刚; 成祥林; 向明清; 刘焰

    2014-01-01

    目的::观察普瑞巴林( PGB )和卡马西平( CBZ )对原发性三叉神经痛( PTN )患者血浆 P 物质( SP )和降钙素基因相关肽( CGRP)以及疼痛视觉模拟评分( VAS)的影响,评估PGB治疗PTN的疗效和安全性。方法:130例PTN患者随机分为观察组64例使用PGB治疗,对照组66例使用CBZ治疗。分别从低剂量开始给药,观察患者的疗效及不良反应至第4周末,两组患者在治疗前和结束时以放免法测定血浆SP和CGRP含量,并进行VAS评分。结果:观察组患者的总有效率89.1%,对照组72.1%,两组患者差异有统计学意义(P<0.05);治疗后两组患者的血浆SP和CGRP均下降,观察组患者较对照组尤为明显(P<0.05)。观察组不良反应发生率31.3%明显低于对照组59.1%。结论:PGB治疗PTN疗效和安全性均高于CBZ。%Objective:To observe influence of Pregabalin ( PGB) and Carbamazepine ( CBZ) on plasma substance P ( SP) , calcitonin gene-related peptide ( CGRP) , and pain visual analogue score ( VAS) for patients with trigeminal neuralgia ( PTN) , and e﹣valuate efficacy and safety of PGB in treatment of PTN. Methods:130 patients with PTN were randomly divided into observation group ( PGB, 64 cases) and control group ( CBZ, 66 cases) . Both groups were administered with low dose at first, and then the therapeutic effect and adverse effect until termination of the fourth week were observed. The plasma SP and CGRP were detected by radioimmuno﹣assay before and after the treatment, while the visual analogue scales ( VAS) were measured. Results:The clinical efficiency of PGB was 89. 1%, that of CBZ was 72. 1%, and there was a significant difference between the two groups (P<0. 05). The treatments re﹣duced plasma SP and CGRP levels in both groups, and the change of PGB group was more obvious than that of CBZ group (P<0. 05). The incidence rate of adverse effect by PGB (31. 3%) was less than that by CBZ (59. 1%) (P<0. 05). Conclusions

  5. Peptídeo relacionado ao gene da calcitonina por iontoforese na viabilidade de retalho cutâneo randômico em ratos Calcitonin gene-related peptide by iontophoresis on the viability of the randon skin flaps in rats

    Directory of Open Access Journals (Sweden)

    Ivaldo Esteves Junior

    2004-12-01

    Full Text Available Objetivo: Investigar o efeito da administração tópica do peptídeo relacionado ao gene da calcitonina (CGRP por iontoforese na viabilidade de retalho cutâneo randômico em ratos. Métodos: Sessenta ratos Wistar EPM-1, adultos e machos foram submetidos a retalho cutâneo randômico. Os animais foram distribuídos aleatoriamente em quatro grupos. Nos animais do grupo 1 (controle, n=15 realizou-se simulação de estímulo elétrico, no grupo 2 (iontoforese placebo, n=15 os animais foram submetidos à corrente contínua, no grupo 3 (controle de absorção, n=15 os animais receberam simulação de estímulo elétrico com CGRP e, por fim os animais do grupo 4 (tratado, n=15 foram tratados com iontoforese de CGRP. Em todos os grupos estes procedimentos foram realizados imediatamente após a técnica operatória e nos dois dias subsequentes. A porcentagem da área de necrose foi avaliada no sétimo dia de pós-operatório. Resultados: A média das porcentagens das áreas de necrose foram: grupo 1- 48%, grupo 2 - 51%, grupo 3 - 46% e, grupo 4 - 28%. A análise estatística, através do teste de Kruskal-Wallis, evidenciou diferença significante (pPurpose: Assess the effect of the local administration of calcitonin gene-related peptide (CGRP by iontophoresis on the viability of random skin flap in rats. Methods: Sixty Wistar-EPM 1 rats were submitted to dorsal skin flap of cranial base 10 x 4 cm with interposition of a plastic barrier between the skin flap and the donnor site. The animals were randomly distributed in four groups (n = 15 in each group and were treated as follows: in group 1 (control, animals were submitted to a simulation of electrical current for 20 minutes; group 2, (iontophoresis placebo animals were submitted to direct current of 4mA amplitude for 20 minutes; group 3 (absorption control receive simulation of electrical current for 20 minutes with CGRP on one of the electrodes; group 4 (iontophoretically treated treated by

  6. 腹膜透析并发感染性腹膜炎患者血清降钙素原检测的临床意义%Peritoneal Dialysis Concurrent Infectious Peritonitis in Patients with Serum Calcitonin Original Clinical Significance of Detection

    Institute of Scientific and Technical Information of China (English)

    宋新宇

    2016-01-01

    目的:探讨分析腹膜透析并发感染性腹膜炎患者血清降钙素原检测的临床意义。方法选取我院2013年1月至2015年7月期间腹膜透析中心24例接受腹膜透析的患者作为研究分析对象,同时,所选24例患者均接受电化学发光免疫分析法进行检测,依据检测结果将其分为非腹膜炎组(12例)、腹膜炎组(12例),并选取同时期到我院体检健康者12例作为对照组,三组研究对象均接受血清降钙素原检验,比较三组研究对象检测结果。结果非腹膜炎组和腹膜炎组比较血清 PCT 指数,腹膜炎组明显高于非腹膜炎组,组间数据有统计学意义(P0.05);非腹膜炎组和腹膜炎组比较,血清 CRP 指数明显升高(P0.05)。结论腹膜透析并发感染性腹膜炎患者的血清降钙素原检测指数有明显升高趋势,临床中,对腹膜透析并发感染性腹膜炎疾病的判定有一定作用,同时也可用来评价临床治疗状况。%Objective To investigate the clinical significance of serum levels of calcitonin in patients with peritoneal dialysis complicated with infection. Methods 2013 January to July 2015 during peritoneal dialysis center 24 cases accepted peritoneal dialysis patients as the analysis object, at the same time, the selected 24 patients underwent electrochemical luminescence immunoassay was used to detect the. Based on the test results will be classified as non peritonitis group (12 cases), the peritonitis group (12 cases), and select the same period in our hospital for a medical examination of the health and 12 cases as control group, three groups of subjects were treated with serum procalcitonin test, were compared among the three groups of research object detection results. Results The peritonitis group and peritonitis group serum PCT index, peritonitis group was significantly higher than that in non peritonitis group was statistically significant between two groups of data

  7. 不同给药方式下降钙素基因相关肽在蛛网膜下腔出血大鼠的组织分布%Tissue distribution of calcitonin gene-related peptide administered via different routes in rats with subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    吴庆建; 孙树印; 宋大庆; 张颜波; 闫承军; 孙保亮

    2015-01-01

    Objective To investigate the tissue distribution of calcitonin gene-related peptide (CGRP) by nasal versus intravenous administrations in rats with subarachnoid hemorrhage (SAH).Methods The SAH rat model was established by injecting fresh autologous arterial blood into cisterna magna twice.Sixty-four rats were divided into 4 groups by random digit table:(1) group A (n=16):the normal rats were treated with 125I marked CGRP (125I-CGRP) by nasal administration;(2) group B (n=16):the SAH model rats were treated with 125I-CGRP by nasal administration;(3) group C (n=16):the normal rats were treated with 125I-CGRP via femoral vein;(4) group D (n=16):the SAH model rats were treated with 125I-CGRP via femoral vein.The tissue distribution of CGRP in rats of each group at 30 min after the treatment was compared by radioisotope tracing.Results The CGRP concentrations of brain regions,spinal cord,and cerebrospinal fluid (CSF) in normal rats and SAH model rats by nasal administration of 125I-CGRP were significantly higher than those by intravenous administration;whereas the CGRP concentrations of blood,thyroid,deep cervical lymph nodes,liver and lung tissues in normal rats and SAH model rats by nasal administration of 125I-CGRP were significantly lower than those by intravenous administration (all P<0.05).After nasal administration,the CGRP concentration in the olfactory bulb was the highest,followed by those in CSF and spinal cord.Conclusion Tissue distribution of CGRP differs between nasal administration and intravenous administration.Nasal administration of CGRP shows significant advantages in the medical treatment for disorders of the central nervous system.%目的 探讨经鼻给药、经静脉给药降钙素基因相关肽(CGRP)在蛛网膜下腔出血(SAH)大鼠的组织分布.方法 采用枕大池两次注入新鲜自体动脉血的方法建立SAH大鼠模型,64只大鼠按随机数字表法分为4组:(1)A组(n=16):经鼻给予125I标记的CGRP(125I

