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Sample records for calcitonin

  1. Calcitonin Salmon Nasal Spray

    Science.gov (United States)

    ... pump is now primed. To use the nasal spray, follow these steps: Keep your head up and place the nozzle in one nostril. Press down on the pump ... reach of children. Store unopened calcitonin salmon nasal spray in the ... the nozzle clean. Opened calcitonin salmon stored at room temperature ...

  2. 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.

  3. Calcitonin

    Science.gov (United States)

    ... few minutes to measure the effect of the stimulation. People with early C-cell hyperplasia and/or medullary thyroid cancer ... with thyroid nodules, but not all clinicians agree. Stimulation tests may be ... 2, starting at an early age, in order to detect medullary thyroid cancer ...

  4. 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 the...... 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...

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.

  8. 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.

  9. Stimulation of calcitonin secretory capacity by increased serum levels of testosterone in men treated with tamoxifen.

    Science.gov (United States)

    Schopman, W; Slager, E; Hackeng, W H; Mulder, H

    1987-12-01

    Previous studies have suggested that sex steroids, including both oestrogen and testosterone, influence calcitonin secretion. However, a negative effect of gonadotrophins on calcitonin has not been excluded. Twelve men with infertility and low-normal serum levels of testosterone were studied before and during tamoxifen therapy. Increases in the serum levels of LH, FSH, testosterone and calcitonin were observed after treatment. Our findings suggest that testosterone has a direct influence on calcitonin secretion. PMID:3123401

  10. [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. PMID:2576918

  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 and adrenomedullin release in humans

    DEFF Research Database (Denmark)

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

    2002-01-01

    Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are potent vasorelaxant peptides. This study examined exercise-induced changes in CGRP and AM levels in 12 healthy sea level natives at sea level (SL) and subsequently after 24 h (HA1) and 5 days (HA5) in high altitude hypoxia (4559 m......). 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...

  13. Calcitonin-negative neuroendocrine tumor of thyroid gland mimicking anaplastic carcinoma: an unusual entity

    Science.gov (United States)

    Arpaci, Rabia Bozdogan; Berkesoglu, Mustafa; Dag, Ahmet; Sezer, Emel; Bal, Kemal Koray; Vayısoğlu, Yusuf

    2015-01-01

    Medullary thyroid cancer is the neuroendocrine tumor (NET) of thyroid with mostly both secreting calcitonin and immunohistochemically showing calcitonin positivity. Occasionally; NETs of thyroid may have little or no calcitonin expression. We present a case of serum calcitonin negative and immunohistochemically calcitonin-negative staining tumor with positive reaction to neuroendocrine markers synaptophysin and chromogranin-A. The patient’s right vocal cord was paralytic and thyroid mass was huge with descending to thorax till hilar region. We discussed diagnostic difficulties and way of treatment about NETs of thyroid with the light of current literature with this case. PMID:26312221

  14. The Treatment of Sudeck Syndrorn or Algodystrophie by Calcitonin

    OpenAIRE

    Breintenfelder, J.; Yucel, M

    2004-01-01

    The treatment of the Sudeck Syndrome, basing upon different points of view is to the essence of this sickness, is ambiguous and even contradictory. Assuming to experiences obtained in the treatment of aigodistrophies, we shall try to set up a generally valid scheme of treatment, according to case descriptions. The method involved empioys calcitonin.

  15. 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 §...

  16. Osteoblast hydraulic conductivity is regulated by calcitonin and parathyroid hormone

    Science.gov (United States)

    Hillsley, M. V.; Frangos, J. A.

    1996-01-01

    It is our hypothesis that osteoblasts play a major role in regulating bone (re)modeling by regulating interstitial fluid (ISF) flow through individual bone compartments. We hypothesize that osteoblasts of the blood-bone membrane lining the bone surfaces are capable of regulating transosseous fluid flow. This regulatory function of the osteoblasts was tested in vitro by culturing a layer of rat calvarial osteoblasts on porous membranes. Such a layer of osteoblasts subjected to 7.3 mm Hg of hydrostatic pressure posed a significant resistance to fluid flow across the cell layer similar in magnitude to the resistance posed by endothelial monolayers in vitro. The hydraulic conductivity, the volumetric fluid flux per unit pressure drop, of the osteoblast layer was altered in response to certain hormones. Hydraulic conductivity decreased approximately 40% in response to 33 nM parathyroid hormone, while it exhibited biphasic behavior in response to calcitonin: increased 40% in response to 100 nM calcitonin and decreased 40% in response to 1000 nM calcitonin. Further, activation of adenylate cyclase by forskolin dramatically increased the hydraulic conductivity, while elevation of intracellular calcium, [Ca2+]i, by the calcium ionophore A23187 initially decreased the hydraulic conductivity at 5 minutes before increasing conductivity by 30 minutes. These results suggest that cyclic adenosine monophosphate (cAMP) and [Ca2+]i may mediate changes in the osteoblast hydraulic conductivity. The increase in hydraulic conductivity in response to 100 nM calcitonin and the decrease in response to PTH suggest that the stimulatory and inhibitory effects on bone formation of calcitonin and parathyroid hormone, respectively, may be due in part to alterations in bone fluid flow.

  17. Circulating parathyroid hormone and calcitonin in rats after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Fung, Paul; Popova, Irina A.; Morey-Holton, Emily R.; Grindeland, Richard E.

    1992-01-01

    Parathyroid hormone and calcithonin, two major calcium-regulating hormones, were measured in the plasma of five experimental groups of rats to evaluate postflight calcium homeostasis after the 14-day Cosmos 2044 flight. Parathyroid hormone values were slightly higher in the flight animals (F) than in the appropriate cage and diet controls (S) (44 +/- 21 vs 21 +/- 4 pg/ml, P less than 0.05), but they were the same as in the vivarium controls (V), which had different housing and feeding schedules. The difference in F and V (22 +/- 11 vs 49 +/- 16 pg/ml, P less than 0.05) was most likely due to failure of circulating calcitonin in F to show the normal age-dependent increase which was demonstrated in age-matched controls in a separate experiment. Basal values for parathyroid hormone and calcitonin were unchanged after 2 wk of hindlimb suspension, a flight simulation model, in age-matched and younger rats. From a time course experiment serum calcium was higher and parathyroid hormone lower after 4 wk than in ambulatory controls. Postflight circulating levels of parathyroid hormone appear to reflect disturbances in calcium homeostasis from impaired renal function of undetermined cause, whereas levels of calcitonin reflect depression of a normal growth process.

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

    International Nuclear Information System (INIS)

    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(φ) and S(ψ) 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 α-helices, are likely to be represented by left-handed α-helices

  19. 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

  20. 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.

  1. 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.

  2. Decrease of serum testosterone by cyproterone acetate accompanied by an unexpected increase of calcitonin secretion capacity.

    Science.gov (United States)

    Mulder, H; Eland, D; Hackeng, W H; Schopman, W

    1987-08-01

    The interaction between testosterone and calcitonin secretion capacity was studied in 9 patients with prostatic cancer. Treatment with the antiandrogenic agent cyproterone acetate resulted in an expected decrease in serum testosterone but an unexpected and unexplained increase in calcitonin secretion capacity. The previous statement that a positive correlation between sex hormones and calcitonin secretion capacity can be recognized probably requires revision. This unexpected effect of cyproterone acetate had possible additive beneficial advantages for treatment, such as bone mass sparing and its analgesic effect. PMID:2955132

  3. Calcitonin gene-related peptide and migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Ashina, Messoud

    2014-01-01

    levels of CGRP in MA patients are comparable to MO, but CGRP levels varied among studies. A number of animal studies, including knock-ins of familial hemiplegic migraine (FHM) genes, have examined the relationship between CGRP and cortical spreading depression. In patients, CGRP does not trigger migraine......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...... in FHM, but is a robust trigger of migraine-like headache both in MA and MO patients. The treatment effect of CGRP antagonists are well proven in the treatment of migraine, but no studies have studied the effect specifically in MA patients. CONCLUSION: This systematic review indicates that the role...

  4. Involvement of calcitonin gene-related peptide in migraine

    DEFF Research Database (Denmark)

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

    2008-01-01

    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...... 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...

  5. Optimizing the radioimmunologic determination methods for cortisol and calcitonin

    International Nuclear Information System (INIS)

    In order to build up a specific 125-iodine cortisol radioimmunoassay (RIA) pure cortisol-3(0-carbodxymethyl) oxim was synthesized for teh production of antigens and tracers. The cortisol was coupled with tyrosin methylester and then labelled with 125-iodine. For the antigen production the cortisol derivate was coupled with the same method to thyreoglobulin. The major part of the antisera, which were obtained like this, presented high titres. Apart from a high specificity for cortisol a high affinity was found in the acid pH-area and quantified with a particularly developed computer program. An extractive step in the cortisol RIA could be prevented by efforts. The assay was carried out with an optimized double antibody principle: The reaction time between the first and the second antiserum was considerably accelerated by the administration of polyaethylenglycol. The assay can be carried out automatically by applying a modular analysis system, which operates fast and provides a large capacity. The required quality and accuracy controls were done. The comparison of this assay with other cortisol-RIA showed good correlation. The RIA for human clacitonin was improved. For separating bound and freely mobile hormones the optimized double-antibody technique was applied. The antiserum was examined with respect to its affinity to calcitonin. For the 'zero serum' production the Florisil extraction method was used. The criteria of the quality and accuracy controls were complied. Significantly increased calcitonin concentrations were found in a patient group with medullar thyroid carcinoma and in two patients with an additional phaechromocytoma. (orig./MG)

  6. [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.