  8. Effects of Duliang capsule on the expression of calcitonin gene-related peptide and cholecystokinin in the midbrain of a rat migraine model%都梁软胶囊对偏头痛模型大鼠中脑CGRP及CCK 表达的影响

    Institute of Scientific and Technical Information of China (English)

    韩喜梅; 姚刚; 满玉红; 于挺敏

    2016-01-01

    目的:研究都梁软胶囊对偏头痛模型大鼠中脑降钙素基因相关肽(CGRP)和缩胆囊肽(CCK)基因转录水平的影响,探讨其预防治疗偏头痛的作用机制。方法健康Wistar大鼠随机分4组,A为对照组,B为偏头痛组,C为都梁软胶囊对照组,D为都梁软胶囊治疗组。C、D组给予都梁软胶囊0.5g·kg -1·d-1灌胃,A、B组大鼠灌胃给予等量容积的 Tween‐80。灌胃7 d后,将B、D两组大鼠造硝酸甘油型偏头痛模型,造模2 h ,保存中脑标本。实时荧光定量PCR检测CGRP和CCK的转录水平。结果 D组大鼠中脑CGRP转录水平明显低于B组(0.64±0.35和1.61±0.51,P<0.05)。C组大鼠中脑CCK 转录水平明显低于A组(0.32±0.31和1.21±0.38,P<0.05)。结论都梁软胶囊可以干预中脑CGRP和CCK的表达,从而影响内源性痛觉调制系统的功能。%Objective To study the effects of Duliang capsule on the expression of calcitonin gene‐related peptide(CGRP) and cholecystokinin(CCK) in the midbrain of a rat migraine model ,and explored treatment effects and mechanisms of Duliang cap‐sule on rats with migraine .Methods A total of 24 rats were randomly divided into four groups :normal control groups(A) ,migraine model groups(B) ,Duliang capsule control groups(C) and Duliang capsule treatment groups(D) .C and D were intragastrically per‐fused with Duliang capsule(0 .5 g · kg -1 · d-1 ) .After 7 days ,nitroglycerin was subcutaneously injected into the buttocks of the B and D to induce migraine .Two hours after nitroglycerin injection ,the midbrain were isolated CGRP and CCK expression in midbrain were determined using SYBR Green I real‐time quantitative PCR .Results CGRP mRNA expression was significantly lower in mid‐brains of rats in the Duliang capsule treatment groups compared with migraine model groups(P<0 .05) .CCK mRNA expression was significantly lower in midbrains of rats in the

  9. Effects of xenotransplantation of microencapsulated sciatic nerve tissue cells on the expression of calcitonin gene-related peptide after spinal cord injury in rats%异种细胞移植对大鼠损伤脊髓降钙素基因相关肽表达的影响

    Institute of Scientific and Technical Information of China (English)

    段平国; 孙贵才; 刘德明

    2011-01-01

    Objective: To observe the effects of xenotransplantation of the microencapsulated sciatic nerve tissue/cella on the expression of calcitonin gene-related peptide (CGRP) after spinal cord injury (SCI) in rats.Methods: Bilateral sciatic nerves of rabbits were preconditioned for 1 week were dissected under sterile conditions and made into nerve tissue/cells suspension which was mixed with 1.5% sodium alginate solution.The mixture was then extruded using a droplet generation device into 20 mmol/L barium chloride solution to form barium-alginate capsules.Microencapsulated nerve tissue/cells suspension was implanted into the injured sites of the spinal cord in rats.By immunohistochernstry, the expressions of CGRP were observed.Results: The number of CGRP-positive cells in the right ventral horn of spinal cord of rats reduced remarkably in each group after SCI, and it gradually recovered in varying degrees 1 week later.The difference of the number of CGRP-positive cells between the microcapsule group and the cell group was not remarkable, but both of them existed in the distinction when compared with the injury group (P <0.05).At 2, 4 weeks and 8 weeks after SCI, compared to the cell group and injury group,the number of CGRP-positive cells in the microcapsule group increased obviotrsly.Conclusion: The xenotransplantation of the microencapsulated sciatic nerve tissue/cells promotes the expression of CGRP after SCI in rats, benefiting the regeneration of neuron.%目的:观察微囊化异种坐骨神经组织细胞移植对脊髓损伤大鼠降钙素基因相关肽(CGRP)表达的影响.方法:取家兔预变性处理1周的坐骨神经制成组织细胞悬液,与1.5%海藻酸钠溶液混合并喷入20mmol/L氯化钡溶液中制成微囊化的组织细胞悬液.将其植入SD大鼠脊髓损伤处,通过免疫组织化学显色观察CGRP的表达情况.结果:SCI后各组大鼠右侧脊髓前角CGRP阳性细胞数减少,1周后均不同程度地逐渐恢复.SCI后1周,细

  10. Effect of Drug Pair of Coptis Chinensis and Evodia Rutatecarpa on Blood Pressure,Plasma Endothelin and Calcitonin Gene - related Peptide in Spontaneous Hypertension Rats%药对黄连、吴茱萸对高血压大鼠血压和血浆ET、CGRP的影响

    Institute of Scientific and Technical Information of China (English)

    卜宪峥; 吴华芹; 胡元会; 褚瑜光; 宋庆桥; 王师菡

    2011-01-01

    Objective To investigate the effects of drug pair of coptis chinensis and evodia rutatecarpa on blood pressure.the content of plasma endothelin(ET) .and calcitonin gene - related peptide (CGRP) in spontaneous hypertension rats(SHR). Methods Twenty - four SHR were randomly divided into model group(n = 8) .nifedipine group(n = 8) given nifedipine .and Lianyu decoction group(w=8) given Lianyu oral liquid by continuously gavages. Eight normal Wistar - Kyoto rats(WKY) were as control (WKY group). WKY group and Model group were given normal saline. After treatment for 4 weeks* blood pressure,the content of plasma ET and CGRP were measured. Results Compared with model group, the blood pressure in Lian - Yu decoction group was significantly lower (P<0. 01). The content of ET was decreased (P<0. 05) .while the content of plasma CGRP was greatly increased (P<0. 01) in Lianyu decoction group. Conclusion Drug pair of coptis chinensis and evodia rutatecarpa could significantly reduce blood pressure in SHR, which might be related to reduce the content of plasma ET and increase the content of plasma CGRP.%目的 观察药对黄连、吴茱萸对自发性高血压大鼠(SHR)血压和血管活性物质内皮素(ET)、降钙素基因相关肽(CGRP)含量的影响.方法将24只SHR随机分为模型组(Model组)、硝苯地平组(Nif组)、连萸药对组(LY组),每组8只,以正常WKY大鼠为对照组(WKY组),8只,共4组.WKY组和Model组予以生理盐水,Nif组予以硝苯地平溶液,中药组予以相应配伍剂量的浓煎剂,连续灌胃4周,测量大鼠灌胃前和灌胃4周末大鼠尾动脉的收缩压.第4周末同时测定大鼠血浆中ET、CGRP的含量.结果 与Model组比较,中药组大鼠4周后血压水平明显降低(P<0.05),血浆ET含量降低(P<0.05),CGRP的含量明显升高(P<0.05),但与Nif组相比无统计学意义.结论 药对黄连、吴茱萸对SHR有明显的降压作用,其机制可能与降低血浆中ET的含量,增加CGRP的含量有关.

  11. 大鼠肾脏缺血再灌注损伤中垂体中叶素及降钙素受体样受体的表达%Expression changes of intermedin and calcitonin receptor-like receptor in the kidney of rats after renal ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    于桂花; 李荣山; 乔唏; 周芸; 寇敏; 王晨; 白波; 邵珊

    2009-01-01

    Objective To investigate the expressions of intermedin /adrenomeduliin 2 (IMD/AM2) and its receptor calcitonin receptor-like receptor (CRLR) in the kidney of rats after renal ischemia reperfusion injury(IRI). Methods Male Wistar rats were divided randomly into two groups: sham group and operation group. Renal IRI model was induced by clamping both renal arteries. Blood and kidney were harversted at 0 h, 6 h, 12 h, 24 h, 48 h, 72 h after reperfusion, respectively. Renal histological changes were semi-quantitated. Expressions of IMD and CRLR in the kidney were detected by Western blot, and the content of IMD in serum was measured by radioimmunity at 12 h, 48 h, 72 h after repeffusion. Results Kidneys of renal IRI model rats displayed significant pathologic changes, and the changes were much severer at 48 h after reperfusion. The expressions of IMD and CRLR in kidney were significantly up-regnlated at 12 h, 48 h, 72 h after renal IRI (P<0.01). The level of IMD in serum increased at 12 h, 48 h, 72 h after renal IRI (P<0.05). Conclusion The expressions of IMD and its receptor are up-regulated in the kidney after renal IRI, which may participate in the pathophysiological changes induced by renal IRI.%目的 观察垂体中叶素(IMD)及其受体降钙素受体样受体(CRLR)在大鼠肾脏缺血再灌注损伤中的表达变化.方法 将健康雄性Wistar大鼠随机分为假手术组和手术组,夹闭大鼠双侧.肾动脉制作肾脏缺血再灌注损伤(IRI)模型,于缺血再灌注后0、6、12、24、48、72 h 6个时间点各取6只大鼠,留取血清及肾组织标本,对肾脏病理损伤评分并行半定是量分析;Western印迹法半定量分析肾组织IMD及其受体CRLR的表达变化;放射免疫法检测血浆中IMD的表达变化.结果 手术组大鼠发生了急性肾小管坏死(ATN),以缺血再灌注48 h时病理损伤最重.与假手术组比较.IMD及CRLR在缺血再灌注12、24、48、72 h表达显著增高(均P<0.01);

  12. Effect of gamma-aminobutyric acid treatment on plasma substance P and calcitonin gene-related peptide levels in children with asthma%γ-氨基丁酸治疗对哮喘患儿血浆P物质和降钙素基因相关肽含量的影响

    Institute of Scientific and Technical Information of China (English)

    徐传伟; 郭山春; 郑振文; 王庆元

    2013-01-01

    目的 探讨γ-氨基丁酸(GABA)治疗前后哮喘患儿血浆P物质(SP)和降钙素基因相关肽(CGRP)含量的变化.方法 75例哮喘患儿随机分为GABA治疗组(36例)和对照组(39例),两组患儿均给予哮喘常规治疗.治疗组在常规治疗的基础上给予GABA口服(每日25 ~ 30 mg/kg).采用酶联免疫吸附法(ELISA)测定患儿治疗前、缓解后血浆SP、CGRP的含量.结果 两组患儿治疗前血浆SP、CGRP含量差异无统计学意义(P>0.05);哮喘缓解后治疗组血浆SP、CGRP含量分别为57±15 pg/mL、23±10 pg/mL,显著低于对照组(分别为127±12 pg/mL、42 ±8 pg/mL),差异有统计学意义(P<0.01).两组哮喘缓解后血浆SP、CGRP含量均较治疗前明显下降,差异有统计学意义(P<0.01).哮喘患儿血浆SP与CGRP含量呈显著正相关(r=0.792,P<0.01).结论 GABA可抑制小儿哮喘急性发作期血浆SP、CGRP的释放.%Objective To study the changes in plasma substance P (SP) and calcitonin gene-related peptide (CGRP) levels in children with acute asthma before and after gamma-aminobutyricacid (GABA) treatment. Methods Seventy-five children with asthma were randomly assigned to GABA treatment ( n = 36 ) and control groups ( n = 39 ) . Both groups were given conventional treatment for asthma. Besides the conventional treatment, the treatment group was administered with oral GABA (25 - 30 mg/kg·d). Plasma content of SP and CGRP was measured using ELISA before treatment and after remission. Results There were no significant differences in plasma content of SP and CGRP between the GABA treatment and control groups (P > 0.05) before treatment. Plasma content of SP and CGRP in the GABA treatment group was significantly lower than the control group (SP: 57 ± 15 pg/mL vs 127 ± 12 pg/mL; CGRP: 23 ± 10 pg/mL vs 42 ± 8 pg/mL) after remission (P<0. 01). Plasma content of SP and CGRP after remission was significantly lower than before treatment (P <0.01) in both groups. There was a

  13. Calcitonin Gene-Related Peptide and Migraine: Implications for Therapy

    NARCIS (Netherlands)

    U. Arulmani (Udayasankar)

    2004-01-01

    textabstractIt is clearly evident from the literature that headache has troubled mankind from the dawn of civilization (Rapoport & Edmeads, 2000). A variety of methods have been used throughout the ages in an attempt to alleviate or cure this pain; these may have been the most appropriate at that

  14. Pro-calcitonin and inflammation in chronic hemodialysis

    Directory of Open Access Journals (Sweden)

    Hernán Trimarchi

    2013-10-01

    Full Text Available Procalcitonin (PCT has emerged as a marker of infection, a frequent complication in hemodialysis (HD. We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients.In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. Variables: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP, albumin, malnutrition inflammatory score (MIS, hematocrit, leukocyte count, and body mass index (BMI. Subsequently, control (G1, n = 36, 43% vs. non-infected patients (G2, n = 48, 57% groups were compared. In control subjects (G1, age: 54.3 ± 13.7 years, range (r: 30-81; males: 19 (53%; median PCT 0.034 ng/ml (r: 0.02-0.08; median CRP 0.80 mg/dl (r: 0.36-3.9; p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%, time on HD: 27.0 ± 24.4; diabetics: 19 (32%; median PCT: 0.26 ng/ml (r: 0.09-0.82; CRP: 1.1 mg/dl (r: 0.5-6.2; p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: ρ = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

  15. Increased circulating calcitonin gene-related peptide (CGRP) in cirrhosis

    DEFF Research Database (Denmark)

    Bendtsen, Flemming; Schifter, S; Henriksen, Jens Henrik

    1991-01-01

    with minor disorders (59 vs. 46 pmol/l, p less than 0.01), as well as with 232 healthy persons (37 pmol/l, p less than 0.0001). Moreover, circulating CGRP increased significantly with the severity of cirrhosis (Child-Turcotte group A, 56; group B, 59; group C, 71 pmol/l; p less than 0.025). No significant...

  16. Mapping the calcitonin receptor in human brain stem

    DEFF Research Database (Denmark)

    Bower, Rebekah L; Eftekhari, Sajedeh; Waldvogel, Henry J

    2016-01-01

    understanding of these hormone systems by mapping CTR expression in the human brain stem, specifically the medulla oblongata. Widespread CTR-like immunoreactivity was observed throughout the medulla. Dense CTR staining was noted in several discrete nuclei, including the nucleus of the solitary tract...