  7. Activation of multiple mitogen-activated protein kinases by recombinant calcitonin gene-related peptide receptor.

    Science.gov (United States)

    Parameswaran, N; Disa, J; Spielman, W S; Brooks, D P; Nambi, P; Aiyar, N

    2000-02-18

    Calcitonin gene-related peptide is a 37-amino-acid neuropeptide and a potent vasodilator. Although calcitonin gene-related peptide has been shown to have a number of effects in a variety of systems, the mechanisms of action and the intracellular signaling pathways, especially the regulation of mitogen-activated protien kinase (MAPK) pathway, is not known. In the present study we investigated the role of calcitonin gene-related peptide in the regulation of MAPKs in human embryonic kidney (HEK) 293 cells stably transfected with a recombinant porcine calcitonin gene-related peptide-1 receptor. Calcitonin gene-related peptide caused a significant dose-dependent increase in cAMP response and the effect was inhibited by calcitonin gene-related peptide(8-37), the calcitonin gene-related peptide-receptor antagonist. Calcitonin gene-related peptide also caused a time- and concentration-dependent increase in extracellular signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (P38 MAPK) activities, with apparently no significant change in cjun-N-terminal kinase (JNK) activity. Forskolin, a direct activator of adenylyl cyclase also stimulated ERK and P38 activities in these cells suggesting the invovement of cAMP in this process. Calcitonin gene-related peptide-stimulated ERK and P38 MAPK activities were inhibited significantly by calcitonin gene-related peptide receptor antagonist, calcitonin gene-related peptide-(8-37) suggesting the involvement of calcitonin gene-related peptide-1 receptor. Preincubation of the cells with the cAMP-dependent protein kinase inhibitor, H89 [¿N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide, hydrochloride¿] inhibited calcitonin gene-related peptide-mediated activation of ERK and p38 kinases. On the other hand, preincubation of the cells with wortmannin ¿[1S-(1alpha,6balpha,9abeta,11alpha, 11bbeta)]-11-(acetyloxy)-1,6b,7,8,9a,10,11, 11b-octahydro-1-(methoxymethyl)-9a,11b-dimethyl-3H-furo[4,3, 2-de]indeno[4,5-h]-2

  8. Radioimmunological investigation of calcitonine in patients with reccurent calcium nephrolithiasis before and after calcium loading

    International Nuclear Information System (INIS)

    The diagnostic value of the changes in the calcitonine serum levels for differentiation of different types of hypercalciuria was assessed. The investigation was carried out with 15 patients with recurrent calcium nephrolithiasis and hypercalciuria, 4 - with primary hyperparathyroidism, 3 - with renal hypercalciuria, 7 - with absorptive hypercalciuria and 1 -with adenomectomy of the parathyroid glands. The calcitonine serum was determined before and after loading with 1000 mg Ca. A double-antibody radioimmunological method with high specificity, accuracy and sensitivity was used for calcitonine determination. The results of the study revealed that the serum calcitonine cannot serve as differential diagnostic criterion in determination of the type of hypercalciuria, but could be useful in the diagnosis of the medullary cancer of the thyroid gland. 3 figs., 5 refs

  9. Transient receptor potential channel A1 involved in calcitonin gene-related peptide release in neurons

    Institute of Scientific and Technical Information of China (English)

    Nobumasa Ushio; Yi Dai; Shenglan Wang; Tetsuo Fukuoka; Koichi Noguchi

    2013-01-01

    Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of al yl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock-down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by al yl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.

  10. Contributions of calcitonin gene-related peptide in ischemia, inflammation and nociception

    OpenAIRE

    Brodda Jansen, Gunilla

    1996-01-01

    The sensory neuropeptide Calcitonin gene-related peptide (CGRP) is a very potent vaso- dilator with a wide distribution in peripheral sensory nerves, often co-stored with sub- stance P. In the present study, the effects of CGRP in different models of ischemia, inflammation and nociception were examined. Calcitonin gene-related peptide, but not substance P (SP), was found to inhibit edema-promoting actions of inflammatory mediators (histamine, leukotrine B4, 5-hydroxytryp...

  11. 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

  12. 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

  13. 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.

  14. 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....

  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. 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.

  17. 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.

  18. 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

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

    OpenAIRE

    Emilia Angela Loschiavo Arisawa; Janete Dias Almeida; Raduan Hage; Claúdia Alessandra Cardoso; Tatiana Pinto Ribeiro; Simone Bustamante Nascimento

    2012-01-01

    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 w...

  20. 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....

  1. 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. PMID:24599901

  2. 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.

  3. Novel migraine therapy with calcitonin gene-regulated peptide receptor antagonists

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2007-01-01

    Primary headaches, for example, migraine and cluster headaches represent the most prevalent neurological disorders, affecting up to 15-20% of the adult population. There is a clear association between head pain and the release of calcitonin gene-related peptide (CGRP). In this review the role...... and that they are not vasoconstrictive, providing a new dimension in therapy....

  4. Human medullary thyroid carcinoma: cell cultures and xenotransplants in nude mice. Immunocytochemistry and calcitonin secretion.

    Science.gov (United States)

    Andry, G; Lothaire, P; Vico, P; Dumont, P; Libert, A; Degeyter, M; Larsimont, D; Saigo, P E; Body, J J; Atassi, G

    1989-12-01

    Occult primary and recurrent medullary thyroid carcinomas (MTC) detected only by elevated calcitonin levels in the peripheral blood, generally after pentagastrin-test stimulation, are difficult to localize. Some new imaging procedures with radionuclide tracers or radiolabelled monoclonal antibodies against carcinoembryonic antigen seem to bring some potentially therapeutic benefits. We report our results with cell cultures and xenotransplants of human MTC with the intention of establishing reproducible models in vitro and in vivo. Cell cultures secrete calcitonin at up to 1200 pg/ml for periods ranging from 3 to 13 weeks. Immunocytochemistry detects cytoplasmic granules positive for calcitonin in polygonal epithelioid cells with dendritic processes. Xenotransplants in nude mice fare better in the subcutaneous axilla than in the subrenal capsule assay. In the former location the tumor-take is good and calcitonin is detected in the blood of the tumor-bearing animals, at levels ranging from 286 to more than 20,000 pg/ml. These models would be potentially usable as targets for radionuclide tracers and/or radiolabelled monoclonal antibodies. PMID:2689238

  5. 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.)

  6. Enhanced vasodilator responses to calcitonin gene-related peptide (CGRP) in subcutaneous arteries in human hypertension

    DEFF Research Database (Denmark)

    Lind, H; Edvinsson, L

    2002-01-01

    Isolated segments (1-2 mm) of small subcutaneous arteries (diameter 0.1-0.9 mm) and veins (0.1-1.0 mm) from patients with hypertension (essential n = 13, renovascular n = 6) and controls (n = 17) were examined. The relaxant responses to the sensory transmitters calcitonin gene-related peptide (CGRP...

  7. 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.

  8. 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.

  9. 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

  10. Clinical evaluation of radioassays for calcitonin, CEA-S, AFP and ferritin as tumor markers

    International Nuclear Information System (INIS)

    Clinical usefulness of the radioassays for serum calcitonin, isometric species of carcinoembryonic antigen (CEA-S), alpha-fetoprotein (AFP) and ferritin as the specific tumor markers was evaluated. The calcitonin assay was found to be extremely useful in detecting the cases of familial medullary carcinoma of the thyroid and in monitoring the patients after surgery. The CEA-S assay was proved more specific in titers and positivity for malignancies, especially GI tract carcinomas than CEA assay. The diagnosis of hepatoma could be performed precisely with a combination of 67Ga scintigraphy and assays of CEA and AFP. The serum ferritin levels in malignancies overlapped widely with those of non-malignancies. However, the estimation of ferritin-iron ratio was thought to be a useful means for screening patients with suspicious lesions. (author)

  11. 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

    .58). Headache severity and intensity were not different between the groups. Conclusions: Familial hemiplegic migraine ( FHM) patients do not show hypersensitivity of the calcitonin gene-related peptide (CGRP)-cyclic adenosine 3 ', 5 '-monophosphate pathway, as characteristically seen in migraine patients......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...... 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...

  12. Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

    OpenAIRE

    Tozzi, A; A. De Iure; di Filippo, M.; Costa, C.; Caproni, S.; Pisani, A.; Bonsi, P.; B. Picconi; Cupini, L. M.; Materazzi, S.; Geppetti, P.; Sarchielli, P; Calabresi, P.

    2012-01-01

    Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investig...

  13. Effects of calcitonin and calcium medication in treatment of edentulous osteoporotic mandible

    OpenAIRE

    Poštić Srđan D.

    2013-01-01

    Background/Aim. In addition to damage of the bones that support the remaining teeth, degradation of osteoporotic oral bones also lead to a consequent reduction of supporting tissues and the loss of dentures retention. The aim of this study was to assess the clinical and radiographic outcomes following injection of a calcitonin and calcium solution into the buccal aspects of edentulous mandibles. Methods. The experimental group of 67 edentulous patients diagnosed with osteoporosis, and t...

  14. 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....

  15. 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

    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...

  16. 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.

  17. [Summary of work session 4: Effects of calcitonin and somatostatin on the stomach and pancreas--a possible therapeutic principle].

    Science.gov (United States)

    Goebell, H; Hotz, J

    1976-03-01

    Although calcitonin and somatostatin are polypeptid hormones of entirely different structure, in pharmacological doses they possess a similar effect to secretions of stomach and pancreas. Given intravenously, they generally inhibit the basal secretion of organs, stimulated by pentagastrin or pancreozymin, as well as the contraction of the gallbladder. Orally, calcitonin also suppresses by direct contact the secretion of the stomach. While calcitonin in higher doses shows only very slight and tolerable side effects (nausea, headache), somatostatin acts suppressively on many other hormone-regulated systems. Apart from this, disturbances of blood coagulation in monkeys and man were observed, findings which necessitate very careful application. Therapeutical trials appear reasonable with calcitonin in treating acute pancreatitis, in prophylaxis and treatment of stress ulcers with the danger of bleeding, in intensive care medicine, in preoperative procedure of Zollinger-Ellison syndrome as well as in duodenal ulcers (oral calcitonin). Double blind studies are carried out at present to answer most of these questions (acute pancreatitis, stress ulcers, duodenal ulcers), results of which should definitely be awaited.