  17. Effect of calcitonin combined with alfacalcidol on clinical outcome, lumbar vertebrae bone mineral density and safety in patients undergoing internal fixation of humeral shaft fracture%依降钙素联合阿法骨化醇对行内固定术肱骨干骨折患者临床效果、腰椎骨密度及安全性的影响

    Institute of Scientific and Technical Information of China (English)

    黄志华; 凌飞

    2016-01-01

    目的:探究依降钙素联合阿法骨化醇对行内固定手术的肱骨干骨折患者临床效果、腰椎骨密度及安全性的影响。方法选取2010年6月~2016年6月于寻乌县人民医院选择内固定手术治疗的肱骨干骨折患者80例,随机分为对照组和观察组,各40例。对照组术后给予碳酸钙D3片和功能锻炼治疗,观察组在对照组基础上行依降钙素和阿法骨化醇联合治疗,分析并对比2组临床效果、腰椎骨密度及安全性情况。结果与治疗前比较,2组治疗2、3 w血清钙水平显著升高( P<0.05);对照组治疗12 w腰椎骨密度显著升高( P<0.05),观察组治疗4、12 w腰椎骨密度显著升高( P<0.05)。与对照组比较,观察组治疗2、3 w血清钙水平较高(P<0.05);治疗4、12 w腰椎骨密度较高(P<0.05)。观察组和对照组治疗后总不良反应率分别为10.00%和15.00%,差异无统计学意义。结论依降钙素和阿法骨化醇联合治疗内固定手术的肱骨干骨折患者效果显著,能够改善患者血清钙水平,促进腰椎骨密度提高,且不良反应较少。%Objective To analyze the effect of calcitonin combined with alfacalcidol on clinical outcome,lumbar vertebrae bone mineral density and safety in patients undergoing internal fixation of humeral shaft fracture.Methods 80 patients with humeral shaft fracture treated with internal fixation in Xunwu county people's hospital from June 2010 to June 2016 were selected,and randomly divided into control group and observation group,40 cases in each groups.The control group was given calcium carbonate D3 tablets and functional exercise therapy,the observation group treated calcitonin combined with alfacalcidol on the basis of control group,analysis and comparison the clinical effects,lumbar spine BMD and safety.Results Compared with before treatment,serum calcium level of two groups increased significantly at treatment 2

  18. 围植入期二硫化碳暴露对小鼠子宫组织降钙素和黄体酮水平的影响%Effect of carbon disulfide exposure during peri-implantation period on levels of calcitonin and progesterone in uterus of mice

    Institute of Scientific and Technical Information of China (English)

    杨柳; 王志萍

    2013-01-01

    目的 观察二硫化碳(CS2)对孕鼠子宫组织降钙素和黄体酮(P4)水平的影响,探讨围植入期暴露CS2致胚胎植入障碍的作用机制.方法 168只健康雌性昆明孕鼠随机分到4种处理的14个观察终点组中,分别在孕3 d(GD3)、GD4、GD5、GD6腹腔注射631.4 mg/kg剂量的CS2(观察终点的染毒组)或橄榄油(观察终点的对照组)1次;在不同的观察终点(GD4、GD5、GD6、GD7、GD9)结束实验.采用酶联免疫吸附试验(ELISA)检测各观察终点孕鼠子宫组织中降钙素及P4水平.结果 胚胎围植入期不同时点暴露于CS2均可导致孕鼠胚胎植入数目减少,GD3、GD4、GD5和GD6染毒组胚胎植入数目分别比对照组减少了42.85%、63.74%、60.45%和47.26%,差异均有统计学意义(P<0.01).GD3、GD4、GD5和GD6染毒组各观察终点孕鼠子宫组织中降钙素表达水平下降,差异均有统计学意义(P<0.05).GD3、GD4和GD5暴露组孕鼠子宫组织P4水平下降,差异均有统计学意义(P<0.05).GD3、GD4、GD5和GD6染毒组胚胎植入数目与子宫组织降钙素和P4表达水平呈正相关(r=0.670和r=0.632,P<0.01);孕鼠子宫组织降钙素表达水平与P4水平呈正相关(r=0.325,P<0.01).结论 围植入期暴露CS2可降低孕鼠子宫组织降钙素和P4表达水平,可能是CS2致胚胎植入障碍的分子机制之一.%Objective To evaluate the effect of carbon disulfide (CS2) exposure during the peri-implantation period on the levels of calcitonin (CT) and progesterone (P4) in the uterus of pregnant mice and to investigate the mechanism of embryo loss induced by CS2 exposure during the peri-implantation period.Methods A total of 168 healthy pregnant Kunming mice were randomly assigned to receive an intraperitoneal injection of CS2 (631.4 mg/kg) or olive oil (control) on gestational day (GD) 3,GD4,GD5,or GD6.The experiment was completed at different end points (GD4,GD5,GD6,GD7,and GD9).The levels of CT and P4 in the uterus were

  19. 神经肽P物质、降钙素基因相关肽在膝骨性关节炎软骨下骨中的表达%Neuropeptides substance P and calcitonin gene related peptide expression in knee osteoarthritis ;subchondral bone

    Institute of Scientific and Technical Information of China (English)

    付昌马; 杨祖华

    2014-01-01

    Objective To study the expression of neuropeptide substance P (SP) and calcitonin gene related peptide (CGRP) in the subchondral bone patients with knee osteoarthritis (OA). Methods A total 40 patients with OA were used as study group, and 10 patients with lower femur fractures were used as control group. Immunohistochemical staining were used to analyze neuropeptides SP and CGRP positive expression in 40 cases OA patients and 10 cases lower femur fractures patients. Results (1) The number of neuropeptide SP positive cells (2.62±0.31 vs. 1.58±0.32, P<0.05) and neuropeptide CGRP positive cells (2.58±0.23 vs. 1.55±0.25, P<0.05) was significantly higher in OA group than control group. (2) Neuropeptide SP average optical density(0.345±0.031 vs. 0.224±0.072, P<0.05) and neuropeptide CGRP average optical density(0.585±0.043 vs. 0.326±0.065, P<0.05) was significantly higher in OA group than control group. (3) Neuropeptide CGRP average optical density (0.585±0.043) was higher than the average optical density of SP (0.345±0.031) (P<0.05) in OA group. Conclusion Significantly higher neuropeptide SP and CGRP levels were found in patients with OA;neuropeptide expression leading to bone metabolic imbalance, adjustment disorder with cycles occur within the joint, and thus play a role in OA group.%目的:研究证明含有神经肽 P 物质(SP)、降钙素基因相关肽(CGRP)共同存在于膝骨性关节炎(OA)中,本研究验证这些肽能神经在膝OA发病中可能起作用。探讨膝OA患者软骨下骨中神经肽SP、 CGRP的表达及临床意义。方法收集2010年4月至2013年9月在合肥市第三人民医院治疗的40例膝OA患者及10例股骨下段骨折患者临床资料。免疫组化染色检测40例膝OA患者(OA组)及10例股骨下段骨折患者(正常对照组)软骨下骨组织神经肽SP、 CGRP的阳性表达。结果(1)40例膝OA患者与10例正常对照组比较,神经肽SP的阳性细胞表达数(2.62

  20. 受体成分蛋白在降钙素基因相关肽和血管紧张素Ⅱ对血管平滑肌细胞血管过氧化物酶1表达调控中的作用%Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin Ⅱ in vascular smooth muscle cell

    Institute of Scientific and Technical Information of China (English)

    刘彦梅; 彭虹艳; 郭锋; 全海燕; 骆镜妃; 秦旭平

    2015-01-01

    血管紧张素Ⅱ (angiotensin Ⅱ,Ang Ⅱ)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在血管的损伤和保护中起重要作用.为了探讨CGRP受体成分蛋白(receptor component protein,RCP)在CGRP和Ang Ⅱ对血管平滑肌细胞(vascularsmooth muscle cell,VSMC)血管过氧化物酶1(vascular peroxidase-1,VPO1)表达调控中的作用及机制,本研究采用体外培养鼠源性Al0血管平滑肌细胞株(A10VSMC),给予CGRP或/和Ang Ⅱ刺激,并用小干扰RNA (siRNA)干扰细胞RCP基因的表达,Western Blot检测RCP以及VPO1蛋白表达水平;RT-PCR检测RCP及VPO1 mRNA的表达水平.结果显示,在静止期野生型A10VSMC,CGRP和Ang Ⅱ能分别上调RCP和VPO1蛋白和mRNA表达(均P<0.05),但CGRP预孵育细胞后,Ang Ⅱ诱导的RCP和VPO1蛋白表达降低(均P<0.05);与野生型组比较,VPO1在所有RCP基因干扰组的表达均显著降低(均P<0.01).同时,在RCP基因干扰条件下,和对照组相比,CGRP处理组VPO1蛋白的表达显著增加,而Ang Ⅱ组没有明显变化;和Ang Ⅱ1组相比,CGRP与Ang Ⅱ联合作用显著增加VPOl蛋白表达,但这种作用能被抗氧化酶Catalase所抑制(P<0.05).以上结果提示,RCP可能参与CGRP或Ang Ⅱ诱导的VPO1蛋白表达;RCP可能在介导CGRP和Ang Ⅱ受体共同调控VPO1表达的信号转导整合中起一定作用.

  1. Relationship between Visceral Hyperalgesia in Developing Rats and Expression of Calcitonin Gene-Related Peptide in Different Regions of Brain%幼鼠内脏痛高敏感性与不同脑区降钙素基因相关肽表达的关系

    Institute of Scientific and Technical Information of China (English)

    陈素清; 吴斌; 林希; 杨燕珍

    2011-01-01

    目的 采用新生期伤害性结直肠刺激(CI)建立幼鼠痛高敏感模型,检测痛觉敏感幼鼠模型下丘脑室旁核、中缝核和前皮质扣带回内降钙素基因相关肽(CGRP)的分布和表达,探讨不同脑区CGRP异常表达参与痛觉高敏感形成的可能机制.方法 8日龄新生SD大鼠分为4组,每组8只.CI+CRD组新生期给予CI,并在6周龄时给予结直肠扩张(CRD)刺激;CI组新生期给予CI,但在6周龄时不予CRD刺激;CRD组新生期不予CI,6周龄时给予CRD刺激;对照组新生期不予CI,6周龄时也未给予CRD刺激.CI+CRD组和CI组乳鼠在出生8~15 d,每天接受1次CI.常规喂养至6周龄,CI+CRD组和CRD组幼鼠进行CRD刺激下内脏痛敏感性评价.采用SABC免疫组织化学法检测4组幼鼠不同脑区内CGRP表达情况.结果 随着CRD的增加,CI+CRD组和CRD组幼鼠腹外斜肌放电波幅逐渐增加.在CRD为2 kPa、4 kPa、6 kPa和8 kPa扩张压刺激下,CI+CRD组腹外斜肌放电幅值显著高于CRD组,差异有统计学意义(F=43.261,P=0.000;F=15.389,P=0.002;F=8.024,P=0.013;F=6.287,P=0.025).而当CRD为10 kPa高扩张压刺激时,CI+CRD组和CRD组腹外斜肌放电幅值差异无统计学意义(F=0.502,P=0.490).新生期CI导致幼鼠下丘脑室旁核、前扣带回皮质、中缝核内CGRP阳性细胞数明显增加的主效应分别为12.23、12.74和11.81,接受CRD刺激后可导致幼鼠CGRP阳性细胞数明显增加的主效应分别为16.81、18.00和17.18.结论 新生期持续CI会造成幼鼠痛阈下降,出现慢性内脏痛高敏感性.幼鼠慢性内脏痛敏感性异常可能与前皮质扣带回、下丘脑室旁核、中缝核内CGRP异常表达相关.CGRP可能作为一种神经递质参与内脏痛觉敏感的改变.%Objective To establish the model of visceral hyperalgesia in developing rats by colorectal irritation ( CI), detect the distribution and expression of calcitonin gene - related peptide(CGRP) in hypothalamus paraventricular nucleus

  2. Distribution and source of calcitonin gene-related peptide immunoreactive nerve terminal in prepuce of penis and frenulum of prepuce of rats%大鼠阴茎包皮及包皮系带内降钙素基因相关肽免疫阳性神经末梢的分布与起源

    Institute of Scientific and Technical Information of China (English)

    吴仲敏; 王东红; 赵礼东; 凌树才; 朱晞

    2006-01-01

    树枝状或念珠状分布,大多成束走行,长短不一,有的呈结节状膨大.②阴茎系带处降钙素基因相关肽免疫阳性神经末梢的分布密度明显大于阴茎包皮处(2.15±0.32,1.02±0.22,t=-2.03,P<0.01).③结合荧光金逆行标记法研究发现,这些神经末梢起源于第6腰髓对应的背根神经节和第1骶髓对应的背根神经节的神经元.荧光金逆标阳性神经元大小不等,胞体呈圆形或卵圆形,未见明显的突起,胞浆内有明亮的金黄色细小颗粒,胞核无标记.细胞大多沿神经束成行排列或散在分布.进一步作降钙素基因相关肽免疫荧光标记后发现降钙素基因相关肽单标阳性神经元大多为中小型细胞,染色较深,反应产物均匀分布于胞浆内,呈明亮的深绿色(FITC标记色).在不同激发光下对照观察同一张阳性切片,发现荧光金/降钙素基因相关肽双标阳性细胞均为中小型,其数量占荧光金逆行标记阳性细胞总数的二分之一.结论:降钙素基因相关肽可能参与大鼠阴茎包皮以及包皮系带感觉信息的传递.大鼠阴茎包皮系带内降钙素基因相关肽免疫阳性神经末梢源自于第6腰髓对应的背根神经节和第1骶髓对应的背根神经节的神经元.%BACKGROUND: Frenulum of prepuce of penis contained many nerve terminals is an extremely sensitive region. If the frenulum is injured in circumcision or other operations, the complication, such as postoperative spontaneous pain of penis, sexual disturbance and so on, will occur. But there still is no define explanation for this up to now.OBJECTIVE: To observe the distribution of immunoreactive nerve terminal of calcitonin gene-related peptide (CGRP) in prepuce of penis and frenulum of prepuce of adult SD rats, and look for the source of CGRP immunoreactive nerve terminal in frenulum of prepuce.DESIGN: A single sample trial.SETTING:Department of Anatomy, School of Medicine, Zhejiang University.MATERIALS: The

  3. Effects of intracerebroventricular morphine preconditioning on expression of calmodulin in hippocampus,calcitonin gene related peptide in plasma, substance P in hypothalamic paraventricular nucleus and myocardium in myocardial postischemia injury rats%中枢吗啡预处理对心脏缺血后大鼠海马CaM、血浆CGRP以及下丘脑室旁核和心肌P物质表达的影响

    Institute of Scientific and Technical Information of China (English)