  18. 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

    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 o......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 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 a...

  19. 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....

  20. 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.

  1. Refractory hypercalcemia and ectopic calcitonin secretion in a malignant pancreatic neuroendocrine tumor: hypocalcemic effects on cinacalcet

    OpenAIRE

    Valdes Socin, Hernan Gonzalo; Rubio Almanza, Matilde; LOLY, Jean-Philippe; Polus, Marc; Beckers, Albert

    2013-01-01

    Introduction: Paraneoplastic hypercalcemia is a sign of poor prognosis, as it is particularly resistant to the usual hypocalcemic treatments. Observation: In 2009, a well differentiated pancreatic neuroendocrine tumor (Ki-67= 2%) is diagnosed in a 52-year-old diabetic man. The tumor is revealed with a splenic and hepatic carcinomatosis. Plasmatic calcium was: 3.54 mmol/L (2.15 - 2.6). Biology showed hypophosphatemia, PTH < 4 ng/ml, high 1-25 OH VitD, calcitonin: 1016 ng/ml (< 12 ng/ml). H...

  2. 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, Jes;

    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....

  3. Secretion of calcitonin and gastrin in rats with transplanted medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Rats transplanted with medullary thyroid carcinoma (MCT) were followed with radio-immuno assay of serum calcitonin (iCT) using antisera to human CT and I125 labelled calcitonin-M. From the 4th month after transplantation, serum from the tumour rats contained iCT in concentrations 8-10 fold higher than serum from the control rats. The tumour cells had retained their ability to react on pentagastrin and calcium injections with increased CT release. It was further shown that the tumour bearing rats had elevated basal gastrin concentrations in serum. While calcium injection lead to a rise in the serum gastrin concentration in the control group, the adverse effect was seen in the tumour bearing rats. The morphological features and the responsiveness of the rat tumour cells to physiological secretagogues make this tumour a suitable animal model for the study of interactions between CT and gastro-intestinal factors. It is suggested that the gastrin response to calcium might be of interest also in the diagnosis of human MCT. (author)

  4. Calcitonin gene-related peptide (CGRP receptors are important to maintain cerebrovascular reactivity in chronic hypertension.

    Directory of Open Access Journals (Sweden)

    Zhenghui Wang

    Full Text Available Cerebral blood flow autoregulation (CA shifts to higher blood pressures in chronic hypertensive patients, which increases their risk for brain damage. Although cerebral vascular smooth muscle cells express the potent vasodilatatory peptides calcitonin gene-related peptide (CGRP and adrenomedullin (AM and their receptors (calcitonin receptor-like receptor (Calclr, receptor-modifying proteins (RAMP 1 and 2, their contribution to CA during chronic hypertension is poorly understood. Here we report that chronic (10 weeks hypertensive (one-kidney-one-clip-method mice overexpressing the Calclr in smooth muscle cells (CLR-tg, which increases the natural sensitivity of the brain vasculature to CGRP and AM show significantly better blood pressure drop-induced cerebrovascular reactivity than wt controls. Compared to sham mice, this was paralleled by increased cerebral CGRP-binding sites (receptor autoradiography, significantly in CLR-tg but not wt mice. AM-binding sites remained unchanged. Whereas hypertension did not alter RAMP-1 expression (droplet digital (dd PCR in either mouse line, RAMP-2 expression dropped significantly in both mouse lines by about 65%. Moreover, in wt only Calclr expression was reduced by about 70% parallel to an increase of smooth muscle actin (Acta2 expression. Thus, chronic hypertension induces a stoichiometric shift between CGRP and AM receptors in favor of the CGRP receptor. However, the parallel reduction of Calclr expression observed in wt mice but not CLR-tg mice appears to be a key mechanism in chronic hypertension impairing cerebrovascular reactivity.

  5. 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

  6. 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....

  7. 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...

  8. Calcitonin gene-related peptide and its receptor components in the human sphenopalatine ganglion -- interaction with the sensory system

    DEFF Research Database (Denmark)

    Csati, Anett; Tajti, Janos; Tuka, Bernadett;

    2012-01-01

    Clinical studies have suggested a link between the sensory trigeminal system and the parasympathetic ganglia. Calcitonin gene-related peptide (CGRP) is a sensory neuropeptide which plays an important role in vasodilatation and pain transmission in craniocervical structures. The present study was ...

  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. Effect of estradiol-17β on calcitonin receptor bindings in the hen neurohypophysis.

    Science.gov (United States)

    Nakayama, H; Takahashi, T; Nakagawa-Mizuyachi, K; Kawashima, M

    2011-01-01

    The present study was performed to elucidate whether estradiol-17β (E₂) would affect calcitonin (CT) receptor binding in the hen neurohypophysis. The equilibrium dissociation constant (K(d)) and the maximum binding capacity (B(max)) of the CT receptor in the plasma membrane fraction of the hen neurohypophysis were examined by Scatchard analysis of specific binding of (125)I-labeled chicken CT. A single i.m. injection of E₂ into nonlaying hens caused a decrease in K(d) and B(max) values of the CT receptor. The K(d) and B(max) values of the CT receptor were smaller in laying hens than in nonlaying hens. The present study suggests that E₂ may increase the action of CT on the neurohypophysis in hens. PMID:21177459

  11. Calcitonin receptor binding properties in bone and kidney of the chicken during the oviposition cycle.

    Science.gov (United States)

    Yasuoka, T; Kawashima, M; Takahashi, T; Tatematsu, N; Tanaka, K

    1998-09-01

    The binding property of calcitonin (CT) in the membrane fraction of calvaria and kidney of egg-laying and nonlaying hens was analyzed using a [125I] CT binding assay system. Binding properties of CT receptors in both tissues satisfy the authentic criteria of a receptor-ligand interaction in terms of specificity, reversibility, and saturation. Scatchard plots revealed a single class of binding sites. Values of the equilibrium dissociation constant (Kd) and binding capacity (Bmax) in laying hens showed a decrease during the period between 3 h before and 2 h after oviposition. No change was observed in nonlaying hens. In vivo administration of 17beta-estradiol or progesterone caused the decrease in Kd and Bmax values. The results suggest that the binding affinity and capacity of the CT receptor in the calvaria and the kidney of the hen may be modulated by the ovarian steroid hormone. PMID:9738513

  12. Synovial macrophage-derived IL-1β regulates the calcitonin receptor in osteoarthritic mice.

    Science.gov (United States)

    Takano, S; Uchida, K; Miyagi, M; Inoue, G; Aikawa, J; Fujimaki, H; Minatani, A; Sato, M; Iwabuchi, K; Takaso, M

    2016-01-01

    Recent studies have reported that calcitonin gene-related peptide (CGRP) contributes to joint pain. However, regulation of the CGRP/CGRP receptor signalling in osteoarthritis (OA) is not fully understood. To investigate the regulation of CGRP/CGRP receptor signalling by macrophages in the synovial tissue (ST) of OA joints, we characterized the gene expression profiles of CGRP and CGRP receptors in the ST of OA mice (STR/Ort). In addition, we examined whether macrophage depletion by the systemic injection of clodronate-laden liposomes affected the expression of CGRP and CGRP receptors in ST. CD11c(+) macrophages in the ST of STR/Ort and C57BL/6J mice were analysed by flow cytometry. Real-time polymerase chain reaction (PCR) was used to evaluate the expression of interleukin (IL)-1β, CGRP, calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in F4/80(+) and F4/80(-) cells. The effects of IL-1β on the expression of CGRP and CLR by cultured synovial cells were also examined. The percentage of CD11c(+) macrophages in the ST of STR/Ort was higher than that in C57/BL6J mice. Notably, the F4/80(+) cell fraction expressed IL-1β highly, whereas the F4/80(-) cell fraction expressed CGRP, CLR, and RAMP1 highly. In addition, expression of the IL-1β and CLR genes was increased in ST, but was decreased upon macrophage depletion, and the IL-1β treatment of cultured synovial cells up-regulated CLR. Taken together, the present findings suggest that synovial macrophages are the major producers of IL-1β and regulators of CLR in OA mice. Therefore, macrophages and IL-1β may be suitable therapeutic targets for treating OA pain. PMID:26400621

  13. 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.

  14. Identification of calcitonin expression in the chicken ovary: influence of follicular maturation and ovarian steroids.

    Science.gov (United States)

    Krzysik-Walker, Susan M; Ocón-Grove, Olga M; Maddineni, Sreenivasa B; Hendricks, Gilbert L; Ramachandran, Ramesh

    2007-10-01

    Calcitonin (CALCA), a hormone primarily known for its role in calcium homeostasis, has recently been linked to reproduction, specifically as a marker for embryo implantation in the uterus. Although CALCA expression has been documented in several tissues, there has been no report of production of CALCA in the ovary of any vertebrate species. We hypothesized that the Calca gene is expressed in the chicken ovary, and its expression will be altered by follicular maturation or gonadal steroid administration. Using RT-PCR, we detected Calca mRNA and the calcitonin receptor (Calcr) mRNA in the granulosa and theca layers of preovulatory and prehierarchial follicles. Both CALCA and Calca mRNA were localized in granulosa and thecal cells by confocal microscopy. Using quantitative PCR analysis, F1 follicle granulosa layer was found to contain significantly greater Calca mRNA and Calcr mRNA levels compared with those of any other preovulatory or prehierarchial follicle. The granulosa layer contained relatively greater Calca and Calcr mRNA levels compared with the thecal layer in both prehierarchial and preovulatory follicles. Progesterone (P(4)) treatment of sexually immature chickens resulted in a significantly greater abundance of ovarian Calca mRNA, whereas estradiol (E(2)) or P(4) + E(2) treatment significantly reduced ovarian Calca mRNA quantity. Treatment of prehierarchial follicular granulosa cells in vitro with CALCA significantly decreased FSH-stimulated cellular viability. Collectively, our results indicate that follicular maturation and gonadal steroids influence Calca and Calcr gene expression in the chicken ovary. We conclude that ovarian CALCA is possibly involved in regulating follicular maturation in the chicken ovary. PMID:17582014

  15. 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

    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...... were classified correctly initially. The sensitivity of serum calcitonin for detection of MTC was 100%, the specificity was 95.3%, the positive predictive value was 15.4%, and the negative predictive value was 100%. CONCLUSION: Serum calcitonin has high sensitivity and specificity for detection of MTC....... 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....