    陆姚; 范礼斌; 张野; 翁立军; 李锐; 程新琦; 陈志武

    2009-01-01

    目的 探讨侧脑室内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤的影响及可能的信号机制.方法 建立模型大鼠,随机分为两个部分:①分为4组,每组6只:对照组(CON组),在缺血/再灌注前30 min内,侧脑室内微量泵注射0.9%生理盐水5 min,停止注射5 min,重复3次;预处理组(MPC组),在缺血/再灌注前30 min内,侧脑室内注射吗啡(1 μg·kg-1)5 min,停止5 min,重复3次;钙调蛋白抑制剂三氟拉嗪(trifluoperazine,TFP)+预处理组(TFP+MPC组),在吗啡预处理前10 min一次侧脑室内给予TFP(浓度为20 g·L-1)5 μl;另设TFP自身对照组(TFP组).②分为3组,每组6只:假手术组(Sham组),CON组和MPC组均同第一部分.观察指标包括:平均动脉压(MAP)、心率(HR),计算平均动脉压和心率乘积(RPP);心肌缺血危险区(AAR)、梗死区(IS)的体积、心肌梗死面积以IS/AAR表示;检测血浆降钙素基因相关肽(calcitonin gene related peptide, CGRP);测定海马组织钙调蛋白;测定下丘脑室旁核、心肌缺血区和非缺血区P物质的表达.结果与CON组相比,MPC组的IS和IS/AAR均明显下降(P0.05),而均明显高于MPC组(P<0.01);CON组分别与Sham组和MPC组相比,其下丘脑室旁核、心肌缺血区和非缺血区P物质表达均明显增高(P<0.01,P<0.05);MPC组血浆降钙素基因相关肽CGRP水平与海马钙调蛋白的表达均明显高于其它各组(P<0.01).结论 侧脑室内注射吗啡预处理对在体大鼠心肌缺血/再灌注损伤具有保护作用,其机制可能与钙调蛋白介导释放CGRP和痛觉的干预有关.

  4. 电刺激大鼠上矢状窦区硬脑膜后血浆与脑组织中降钙素基因相关肽、P物质和前列腺素 E2释放差异%Release difference of calcitonin gene-related peptide,substance P and prostaglandin E2 in orbital venous plexus plasma and brain tissues from rats with dura mater of superior sagittal sinus following electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    陈健; 吕新勇; 孙晓萍; 陈春苗; 周军; 王振中; 萧伟

    2014-01-01

    OBJECTIVE Toexplorethefeasibilityofpreparingamigrainemodelusingratdura materofsuperiorsagittalsinusinfollowingelectricalstimulation.METHODS MaleSDratswereexposed to 1 h electrical stimulation after brain electrode implantation,at 3 V,6 Hz,and a pulse of 0.25 ms.At 0, 1 5,30 min,and 1 h,orbital blood and brain tissue were taken.The content of calcitonin gene-related peptide (CGRP),substance P and prostaglandin E2 (PGE2 )in the plas ma and brain tissue was detec-tedbyradioimmunoassay.RESULTS ThebraintissuecontentofCGRP,substancePandPGE2in the sham group and normal group was not significantly different.CGRP,substance P and PGE2 in brain tissue of model group were 3.41 ±0.93,1 .80 ±0.64,3.41 ±0.93 and (1 .80 ±0.64)ng·g -1 respec-tively,significantly different from sham group(P<0.05).At different time points,the content of CGRP, substance P and PGE2 in plasma orbital venous plexus showed no significant difference between sham groupandmodelgroup.CONCLUSION ThereleaseofCGRP,PGE2andsubstancePinbraintissue is significantly different fro m that of plas ma after electrical sti mulation.The results suggest that a model of migraine can be constructed by electrical stimulation.%目的:探讨电刺激大鼠上矢状窦区硬脑膜制备偏头痛模型的可行性。方法雄性SD 大鼠,脑部电极植入术后行电压3 V、频率6 Hz、脉宽0.25 ms、时间1 h电刺激,并于刺激0,15和30 min和1 h进行眼眶采血,采血后取脑组织。采用放射免疫法检测血浆和脑组织中降钙素基因相关肽(CGRP)、P物质和前列腺素E2(PGE2)含量。结果手术对照组与正常对照组大鼠脑组织中 CGRP 含量、P 物质含量和PGE2含量为均无显著性差异;模型组大鼠脑组织中CGRP、P物质和 PGE2分别为3.41±0.93,1.80±0.64和(5.17±0.69)ng·g -1,与手术对照组大鼠相比均有显著性差异(P<0.05)。各时间点手术对照组与模型组大鼠外周

  5. Effects of rizatriptan on calcitonin gene-related peptide, proenkephalin and cholecystokinin mRNA expressions in the trigeminal ganglia of a rat migraine model%利扎曲普坦对偏头痛大鼠三叉神经节降钙素基因相关肽和脑啡肽原及缩胆囊肽基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    姚刚; 郝婷婷; 于挺敏

    2014-01-01

    Objective This study assesses the influence of rizatriptan on calcitonin gene-related peptide (CGRP),proenkephalin (PENK) and cholecystokinin (CCK) mRNA expressions in the trigeminal ganglia of a rat migraine model and investigates the possible mechanisms by which triptans treat migraine.Methods A total of 24 rats were randomly divided into four groups:normal control group (A),migraine model group(B),rizatriptan control group (C) and rizatriptan treatment group(D).Groups C and D were intragastrically perfused with rizatriptan,1 mg/kg per day.After 7 days,nitroglycerin was subcutaneously injected into the buttocks of the groups B and D to induce migraine.Two hours after nitroglycerin injection,the trigeminal ganglia was isolated.CGRP,PENK and CCK mRNA expressions in the trigeminal ganglia were determined using SYBR Green Ⅰ real-time quantitative PCR.Results The copy number of CGRP mRNA (× 107) in 200 ng total RNA of each group was 0.05 ±0.01,1.30 ±0.52,0.23 ±0.12,0.43 ±0.33 ; The copy number of PENK mRNA (× 103) in 200 ng total RNA of each group was 3.30 ± 1.65,0.34 ±0.14,3.91 ± 2.44,0.71 ± 0.13.The copy number of CGRP mRNA in the trigeminal ganglia of group B was significantly higher than that of group A (q =7.854,P < 0.05) ; CGRP mRNA expressions were significantly lower in the trigeminal ganglia of rats in group D compared with group B (q =5.458,P <0.05).Compared with group A,PENK mRNA expressions in the trigeminal ganglia of rats were significantly lower in group B (q =4.478,P < 0.05).PENK mRNA expressions were significantly higher in trigeminal ganglia of rats in group C compared with group D (q =4.838,P < 0.05).CCK mRNA expression in trigeminal ganglia of rats was similar among groups.Conelusions Rizatriptan can decrease the expressions of CGRP in the trigeminal ganglia of the migraine rats and exhibits neurogenic inflammation triggered by CGRP.PENK expressions decrease in the trigeminal ganglia of the migraine rats,weaken the analgesic

  6. Comparison of the effects of salmon calcitonin (sCT) and calcitonin gene-related peptide (CGRP) in a number of in vivo and in vitro tests

    Energy Technology Data Exchange (ETDEWEB)

    Welch, S.P.; Brase, D.; Cooper, C.; Dewey, W.L.

    1986-03-05

    sCT and CGRP have been shown previously to have multiple activities in the central nervous system (CNS). Recent work has shown that CGRP (15 ..mu..g) intraventricularly (IVT) produces a naloxone reversible 37% inhibition in the p-phenylquinone test (PPQ) accompanied by severe diarrhea. The ED50 of sCT in the PPQ test is 362 ng and this effect is not reversed totally by naloxone. The onset of CGRP is more rapid than that of sCT. sCT and CGRP (10/sup -6/M) both produce naloxone reversible inhibition of the electrically stimulated guinea pig ileum (GPI) (25% and 50% respectively). Both sCT and CGRP (10/sup -6/ M) produce contracture (15% and 40% respectively) of the non-stimulated GPI that is not blocked by atropine. Both sCT and CGRP block the naloxone-induced contracture of the morphine (MS04) dependent ilea (29% and 68% respectively). Both sCT and CGRP produce biphasic shifts in the MS04 acetylcholine dose-effect curves in the stimulated and nonstimulated GPI, respectively. Neither sCT nor CGRP (10/sup -9/ to 10/sup -4/ M) displaces /sup 3/H-naloxone binding to mouse brain membranes. Both sCT and CGRP may produce their effects by modulation of CA/sup +2/ fluxes in the CNS and GPI.