  16. 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.

  17. Cerebroventricular calcitonin gene-related peptide inhibits rat duodenal bicarbonate secretion by release of norepinephrine and vasopressin.

    OpenAIRE

    Lenz, H. J.; Brown, M R

    1990-01-01

    Proximal duodenal bicarbonate secretion is an important factor in humans and animals protecting the mucosa against acid-peptic damage. This study examined the mechanisms responsible for the central nervous system regulation of duodenal bicarbonate secretion by calcitonin gene-related peptide (CGRP) in unrestrained rats. Cerebroventricular administration of rat CGRP significantly inhibited basal duodenal bicarbonate secretion as well as the stimulatory effects of vasoactive intestinal peptide,...

  18. Regional haemodynamic effects of prolonged infusions of human alpha-calcitonin gene-related peptide in conscious, Long Evans rats.

    OpenAIRE

    Gardiner, S. M.; Compton, A. M.; P A Kemp; Bennett, T; Foulkes, R; Hughes, B.

    1991-01-01

    1. Haemodynamic measurements were made in conscious, Long Evans rats chronically instrumented for the assessment of changes in regional blood flows (renal, mesenteric and hindquarters, or internal and common carotid) and systemic arterial blood pressure and heart rate, before, during and after 3 day infusions of vehicle or human alpha-calcitonin gene-related peptide (CGRP) (1.5 or 15 nmol kg-1 h-1). 2. In animals with renal, mesenteric and hindquarters flow probes (n = 8), during the first da...

  19. Expression of Calcitonin Gene-Related Peptide in Efferent Vestibular System and Vestibular Nucleus in Rats with Motion Sickness

    OpenAIRE

    Wang Xiaocheng; Shi Zhaohui; Xue Junhui; Zhang Lei; Feng Lining; Zhang Zuoming

    2012-01-01

    UNLABELLED: Motion sickness presents a challenge due to its high incidence and unknown pathogenesis although it is a known fact that a functioning vestibular system is essential for the perception of motion sickness. Recent studies show that the efferent vestibular neurons contain calcitonin gene-related peptide (CGRP). It is a possibility that the CGRP immunoreactivity (CGRPi) fibers of the efferent vestibular system modulate primary afferent input into the central nervous system; thus, maki...

  20. Investigation of bone and mineral metabolism in hyperthyroidism before and after treatment using calcitonin, 47Ca and balance studies

    International Nuclear Information System (INIS)

    Seventeen normocalcaemic patients with severe hyperthyroidism were examined before therapy was initiated; 9 were re-examined about 1 year later. Studies with 47Ca under balance conditions and with calcitonin demonstrated a high rate of bone resorption in untreated patients. As a result of the increased bone turnover, the reaction to 6 MRC units of porcine calcitonin iv was more marked in the untreated than in the treated patients, or the control group. In contrast to the normal diurnal pattern for PO4, it was found that during fasting the plasma PO4 level increases in the morning in patients with hyperthyroidism. This increase which was not suppressed by the administered dose of calcitonin developed in spite of an elevated urinary PO4 excretion. After treatment, the serum Ca concentration as well as the urinary and faecal Ca excretion was decreased. The Ca balance improved; the rapidly-exchangeable Ca pool returned to normal. The slowly-exchangeable and the total Ca pools, however, remained enlarged. The rate of bone resorption normalized. The accretion rate on the other hand remained elevated. This is attributed to continued enhancement of bone formation to compensate for the previous loss of bony tissue. (author)

  1. Reference values of serum calcitonin with calcium stimulation tests by electrochemiluminescence immunoassay before/after total thyroidectomy in Japanese patients with thyroid diseases other than medullary thyroid carcinoma.

    Science.gov (United States)

    Kihara, Minoru; Miyauchi, Akira; Kudo, Takumi; Hirokawa, Mitsuyoshi; Miya, Akihiro

    2016-07-30

    Calcitonin is a very sensitive tumor marker of medullary thyroid carcinoma (MTC). MTC patients usually have very high values of serum calcitonin that can be used to diagnose the disease. To improve the diagnostic sensitivity in family members with small MTCs and to evaluate the postoperative biochemical cure status, a calcium stimulation test is widely used. Serum calcitonin has been measured using several methods, but in Japan, only an electrochemiluminescence immunoassay (ECLIA) is currently performed to determine serum calcitonin. Reference values for the calcium stimulation test using an ECLIA have not been reported. Here we conducted a calcium stimulation tests in 26 patients without MTC before and after total thyroidectomy. Preoperatively, the basal calcitonin values of all patients were within normal limits and increased to a mean of 14.4 pg/mL after calcium stimulation. We transformed the peak values before total thyroidectomy to a logarithmic distribution and calculated the normalized mean ± 1.96× standard deviation; the reference upper limit was thus expressed. In the female patients with non-MTC, the reference upper limit was 67.6 pg/mL. In all patients, the calcium stimulation test results after total thyroidectomy showed undetectable basal and stimulated calcitonin values (<0.5 pg/mL). This is the first study to determine reference values to be used for the calcium stimulation test along with an ECLIA in non-MTC patients. We propose that female patients are regarded as biochemically cured or normal when the stimulated calcitonin values by ECLIA are <67.6 pg/mL before surgery and <0.5 pg/mL after total thyroidectomy. PMID:27097651

  2. 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.

  3. Calcitonin gene-related peptide alters the firing rates of hypothalamic temperature sensitive and insensitive neurons

    Directory of Open Access Journals (Sweden)

    Grimm Eleanor R

    2008-07-01

    Full Text Available Abstract Background Transient hyperthermic shifts in body temperature have been linked to the endogenous hormone calcitonin gene-related peptide (CGRP, which can increase sympathetic activation and metabolic heat production. Recent studies have demonstrated that these centrally mediated responses may result from CGRP dependent changes in the activity of thermoregulatory neurons in the preoptic and anterior regions of the hypothalamus (POAH. Results Using a tissue slice preparation, we recorded the single-unit activity of POAH neurons from the adult male rat, in response to temperature and CGRP (10 μM. Based on the slope of firing rate as a function of temperature, neurons were classified as either warm sensitive or temperature insensitive. All warm sensitive neurons responded to CGRP with a significant decrease in firing rate. While CGRP did not alter the firing rates of some temperature insensitive neurons, responsive neurons showed an increase in firing rate. Conclusion With respect to current models of thermoregulatory control, these CGRP dependent changes in firing rate would result in hyperthermia. This suggests that both warm sensitive and temperature insensitive neurons in the POAH may play a role in producing this hyperthermic shift in temperature.

  4. 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.

  5. 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.

  6. 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.

  7. Calcitonin receptor binding in the hen anterior pituitary during an oviposition cycle.

    Science.gov (United States)

    Nakayama, Hiroyuki; Takahashi, Tetsuya; Nakagawa-Mizuyachi, Kaori; Kawashima, Mitsuo

    2011-10-01

    The equilibrium dissociation constant (K(d) ) and the maximum binding capacity (B(max) ) of calcitonin (CT) receptor in the plasma membrane of the anterior pituitary in hens were examined by Scatchard analysis of specific binding of (125) I-labeled chicken CT. Values of K(d) and B(max) of CT receptor were smaller in laying hens than in non-laying hens. A decrease in the K(d) and B(max) value of CT receptor was observed in the anterior pituitary after the injection of estradiol-17β and progesterone into nonlaying hens, but not changed after the injection of 5α-dihydrotestosterone. During an oviposition cycle, the K(d) and the B(max) value decreased 3 h before oviposition. In non-laying hens, neither the K(d) nor the B(max) value changed during a full day period. The present study suggests that the CT action on the anterior pituitary may increase 3 h before oviposition by the effect of estradiol-17β and progesterone in laying hens. PMID:21951904

  8. 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.

  9. GLP-1 and Calcitonin Concentration in Humans: Lack of Evidence of Calcitonin Release from Sequential Screening in over 5000 Subjects with Type 2 Diabetes or Nondiabetic Obese Subjects Treated with the Human GLP-1 Analog, Liraglutide

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Moses, Alan C; Zdravkovic, Milan;

    2011-01-01

    Background: Serum calcitonin (CT) is a well-accepted marker of C-cell proliferation, particularly in medullary thyroid carcinoma. Chronic glucagon-like peptide-1 (GLP-1) receptor agonist administration in rodents has been associated with increased serum CT levels and C-cell tumor formation. There...... are no longitudinal studies measuring CT in humans without medullary thyroid carcinoma or a family history of medullary thyroid carcinoma and no published studies on the effect of GLP-1 receptor agonists on human serum CT concentrations. Aim: The aim of the study was to determine serum CT response...

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

    International Nuclear Information System (INIS)

    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−1 to 7.919 mg L−1 with LOD 3.09 ng L−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−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)

  11. Pharmacologic Characterization of AMG 334, a Potent and Selective Human Monoclonal Antibody against the Calcitonin Gene-Related Peptide Receptor.

    Science.gov (United States)

    Shi, Licheng; Lehto, Sonya G; Zhu, Dawn X D; Sun, Hong; Zhang, Jianhua; Smith, Brian P; Immke, David C; Wild, Kenneth D; Xu, Cen

    2016-01-01

    Therapeutic agents that block the calcitonin gene-related peptide (CGRP) signaling pathway are a highly anticipated and promising new drug class for migraine therapy, especially after reports that small-molecule CGRP-receptor antagonists are efficacious for both acute migraine treatment and migraine prevention. Using XenoMouse technology, we successfully generated AMG 334, a fully human monoclonal antibody against the CGRP receptor. Here we show that AMG 334 competes with [(125)I]-CGRP binding to the human CGRP receptor, with a Ki of 0.02 nM. AMG 334 fully inhibited CGRP-stimulated cAMP production with an IC50 of 2.3 nM in cell-based functional assays (human CGRP receptor) and was 5000-fold more selective for the CGRP receptor than other human calcitonin family receptors, including adrenomedullin, calcitonin, and amylin receptors. The potency of AMG 334 at the cynomolgus monkey (cyno) CGRP receptor was similar to that at the human receptor, with an IC50 of 5.7 nM, but its potency at dog, rabbit, and rat receptors was significantly reduced (>5000-fold). Therefore, in vivo target coverage of AMG 334 was assessed in cynos using the capsaicin-induced increase in dermal blood flow model. AMG 334 dose-dependently prevented capsaicin-induced increases in dermal blood flow on days 2 and 4 postdosing. These results indicate AMG 334 is a potent, selective, full antagonist of the CGRP receptor and show in vivo dose-dependent target coverage in cynos. AMG 334 is currently in clinical development for the prevention of migraine. PMID:26559125

  12. 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.

  13. 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.

  14. 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...

  15. 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...... 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...

  16. Thyroid calcitonin cells in response to glucagon-induced hypocalcaemia in the Indian jackal, Canis aureus (Linnaeus--lex).

    Science.gov (United States)

    Swarup, K; Tewari, N P

    1980-01-01

    Jackal (Canis aureus) puppies (10) were subjected to hypocalcaemia by a single intravenous injection of crystalline porcine glucagon (Eli Lilly and Co.) in a dosage of 0.2 mg/kg body weight. Fasting blood samples from each specimen were collected 30 minutes before injection. Then again after an interval of 15, 30, 60, 90, 120, 150, 180, 210, 240, 270 and 300 minutes blood samples were taken. For histological study animals were killed after 30, 90, 120, 240 and 300 minutes of the injection. The mean serum calcium level records a fall upto 90 minutes but it tends to return to normal and at 300 minutes it returns to the preinjection level. The mean serum inorganic phosphate level records a fall upto 180 minutes and therafter the value increases approaching the preinjection levles after 300 minutes. Specific stains were used for staining the calcitonin cells. Animals killed 30 minutes after the injection exhibit beginning of degranulation of secretory granules in their C cells, while those killed after 300 minutes show marked degranulation. A progressive degranulation of calcitonin cells at the various stages of experimentation displays correspondingly poorer response to the staining reaction. There is no change in the histological picture of the parathyroid. PMID:7424080

  17. 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.

  18. Paradoxical acute hypercalcemic effect of salmon calcitonin in patients having Paget's disease of bone after treatment with dichloromethylene diphosphonate.

    Science.gov (United States)

    Delmas, P D; Chapuy, M C; Meunier, P J

    1984-05-01

    The hypocalcemia following administration of calcitonin may be an index to disease activity in Paget's disease of bone. Therefore, we assessed the effect of a single injection of 100 MRC units of salmon calcitonin (SCT) on plasma calcium in 28 patients with active Paget's disease before and after 6 months of treatment with dichloromethylene diphosphonate (Cl2MDP) at a dose of 400 mg/day (3 patients), 800 mg/day (8 patients), 1.600 mg/day (9 patients) or 2.600 mg/day (8 patients). The mean SCT-induced hypocalcemia was reduced by Cl2MDP and there was a significant positive correlation between the decrease of serum calcium induced by SCT and bone resorption evaluated by the number of osteoclasts on bone biopsy taken in pagetic iliac crest. After Cl2MCP treatment, 5 patients manifested a paradoxical hypercalcemic response to SCT injection ranging from +0.3 mg/dl to +0.5 mg/dl, which was sustained over the 9 hours following injection. As these patients had a dramatic inhibition of bone resorption induced by Cl2 MDP, it is suggested that the hypercalcemic response to SCT might reflect persistence or exaggeration of the early hypercalcemic effect of CT which reportedly precedes the hypocalcemic response to SCT. PMID:6234216

  19. Expression and localization of prohormone convertase PC1 in the calcitonin-producing cells of the bullfrog ultimobranchial gland.

    Science.gov (United States)

    Yaoi, Yuichi; Suzuki, Masakazu; Tomura, Hideaki; Kurabuchi, Shingo; Sasayama, Yuichi; Tanaka, Shigeyasu

    2003-11-01

    We examined the expression and localization of the prohormone convertases, PC1 and PC2, in the ultimobranchial gland of the adult bullfrog using immunohistochemical (IHC) and in situ hybridization (ISH) techniques. In the ultimobranchial gland, PC1-immunoreactive cells were columnar, and were present in the follicular epithelium. When serial sections were immunostained with anti-calcitonin, anti-CGRP, anti-PC1, and anti-PC2 sera, PC1 was found only in the calcitonin/CGRP-producing cells. No PC2-immunopositive cells were detected. In the ISH, PC1 mRNA-positive cells were detected in the follicle cells in the ultimobranchial gland. No PC2 mRNA-positive cells were detected. RT-PCR revealed expression of the mRNAs of PC1 and the PC2 in the ultimobranchial gland. However, very little of the PC2 mRNA is probably translated because no PC2 protein was detected either by IHC staining or by Western blotting analysis. We conclude that the main prohormone convertase that is involved in the proteolytic cleavage of procalcitonin in the bullfrog is PC1. PMID:14566018

  20. 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

    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...

  1. 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.

  2. 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...

  3. 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...

  4. THE CLINICAL IMPLICATIONS OF A POSITIVE CALCITONIN TEST FOR C-CELL HYPERPLASIA IN GENETICALLY UNAFFECTED MEMBERS OF AN MEN2A KINDRED

    NARCIS (Netherlands)

    LANDSVATER, RM; ROMBOUTS, AGM; TEMEERMAN, GJ; SCHILLHORNVANVEEN, JMJ; BERENDS, MJH; GEERDINK, RA; STRUYVENBERG, A; BUYS, CHCM; LIPS, CJM

    1993-01-01

    C-cell hyperplasia precedes the development of medullary thyroid carcinoma in multiple endocrine neoplasia type 2A (MEN2A). Identification of abnormal calcitonin levels after a provocative stimulus is a technique that has been widely used to diagnose this preneoplastic condition in an early stage du

  5. 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.

  6. Controlling N-methyl-D-aspartate receptor subunit 1 with calcitonin gene related peptide after cerebral ischemic injury

    Institute of Scientific and Technical Information of China (English)

    Jixiang Cui; Peng Qu; Chunping Qiao

    2006-01-01

    BACKGROUND: Activation of N-methyl-D-aspartate receptor(NMDAR)is a key link of exitotoxictiy at the phase of cerebral ischemic injury.Because NMDAR is a main way to mediate internal flow of Ca2+ among glutamic acid receptors,over-excitation can cause neuronal apoptosis.Calcitonin gene related peptide has a strongly biological activity.On one hand,it can play the protective effect through inhibiting the expression of NMDAR1 mRNA;on the other hand,it can play the protective effect through down-regulating the expression of NMDAR1 mRNA by exogenous calcitonin gene related peptide.OBJECTIVE: To observe the expression of NMDAR1 and the regulatory effect of calcitonin gene related peptide on the expression of NMDAR1 mRNA and protein in the cerebral cortex of rats with focal cerebral ischemia/reperfusion(I/R).DESIGN: Randomized controlled animal study.SETTING: China Medical University.MATERIALS: A total of 216 healthy male Wistar rats,general grade,weighing 250-280 g,were selected in this study.Twelve rats were randomly selected to regard as control group;meanwhile,other 204 rats were used to establish middle cerebral artery occlusion/reperfusion (MACO)models.The main reagents were detailed as follows:calcitonin gene related peptide (Sigma Company);calcitonin gene related peptide kit (Boster Company);antibodyⅠ,Ⅱand antibody β-actin Ⅰ,Ⅱ of NMDAR1 mRNA and chemiluminescence reagent (Santa Cruz Company,USA)METHODS:The experiment was carried out in the Laboratory of Neurobiology of China Medical University from August 2005 to June 2006. ①Right MCAO models of rats were established to cause focal ischemia and scored based on Zea Longa five-grade scale. If the scores were 1,2 and 3 after wakefulness,the MACO models were established successfully and involved in the experiment. A total of 120 rats with successful modeling were randomly divided into I/R group and administration group with 60 in each group.All rats in the both groups were observed at five time points

  7. Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat

    DEFF Research Database (Denmark)

    Edvinsson, Lars; Eftekhari, Sajedeh; Salvatore, Christopher A;

    2011-01-01

    Clinical and experimental results have revealed a fundamental role of calcitonin gene-related peptide (CGRP) in primary headaches. CGRP is widely expressed in neurons both in the central nervous system (CNS) and in peripheral sensory nerves. In the CNS there is a wide distribution of CGRP...... modifying protein type 1 (RAMP1) have been developed. In the present study we therefore examined immunohistochemically the distribution of CGRP and its receptor components in the cerebellum. CGRP immunoreactivity was only found intracellularly in the cerebellar Purkinje cell bodies, whereas CLR and RAMP1...... were detected on the surface of the Purkinje cell bodies and in their processes. The elaborate dendritic tree of Purkinje cell fibers was distinctly visualized with the RAMP1 antibody. In addition, profoundly stained fibers spanning from the molecular layer into the medulla was observed with the RAMP1...