  7. 降钙素基因相关肽调控细胞外信号调节激酶减轻高体积分数氧对胎鼠肺泡Ⅱ型上皮细胞的损伤作用%Damage - Reduced Effects of Calcitonin Gene - Related Peptide on Hyperoxia - Exposed Type Ⅱ Alveolar Epithelial Cell Mediated by Extracellular Signal -Regulated Kinase

    Institute of Scientific and Technical Information of China (English)

    付红敏; 李利; 汤春辉; 皇甫春荣; 米弘瑛; 李献珍; 方芳; 许峰

    2012-01-01

    Objective To explore the effects of calcitonin gene - related peptide( CGRF) on type II alveolar epithelial cell( AEC II ) exposed to hyperoxia and whether the mechanism is mediated by extracellular signal - regulated kinase ( ERK) pathway. Methods AEC II were isolated from 21 d fetal rat lung and grew for 12 h to attach. Then AEC II were randomly divided into six groups;air group,CGRP/air group,CGRP8 -37/air group,hyperoxia group,CGRP/O2 and CGRP8 - 37/O2 group. Air or hyperoxia environment was achieved by exposing AEC1I into 210 mL · L-1oxygen or 850 mL · L-1 oxygen for 18 h. CGRP group or CGRP8 - 37 group was carried out by adding 10-1 mol · L-1 CGRP or both CGRP and CGRP8 -37(10-1 mol · L-1) ,a receptor antagonist against CGRP,into medium before cultured in air or 850 mL · I-1 oxygen. Lactate dehydrogenase (LDH) ,alkaline phosphatase (AKP) and malondialdehyde (MDA) were measured by immune tur-bidimetry and reactive oxygen species( ROS) by flow cytometry. Immunofluorescence microscopy was used to analyze the expression of surfactant protein C( SP - C) and Western blot was taken to detect the content of p - ERK1/2. Results The levels of MDA,LDH,AKP,ROS and p-ERKl/2 were markedly increased in hyperoxia group than those in air group [(2. 29 ±0.10) μmol · L-1 vs (1.06±0.14) μmol · L-1, (58.79 ±5.01) U ·L-1 vs (25.92 ±3.68) U · L-1,(24.63 ±2.92) U · L-1 vs (10. 34 ±1.78) U · L-1,47.74 ±3.35 vs 25.96 ±5.04, 1.21 ±0.06 vs 0.45 ±0.05 ,P, <0.01] .whereas expression of SP -C was decreased in hyperoxia group compared with air group (22.75 ±3.31 vs 43. 50 ± 4.42 ). Levels of MDA, LDH, AKP and ROS were reduced with an elevated expression of p - ERK1 /2 and SP - C in CGRP/O2 group compared with those in hyperoxia group and CGRP8 - 37/O2 group (Pa < 0. 01). There were no significant differences about the levels of MDA,LDH,AKP,ROS and SP- C among three groups cultured in air condition. The expression of p - ERK1/2 in CGRP/air group was also higher than

  8. 沙鼠脑缺血再灌注损伤后细胞间黏附分子1及降钙素基因相关肽变化与阿司匹林的干预效应%Effect of aspirin on the expressions of intercellular adhesion molecule 1 and calcitonin-gene-related peptide in gerbils with ischemic reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    刘爽; 李义召; 张涛

    2006-01-01

    .05];而阿司匹林干预组细胞间黏附分子表达水平,在所有时限均明显低于缺血再灌注组,差异有显著性意义[分别为(0.96±0.83)%,(2.76±2.10)%,(1.96±1.09)%,P<0.05].②降钙素基因相关肽表达的变化:在脑缺血再灌注后24 h,3,7 d缺血再灌注组动物降钙素基因相关肽都呈弱阳性表达[分别为(3.12±2.26)%,(2.68±2.04)%,(2.57±1.97)%];而阿司匹林干预组则呈强阳性表达[分别为(4.98±2.47)%,(5.97±2.35)%,(6.04±2.40)%].结论:脑缺血再灌注可诱导细胞间黏附分子1表达上调,并抑制降钙素基因相关肽的表达;阿司匹林通过抑制细胞间黏附分子1表达水平和增强降钙素基因相关肽表达,从而达到较好的脑保护作用.%BACKGROUND: With the development of thrombolysis therapy in recent years, there has been an increasing focus on the protective effect of ischemic reperfusion injury (IRI) and its mechanism at home and abroad,and aspirin is of great importance in the treatment of thrombus diseases owing to its powerful antiplatelet aggregative activity.OBJECTIVE: To explore the protective effect of aspirin on the gerbil brains with IRI and its influence on the intercellular adhesion molecule (ICAM) and calcitonin gene-related peptide (CGRP) expressions.DESIGN: A randomized controlled animal experiments.SETTING: Department of Neurology, Jinan Municipal Central Hospital,College of Clinical Medicine, Shandong University.MATERIALS: The experiment was performed at the Physiological Laboratory of Taishan Medical University from December 2001 to June 2002.Sixty-three healthy male gerbils of Mongolian specimen were randomly assigned into sham group, IRI group and aspirin group with 21 in each group. And each group was further divided into three subgroups according to the time after IRI: 24 hours, 3 days and 7 days, with 7 gerbils for each.METHODS: The models of global brain IRI were established by bilateral carotid artery occlusion. Sham group: The unfolded bilateral

  9. Intermedin and calcitonin gene-related peptide fail to shine in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    K.W. Morrice

    2014-11-01

    Methods and results: 81 patients admitted with suspected ACS were enrolled into the study. 50 were confirmed ACS by ACC (2000 guidelines and 31 were in a control group as non-cardiac chest pain. Intermedin was non-significantly elevated 6.14 pg/ml vs 4.84 pg/ml 8 h after pain onset. The degree of elevation will have limited clinical applicability.

  10. Possible sites of action of the new calcitonin gene-related peptide receptor antagonists

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2010-01-01

    synapses CGRP results in vasodilatation via receptors on the smooth muscle cells. At central synapses, CGRP acts postjunctionally on second-order neurons to transmit pain centrally via the brainstem and midbrain to higher cortical pain regions. The recently developed CGRP-receptor antagonists have...

  11. EXPRESSION OF CALCITONIN GENE-RELATED PEPTIDE IN FACIAL NERVE OF HEMIFACIAL SPASM

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Calcitoningene relatedpeptide(CGRP)enco dedbythecalcitoningeneandcomposedof37ami noacidisabiologicallyactivepolypeptidedetected usinggeneticrecombinationbyRosenfeldin1983.ThemRNAtranscriptedfromcalcitoningenewas translatedintotheCGRPprecursorof128amino acidstoredinthecellularsecretorygranules,then theprecursorwasconvertedenzymaticallyinto CGRPof37aminoacidtoexertitsbiological effect[1].CGRPiswidelydistributedintheperiph eralandcentralnervoussystem,whichsuggestsdi versebiologicalfunctionssuchastheneuralregul...