  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...... potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels....... potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ω-conotoxin GVIA inhibited the potassium induced CGRP release significantly...

  9. 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...... potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels....... potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ¿-conotoxin GVIA inhibited the potassium induced CGRP release significantly...

  10. 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...

  11. 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)

    2001-01-01

    Objective: The current study was designed to investigate the relationship between the pattern of methylation of calcitonin (CT) gene and the activity of DNA methyltranferase (MTase). Methods: The methylation rate of the 5' region of the CT gene (CTMR) and the activity of MTase in 6 solid tumor cell lines and 2 leukemia cell lines were determined. CTMR was detected by polymerase chain reaction (PCR) with inter and external references in combination with restriction endonuclease and laser scan technique. MTase activity was examined by isotope labeled microassay. Results: Both CTMR and MTase activity in all tumor cell lines were significantly higher than that of control cells. The increased MTase activity was relative to elevated CTMR. Conclusion: There is prevalence of hypermethylation of CT gene and elevated activity of MTase in malignant cells. The increased MTase activity is one of the possible reasons for CT gene hypermethylation in tumor cells.

  12. 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

    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...... 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....

  13. Immunohistochemical localization of the calcitonin gene-related peptide binding site in the primate trigeminovascular system using functional antagonist antibodies.

    Science.gov (United States)

    Miller, Silke; Liu, Hantao; Warfvinge, Karin; Shi, Licheng; Dovlatyan, Mary; Xu, Cen; Edvinsson, Lars

    2016-07-22

    Calcitonin gene-related peptide (CGRP) is a potent vasodilator and a neuromodulator implicated in the pathophysiology of migraine. It binds to the extracellular domains of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP) 1 that together form the CGRP receptor. Antagonist antibodies against CGRP and its binding site at the receptor are clinically effective in preventing migraine attacks. The blood-brain barrier penetration of these antagonist antibodies is limited, suggesting that a potential peripheral site of action is sufficient to prevent migraine attacks. To further understand the sites of CGRP-mediated signaling in migraine, we used immunohistochemical staining with recently developed antagonist antibodies specifically recognizing a fusion protein of the extracellular domains of RAMP1 and CLR that comprise the CGRP binding pocket at the CGRP receptor in monkey and man. We confirmed binding of the antagonist antibodies to human vascular smooth muscle cells (VSMCs) of dural meningeal arteries and neurons in the trigeminal ganglion, both of which are likely sites of action for therapeutic antibodies in migraine patients. We further used one of these antibodies for detailed mapping on cynomolgus monkey tissue and found antagonist antibody binding sites at multiple levels in the trigeminovascular system: in the dura mater VSMCs, in neurons and satellite glial cells in the trigeminal ganglion, and in neurons in the spinal trigeminal nucleus caudalis. These data reinforce and clarify our understanding of CGRP receptor localization in a pattern consistent with a role for CGRP receptors in trigeminal sensitization and migraine pathology. PMID:27155150

  14. Organ culture of the trigeminal ganglion induces enhanced expression of calcitonin gene-related peptide via activation of extracellular signal-regulated protein kinase 1/2

    DEFF Research Database (Denmark)

    Tajti, János; Kuris, Anikó; Vécsei, László;

    2011-01-01

    , phosphorylated ERK1/2 (pERK1/2), total ERK1/2 (tERK1/2), phosphorylated p38 (pp38), phosphorylated C-Jun-N-terminal protein kinase (pJNK), pro-calcitonin (pro-CT), CGRP receptor activity modifying protein 1 (RAMP1), glutamine synthetase (GS) and pro-CT were used. To explore molecular mechanisms involved......BACKGROUND AND OBJECTIVE: Clinical and experimental studies have revealed a central role of calcitonin gene-related peptide (CGRP) in primary headaches. The role of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in neuronal and glial cell expression of CGRP- immunoreactivity (-ir) in rat...

  15. Late effect of subtotal thyroidectomy and radioactive iodine therapy on calcitonin secretion and bone mineral density in women treated for Graves' disease

    International Nuclear Information System (INIS)

    This study was designed to evaluate the effect of subtotal thyroidectomy and/or radioactive iodine therapy on plasma immunocalcitonin (iCT) levels and bone densities in patients treated for Graves' disease. Forty-eight women whose ages ranged from 29 to 79 years (mean, 55 years) were evaluated. All were at least 10 years beyond treatment. Fourteen patients had undergone subtotal thyroidectomy, 22 had received radioactive iodine therapy, and 12 had received both. Serum calcitonin levels were measured with the patient fasting and at 30 minutes and 2 hours after the ingestion of 15 mg of calcium in orange juice. Single photon absorptiometry was used to measure bone mineral density of the middle and distal radius. The mean fasting plasma levels of iCT for patients undergoing subtotal thyroidectomy was 27 +/- 2 mumol/L; women treated with radioactive iodine, 26 +/- 2; women undergoing subtotal thyroidectomy followed by radioactive iodine, 24 +/- 2, and for normal control women, 48.5 +/- 4.7. The mean stimulated iCT level of each of the patient groups was significantly lower than that of the normal controls (p = 0.01). There were no significant differences among the groups. Although there was an increased loss of bone mineral density in postmenopausal patients, with age and race as covariates, the bone densities of the distal radius in women undergoing subtotal thyroidectomy and/or receiving radioactive iodine were not significantly lower than those of normal control subjects (p greater than 0.05). These findings are consistent with other observations that patients treated by thyroidectomy and/or radioactive iodine for Graves' disease have lower basal levels of calcitonin and decreased calcitonin response to a provocative stimulus. Whether this loss of calcitonin reserve is a significant factor in development of postmenopausal osteoporosis remains unanswered

  16. Late effect of subtotal thyroidectomy and radioactive iodine therapy on calcitonin secretion and bone mineral density in women treated for Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowery, W.D.; Thomas, C.G. Jr.; Awbrey, B.J.; Rosenstein, B.D.; Talmage, R.V.

    1986-12-01

    This study was designed to evaluate the effect of subtotal thyroidectomy and/or radioactive iodine therapy on plasma immunocalcitonin (iCT) levels and bone densities in patients treated for Graves' disease. Forty-eight women whose ages ranged from 29 to 79 years (mean, 55 years) were evaluated. All were at least 10 years beyond treatment. Fourteen patients had undergone subtotal thyroidectomy, 22 had received radioactive iodine therapy, and 12 had received both. Serum calcitonin levels were measured with the patient fasting and at 30 minutes and 2 hours after the ingestion of 15 mg of calcium in orange juice. Single photon absorptiometry was used to measure bone mineral density of the middle and distal radius. The mean fasting plasma levels of iCT for patients undergoing subtotal thyroidectomy was 27 +/- 2 mumol/L; women treated with radioactive iodine, 26 +/- 2; women undergoing subtotal thyroidectomy followed by radioactive iodine, 24 +/- 2, and for normal control women, 48.5 +/- 4.7. The mean stimulated iCT level of each of the patient groups was significantly lower than that of the normal controls (p = 0.01). There were no significant differences among the groups. Although there was an increased loss of bone mineral density in postmenopausal patients, with age and race as covariates, the bone densities of the distal radius in women undergoing subtotal thyroidectomy and/or receiving radioactive iodine were not significantly lower than those of normal control subjects (p greater than 0.05). These findings are consistent with other observations that patients treated by thyroidectomy and/or radioactive iodine for Graves' disease have lower basal levels of calcitonin and decreased calcitonin response to a provocative stimulus. Whether this loss of calcitonin reserve is a significant factor in development of postmenopausal osteoporosis remains unanswered.

  17. Effect of Tongxinluo Capsule (通心络胶囊) on Plasma Endothelin,Calcitonin Gene-related Peptide and Nitrogen Oxide of Acute Cerebral Infarction Patients

    Institute of Scientific and Technical Information of China (English)

    王宁; 顾锡镇; 邓颖; 张南军; 谈友芬; 蔡新; 王丽珠

    2004-01-01

    @@ Research of TCM shows that the chief pathological basis of acute cerebral infarction (ACI) is "blood stasis obstructing collateral". Here the authors used Tongxinluo capsule (通心络胶囊, TXLC) for replenishing qi, removing stasis and dredging collateral to treat qi deficiency-blood stasis type of ACI, and observed the change of plasma endothelin (ET), calcitonin gene-related peptide (CGRP) and nitrogen oxide (NO), aiming at exploringthe effect of TXLC on vascular endothelial function and neurotransmitter.

  18. Marked depletion of dorsal spinal cord substance P and calcitonin gene-related peptide with intact skin flare responses in multiple system atrophy.

    OpenAIRE

    Anand, P; Bannister, R; McGregor, G P; Ghatei, M A; Mulderry, P K; Bloom, S R

    1988-01-01

    In view of the presence of neuropeptides in spinal cord autonomic pathways, their regional concentration was studied in post mortem thoracic cord from four cases of multiple system atrophy with progressive autonomic failure (MSA). A marked depletion was observed of substance P, its related peptide substance K, and of calcitonin gene-related peptide (CGRP), particularly in dorsal regions where peptide-containing sensory fibres terminate. As substance P and CGRP in primary sensory fibres are co...

  19. Molecular cloning of otoconin-22 complementary deoxyribonucleic acid in the bullfrog endolymphatic sac: effect of calcitonin on otoconin-22 messenger ribonucleic acid levels.

    Science.gov (United States)

    Yaoi, Yuichi; Suzuki, Masakazu; Tomura, Hideaki; Sasayama, Yuichi; Kikuyama, Sakae; Tanaka, Shigeyasu

    2003-08-01

    Anuran amphibians have a special organ called the endolymphatic sac (ELS), containing many calcium carbonate crystals, which is believed to have a calcium storage function. The major protein of aragonitic otoconia, otoconin-22, which is considered to be involved in the formation of calcium carbonate crystals, has been purified from the saccule of the Xenopus inner ear. In this study, we cloned a cDNA encoding otoconin-22 from the cDNA library constructed for the paravertebral lime sac (PVLS) of the bullfrog, Rana catesbeiana, and sequenced it. The bullfrog otoconin-22 encoded a protein consisting of 147 amino acids, including a signal peptide of 20 amino acids. The protein had cysteine residues identical in a number and position to those conserved among the secretory phospholipase A(2) family. The mRNA of bullfrog otoconin-22 was expressed in the ELS, including the PVLS and inner ear. This study also revealed the presence of calcitonin receptor-like protein in the ELS, with the putative seven-transmembrane domains of the G protein-coupled receptors. The ultimobranchialectomy induced a prominent decrease in the otoconin-22 mRNA levels of the bullfrog PVLS. Supplementation of the ultimobranchialectomized bullfrogs with synthetic salmon calcitonin elicited a significant increase in the mRNA levels of the sac. These findings suggest that calcitonin secreted from the ultimobranchial gland, regulates expression of bullfrog otoconin-22 mRNA via calcitonin receptor-like protein on the ELS, thereby stimulating the formation of calcium carbonate crystals in the lumen of the ELS. PMID:12865304

  20. Biological and physical properties of a model calcitonin containing a glutamate residue interrupting the hydrophobic face of the idealized amphiphilic alpha-helical region.

    Science.gov (United States)

    Green, F R; Lynch, B; Kaiser, E T

    1987-01-01

    2A new calcitonin analogue, model calcitonin III (MCt-III), has been synthesized, and its biological and physical characteristics have been studied. This analogue has an idealized alpha-helix from residue 8-22 with glutamate at position 15 interrupting an otherwise continuous surface of aliphatic side chains (those of leucine residues) on the hydrophobic face of the helix. MCt-III differs from a previous model, MCt-II, only by the substitution Leu15----Glu and is here compared with salmon calcitonin I (sCt-I) and MCt-II to elucidate further the role of the putative amphiphilic alpha-helix in determining biological and physical properties of the hormone. MCt-III shows physical properties intermediate between those of sCt-I and MCt-II, demonstrating the influence of appropriately positioned single residues on properties of amphiphilic structures. In our two biological assays, a brain-binding assay and an in vivo hypocalcemic assay, MCt-III reproduces the sigmoidal dose-response curves of sCt-I; this contrasts with the behavior of MCt-II, which demonstrated unusual dose-response curves in these two assays. MCt-III is almost three times more potent than sCt-I in our hypocalcemic assay; this activity groups MCt-III among the most potent known analogues of sCt-I. PMID:2825187

  1. 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.

  2. 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.

  3. 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.

  4. Calcitonin gene-related peptide immunoreactive sensory neurons in the vagal and glossopharyngeal ganglia innervating the larynx of the rat.

    Science.gov (United States)

    Hayakawa, Tetsu; Kuwahara-Otani, Sachi; Maeda, Seishi; Tanaka, Koichi; Seki, Makoto

    2014-01-01

    We have examined whether calcitonin gene-related peptide-immunoreactive (CGRP-ir) neurons in the vagal and glossopharyngeal ganglia innervate the larynx. Many CGRP-ir neurons were located mostly in the superior glossopharyngeal-jugular ganglion complex that was fused the superior glossopharyngeal ganglion and the jugular ganglion in the cranial cavity. When Fluorogold was applied to the cut end of the superior laryngeal nerve (SLN) or the recurrent laryngeal nerve (RLN), many Fluorogold-labeled neurons were found in the superior glossopharyngeal-jugular ganglion complex and the nodose ganglion. Double-labeling for CGRP and Fluorogold showed that about 80% of Fluorogold-labeled neurons in the superior glossopharyngeal-jugular ganglion complex expressed CGRP-like immunoreactivity in the case of application to the SLN, and about 50% of Fluorogold-labeled neurons expressed CGRP-like immunoreactivity in the case of the RLN. Only a few double-labeled neurons were found in the nodose ganglion. The number of the Fluorogold-labeled neurons and double-labeled neurons in the superior glossopharyngeal-jugular ganglion complex in the case of the SLN was larger than that in the case of the RLN. These results indicate that sensory information from the larynx might be conveyed by many CGRP-ir neurons located in the superior glossopharyngeal-jugular ganglion complex by way of the SLN and the RLN. PMID:24269509

  5. 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.

  6. 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.

  7. Autoradiographic localization of calcitonin gene-related peptide (CGRP) binding sites in human and guinea pig lung

    International Nuclear Information System (INIS)

    125I-Human calcitonin gene-related peptide (hCGRP) binding sites were localized in human and guinea pig lungs by an autoradiographic method. Scatchard analysis of saturation experiments from slide-mounted sections of guinea pig lung displayed specific 125I-hCGRP binding sites with a dissociation constant (Kd) of 0.72 +/- 0.05 nM (mean +/- S.E.M., n = 3) and a maximal number of binding sites (Bmax) of 133.4 +/- 5.6 fmol/mg protein. In both human and guinea pig lung, autoradiography revealed that CGRP binding sites were widely distributed, with particularly dense labeling over bronchial and pulmonary blood vessels of all sizes and alveolar walls. Airway smooth muscle and epithelium of large airways was sparsely labeled but no labeling was found over submucosal glands. This localization corresponds well to the reported pattern of CGRP-like immunoreactive innervation. The findings of localization of CGRP binding sites on bronchial and pulmonary blood vessels indicate that CGRP may be important in the regulation of airway and pulmonary blood flow

  8. The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies

    Directory of Open Access Journals (Sweden)

    Galit Fichman

    2014-08-01

    Full Text Available Amyloid deposits are insoluble fibrous protein aggregates, identified in numerous diseases, which self-assemble through molecular recognition. This process is facilitated by short amino acid sequences, identified as minimal modules. Peptides corresponding to these motifs can be used for the formation of amyloid-like fibrillar assemblies in vitro. Such assemblies hold broad appeal in nanobiotechnology due to their ordered structure and to their ability to be functionalized. The catechol functional group, present in the non-coded L-3,4-dihydroxyphenylalanine (DOPA amino acid, can take part in diverse chemical interactions. Moreover, DOPA-incorporated polymers have demonstrated adhesive properties and redox activity. In this work, amyloid-like fibrillar assemblies were formed through the self-assembly of a pentapeptide containing DOPA residues, Asp-DOPA-Asn-Lys-DOPA. The design of this peptide was based on the minimal amyloidogenic recognition motif of the human calcitonin hormone, Asp-Phe-Asn-Lys-Phe, the first amyloidogenic pentapeptide identified. By substituting phenylalanine with DOPA, we obtained DOPA-functionalized amyloid-like assemblies in water. Electron microscopy revealed elongated, linear fibril-like nanometric assemblies. Secondary structure analysis indicated the presence of amyloid-characteristic β-sheet structures as well as random coil structures. Deposition of silver on the DOPA-incorporated assemblies suggested redox activity and demonstrated the applicative potential of this novel nanobiomaterial.

  9. Synthetic human calcitonin: Analysis of antibodies obtained from various animal species and determination of immunoreactive hormone in human sera

    International Nuclear Information System (INIS)

    Antibodies to synthetic human calcitonin (hCT) were developed in rabbits, goats and mice. The free peptide (32 amino-acid residues, Mwt. 3418) was administered together with adjuvant, and the effect of various immunization procedures, as well as of different dose-levels, was evaluated comparatively. Synthetic hCT was found to be a good immunogen for the three animal species examined. The relative importance of various structural parts of the hCT molecule with regard to immunological specificity was determined by reference to the inhibition of the specific binding of 125I-hCT to antibodies by peptide fragments of hCT. All the antisera studied were directed to structural and/or conformational properties of the 11-28 or 11-32 amino acid sequence of hCT. Six different antisera from rabbits and goats were selected for radioimmunological assay of hCT on the basis of their inhibitory dose50-values and immunological specificity. To improve the sensitivity of the radioimmunoassay (RIA), we studied the preparation of radioiodinated hCT and assessed various parameters determining the sensitivity of the assay. Despite all the efforts, CT in human plasma from healthy subjects could not be determined with certainty. The difficulties encountered in the regard to immunological speciticity. Antibodies exhibiting different immunological properties were then selected for the determination of CT in human sera. (author)

  10. 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.