  12. Blockade of calcitonin gene-related peptide release after superior sagittal sinus stimulation in cat

    DEFF Research Database (Denmark)

    Knight, Y E; Edvinsson, L; Goadsby, P J

    1999-01-01

    . Avitriptan and CP122,288 both have strong binding affinities for 5HT(1B/1D)receptors, but only CP122,288 is a potent inhibitor of PPE. In this study we sought to compare the effects of CP122,288 and avitriptan on jugular vein CGRP release after stimulation of the superior sagittal sinus (SSS) in the cat....... In eleven anaesthetized cats external jugular vein blood samples were analyzed by radioimmunoassay for CGRP levels in three settings: a) control, b) 1 min after SSS stimulation and c) 1 min after SSS stimulation in presence of drug. Stimulation of the SSS resulted in release of CGRP from the external...

  13. CALCITONIN-LIKE IMMUNOREACTIVITY IN SERUM AND TISSUES OF THE BONNETHEAD SHARK, SPHYRNA TIBURO. (R826128)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  14. Kidney Involvement in Systemic Calcitonin Amyloidosis Associated With Medullary Thyroid Carcinoma

    NARCIS (Netherlands)

    Koopman, Timco; Niedlich-den Herder, Cindy; Stegeman, Coen A; Links, Thera P; Bijzet, Johan; Hazenberg, Bouke P C; Diepstra, Arjan

    2016-01-01

    A 52-year-old woman with widely disseminated medullary thyroid carcinoma developed nephrotic syndrome and slowly decreasing kidney function. A kidney biopsy was performed to differentiate between malignancy-associated membranous glomerulopathy and tyrosine kinase inhibitor-induced focal segmental gl

  15. Sumatriptan down-regulates calcitonin gene-related peptide expression via extracellular signalregulated 1/2 and c-Jun N-terminal kinase signaling transduction pathways in rat trigeminal ganglion after organ culture%舒马普坦通过细胞外信号调节激酶1/2和c-Jun氨基末端激酶信号通路下调三叉神经节内降钙素基因相关肽的表达

    Institute of Scientific and Technical Information of China (English)

    罗国刚; 袁博博; 樊文静; 袁兴运; 霍康; 吕社民; 曹永孝; 徐仓宝

    2012-01-01

    Objective To explore the effects of sumatriptan on the modulation of calcitonin generelated peptide(CGRP) expression and its involving intracellular signaling transduction mechanisms in rat trigeminal ganglion(TG) after organ culture.Methods Using organ culture in vitro model,54 isolated TGs of SD rats were randomly divided into fresh group ( n =6 ),control group ( n =6 ) and experimental group (n =42,6 TGs for each subgroup).Experimental group included seven subgroups,which were respectively pretreated with four different concentrations of sumatriptan,specific inhibitors of extracellular signalregulated kinases 1/2 (ERK1/2) pathway (U0126 and PD98059 ),and the inhibitor of c-Jun N-terminal kinase (JNK) (SP600125).After co-cultured with above intervention agents for 24 h,CGRP-immunoreactivity (CGRP-ir) positive neurons and CGRP-mRNA expression levels were quantified by immunohistoehemistry stain and real-time polymerase chain reaction,respectively.Phosphorylated ERK1/2 (pERK1/2) and JNK (pJNK) proteins levels were determined by Western-blotting method.Results The CGRP-ir ( + ) neurons expression levels were significantly increased after 24 h organ culture.However,0.10 and 0.50 mg/ml concentrations of sumatriptan remarkably decreased the CGRP-ir ( + ) neurons expression levels.The positive cell percentage,positive optic area,integrated optical density,mean optical density and CGRP-mRNA expression level in TG were significantly reduced than control groups (tPCP =8.652,26.382; tarea =6.220,13.917; tIA =5.606,15.904; tM14 =2.661,21.748; tmRNA =8.032,15.675.P < 0.05 ).The CGRP-mRNA expressions were significantly down-regulated after co-incubation with concentration of 0.50 mg/ml sumatriptan for 24 h in TG of SD rat ( P <0.05 ).The levels of pERK1/2 and pJNK protein kinase detected by Western-blotting were significantly reduced by 0.50 mg/ml concentration of sumatriptan,the degrees of which were closed to the ERK1/2 and JNK pathway specific blockers.Conclusion It

  16. Sumatriptan does not change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Petersen, Jesper; Wienecke, Troels;

    2009-01-01

    not differ between the four vascular compartments (P=0.49). It was found that Sumatriptan did not change the levels of circulating CGRP in the intra or extracerebral circulation in healthy volunteers. This speaks against a direct CGRP-reducing effect of sumatriptan in vivo in humans when the trigemino...

  17. The Experimental Study on the Effect Calcitonin Gene-related Peptide on Bone Resorption Mediated by Interleukin-1

    Institute of Scientific and Technical Information of China (English)

    LIAN; Kai(

    2001-01-01

    [1]Suda T Udagawa I Nakamura T et al.Modulation of osteoclast? Differentiation by local factors.Bone 1995 17(suppl 2) :875[2]Kanehisa J Heersche J N M.Osteoclastic bone resorption:in vitro analysis of the rate of resorption and migration of individual osteoclasts.Bone 1988 9:73[3]高建军.破骨细胞成熟和活化以及骨吸收机制.内分泌学分册 1998 18(2):57[4]Cohen-Solal M E Granlet A M Denne M A et al.Peripheral blood monocyte culture supernatants of menopausel women can induce bone resorption:involvement of cytokines.J Clin Endocrinol Metab 1993 77:1648[5]Kimble R B Vannice J L Bloedow D C et al.Interleukin-1 receptor antagonist decreases bone loss and bone resorption in ovariectomized rats.J Clin Invest 1994 93:1959[6]Horowitz M C.Cytokines and estrogen in bone:Antiosteoporotic ettects.Science 1993 260:626[7]Thomson B M Saklatvala J Chambers T J et al.Osteoblasts mediate interleukin 1 stimulation of bone resorption by rat osteoclasts.J Exp Med 1986 164:104[8]Goltzman D Mitchell J.Interaction of calciton and CGRP at receptor sites in target tissue.Science 1985 227:1343[9]Millet I Vignery A.The neuropeptide CGRP inhibits TNF-α but poorly induces IL-6 production by fetal rat osteoblasts.Cytokine 1997 12(9):999[10]Taichman R S Hauschka P V.Effects of IL-1βand TNF-α on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro.Inflammation.1992 16:587

  18. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats

    DEFF Research Database (Denmark)

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V

    2014-01-01

    study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ....... Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma...... food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action...

  19. The role of calcium in endotoxin-induced release of calcitonin gene-related peptide (CGRP) from rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    唐跃明; 韩启德; 王宪

    1997-01-01

    In the present study, the role of calcium in endotoxin-induced CGRP release was studied. 2 .5-50 μg/mL endotoxin and 1 -10 mmol/L caffeine caused concentration-dependent increase of CGRP release from rat spinal cord in vitro. However, no additive effect could he found when caffeine and endotoxin were concomitantly incubated. By using capsaicin, Ca2+-free medium, Omega-Conotoxin, nifedipine, W-7, ryanodine, MgCl2, Tris-ATP, rutheni-um red, the results indicate that the release of CGRP evoked by endotoxin from the sensory fibers of rat spinal cord is dependent on extracellular calcium. After entering into the cell through the N-type calcium channel, calcium binds to calmodulin, and triggers calcium release from intracellular calcium store by activating the caffeine-sensitive but ryan-odine-insensitive mechanism.

  20. Transcerebral exchange kinetics of nitrite and calcitonin gene-related peptide in acute mountain sickness: evidence against trigeminovascular activation?

    DEFF Research Database (Denmark)

    Bailey, Damian M; Taudorf, Sarah; Berg, Ronan M G;

    2009-01-01

    BACKGROUND AND PURPOSE: High-altitude headache is the primary symptom associated with acute mountain sickness, which may be caused by nitric oxide-mediated activation o