  11. Nitric oxide synthase inhibitors can antagonize neurogenic and calcitonin gene-related peptide induced dilation of dural meningeal vessels

    Science.gov (United States)

    Akerman, S; Williamson, D J; Kaube, H; Goadsby, P J

    2002-01-01

    The detailed pathophysiology of migraine is beginning to be understood and is likely to involve activation of trigeminovascular afferents. Clinically effective anti-migraine compounds are believed to have actions that include peripheral inhibition of calcitonin gene-related peptide (CGRP) release from trigeminal neurones, or preventing dural vessel dilation, or both. CGRP antagonists can block both neurogenic and CGRP-induced dural vessel dilation. Nitric oxide (NO) can induce headache in migraine patients and often triggers a delayed migraine. The initial headache is thought to be caused via a direct action of the NO–cGMP pathway that causes vasodilation by vascular smooth muscle relaxation, while the delayed headache is likely to be a result of triggering trigeminovascular activation. Nitric oxide synthase (NOS) inhibitors are effective in the treatment of acute migraine. The present studies used intravital microscopy to examine the effects of specific NOS inhibitors on neurogenic dural vasodilation (NDV) and CGRP-induced dilation. The non-specific and neuronal NOS (nNOS) inhibitors were able to partially inhibit NDV, while the non-specific and endothelial NOS (eNOS) inhibitors were able to partially inhibit the CGRP induced dilation. There was no effect of the inducible NOS (iNOS) inhibitor. The data suggest that the delayed headache response triggered by NO donors in humans may be due, in part, to increased nNOS activity in the trigeminal system that causes CGRP release and dural vessel dilation. Further, eNOS activity in the endothelium causes NO production and smooth muscle relaxation by direct activation of the NO–cGMP pathway, and may be involved in the initial headache response. PMID:12183331

  12. 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. PMID:27480451

  13. Osteogenic potential of human calcitonin gene-related peptide alpha gene-modified bone marrow mesenchymal stem cells

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-sheng; WANG Ya-han; ZHAO Guo-qiang; LI Yue-bai

    2011-01-01

    Background Most of the basic and clinical studies of osteonecrosis of the femoral head (ONFH) are restricted to bone tissues only,whereas various systems are involved in the onset and development of ONFH,including nervous system.Peptidergic nerve participates in the neuronal regulation of bone metabolism and anabolism,and plays key roles in the growth,repair and reconstruction of bone.Calcitonin gene-related peptide (CGRP),which is secreted by peptidergic nerve,is the main mediator of bone metabolism.It dramatically promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).Additionally,it enhances the osteoblast mass and the rate of osteoblast formation,and reduces the bone resorption by acting on osteoblasts and osteoclasts.Hence,we aimed to construct recombinant retrovirus vector pLNCX2-hCGRPα and to investigate the proliferation and osteogenic potential of hCGRPα-producing BMSCs (BMSCs/pLNCX2-hCGRPα) after virus infection.Methods The constructed recombinant retrovirus vector pLNCX2-hCGRPα was transfected into PT67 packaging cells by lipofectamine 2000.Virus was collected for BMSCs infection.The mRNA and protein expression of hCGRPα was examined by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting,respectively.The cell proliferation was determined by methyl thiazoleterazolium (MTT) assay.The osteogenic potential of BMSCs was evaluated by alkaline phosphatase (ALP) activity.Results Both mRNA and protein expression of hCGRPα was detected in BMSCs/pLNCX2-hCGRPα cells.These cells exhibited significantly elevated proliferation and ALP value as compared with control BMSCs (P <0.05).Conclusion BMSCs/pLNCX2-hCGRPα cells could stably express hCGRPα and showed promoted proliferation ability and osteogenic potential as compared with control BMSCs.

  14. Expression of calcitonin gene-related peptide in efferent vestibular system and vestibular nucleus in rats with motion sickness.

    Directory of Open Access Journals (Sweden)

    Wang Xiaocheng

    Full Text Available UNLABELLED: Motion sickness presents a challenge due to its high incidence and unknown pathogenesis although it is a known fact that a functioning vestibular system is essential for the perception of motion sickness. Recent studies show that the efferent vestibular neurons contain calcitonin gene-related peptide (CGRP. It is a possibility that the CGRP immunoreactivity (CGRPi fibers of the efferent vestibular system modulate primary afferent input into the central nervous system; thus, making it likely that CGRP plays a key role in motion sickness. To elucidate the relationship between motion sickness and CGRP, the effects of CGRP on the vestibular efferent nucleus and the vestibular nucleus were investigated in rats with motion sickness. METHODS: An animal model of motion sickness was created by subjecting rats to rotary stimulation for 30 minutes via a trapezoidal stimulation pattern. The number of CGRPi neurons in the vestibular efferent nucleus at the level of the facial nerve genu and the expression level of CGRPi in the vestibular nucleus of rats were measured. Using the ABC method of immunohistochemistry technique, measurements were taken before and after rotary stimulation. The effects of anisodamine on the expression of CGRP in the vestibular efferent nucleus and the vestibular nucleus of rats with motion sickness were also investigated. RESULTS AND DISCUSSION: Both the number of CGRPi neurons in the vestibular efferent nucleus and expression level in the vestibular nucleus increased significantly in rats with motion sickness compared to that of controls. The increase of CGRP expression in rats subjected to rotary stimulation 3 times was greater than those having only one-time stimulation. Administration of anisodamine decreased the expression of CGRP within the vestibular efferent nucleus and the vestibular nucleus in rats subjected to rotary stimulation. In conclusion, CGRP possibly plays a role in motion sickness and its mechanism

  15. Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP)

    OpenAIRE

    Marcin Magierowski; Katarzyna Jasnos; Zbigniew Sliwowski; Marcin Surmiak; Gracjana Krzysiek-Maczka; Agata Ptak-Belowska; Slawomir Kwiecien; Tomasz Brzozowski

    2014-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farn...

  16. 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...

  17. Changes in plasma calcitonin gene-related peptide and serum neuron specific enolase in rats with acute cerebral ischemia after low-frequency electrical stimulation with different waveforms and intensities

    Institute of Scientific and Technical Information of China (English)

    Qiang Gao; Yonghong Yang; Shasha Li; Jing He; Chengqi He

    2011-01-01

    Following acute cerebral ischemia in rats, plasma calcitonin gene-related peptide decreased and the level of serum neuron specific enolase and the volume of the infarction increased. Square-wave and triangular-wave electrical stimulation with low or high intensities could increase the plasma calcitonin gene-related peptide, decrease the serum neuron specific enolase and reduce the infarction volume in the brain in rats with cerebral ischemia. There was no significant difference between different wave forms and intensities. The experimental findings indicate that low-frequency electrical stimulation with varying waveforms and intensities can treat acute cerebral ischemia in rats.

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

    Science.gov (United States)

    Sinsuebpol, Chutima; Chatchawalsaisin, Jittima; Kulvanich, Poj

    2013-01-01

    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 prepared to have appropriate aerodynamic properties for pulmonary delivery. The developed system was able to deliver sCT via a pulmonary route into the systemic circulation. PMID:24039397

  19. Calcitonin blood test

    Science.gov (United States)

    ... than-normal level may indicate: Insulinoma Lung cancer Medullary cancer of thyroid (most common) VIPoma Higher-than-normal levels can also occur in people with kidney disease, smokers, higher body weight, and when taking certain ...

  20. 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.

  1. 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...... 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........c. administrations for 56 days, and glucose tolerance was assessed after one acute injection, 3 weeks of treatment, and again after 7 weeks of treatment. To assess the effect on insulin sensitivity, rats received 5 μg/kg KBP-042 for 21 days before hyperinsulinemic-euglycemic clamp. Results: KBP-042 induced a...

  2. 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

    BACKGROUND AND AIM: 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) systems on the GTN-induced neuronal activation in this model. MATERIALS AND METHODS: The femoral vein was catheterised in rats and GTN was infused (4 µg/kg/min, for 20 minutes, intravenously). Immunohistochemistry was performed to analyse Fos, nNOS and CGRP and Western blot for measuring n......NOS protein expression. The effect of olcegepant, L-nitro-arginine methyl ester (L-NAME) and neurokinin (NK)-1 receptor antagonist L-733060 were analysed on Fos activation. RESULTS: GTN-treated rats showed a significant increase of nNOS and CGRP in dura mater and CGRP in the trigeminal nucleus caudalis (TNC...

  3. Diverse Physiological Roles of Calcitonin Gene-Related Peptide in Migraine Pathology: Modulation of Neuronal-Glial-Immune Cells to Promote Peripheral and Central Sensitization.

    Science.gov (United States)

    Durham, Paul L

    2016-08-01

    The neuropeptide calcitonin gene-related peptide (CGRP) is implicated in the underlying pathology of migraine by promoting the development of a sensitized state of primary and secondary nociceptive neurons. The ability of CGRP to initiate and maintain peripheral and central sensitization is mediated by modulation of neuronal, glial, and immune cells in the trigeminal nociceptive signaling pathway. There is accumulating evidence to support a key role of CGRP in promoting cross excitation within the trigeminal ganglion that may help to explain the high co-morbidity of migraine with rhinosinusitis and temporomandibular joint disorder. In addition, there is emerging evidence that CGRP facilitates and sustains a hyperresponsive neuronal state in migraineurs mediated by reported risk factors such as stress and anxiety. In this review, the significant role of CGRP as a modulator of the trigeminal system will be discussed to provide a better understanding of the underlying pathology associated with the migraine phenotype. PMID:27334137

  4. Long-lasting physiological antagonism of calcitonin gene-related peptide towards endothelin-1 in rat mesenteric arteries and human coronary arteries

    DEFF Research Database (Denmark)

    Labruijere, Sieneke; Compeer, Matthijs G; van den Bogaerdt, Antoon J;

    2013-01-01

    calcitonin-gene related peptide (CGRP), most likely because CGRP causes ET-1/ETAR dissociation. Here we investigated this phenomenon in human coronary microarteries (HCMA). We simultaneously verified the effects of CGRP in RMA and HCMA towards other vasoconstrictors, i.e., the α1-adrenoceptor agonist...... on top of ET-1-initiated contraction in RMA, CGRP effectively counteracted vasoconstriction, i.e., it caused full relaxation. Inhibitory effects of CGRP were also observed when briefly exposing RMA and HCMA to CGRP 1h before the addition of ET-1. Similar inhibitory effects of transient CGRP pre......-incubation were seen towards phenylephrine, U46619 or KCl in RMA and HCMA. In conclusion, our data imply that CGRP, like ET-1, causes long-lasting effects that remain apparent up to 1h after its removal from the organ bath. Thus, in addition to the reported dissociation of ET-1/ETAR complexes, CGRP causes long...

  5. 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...

  6. 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.

  7. 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

  8. 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

  9. Recombinant human calcitonin in myoblasts promotes the proliferation and differentitation of rat osteoblasts%重组成肌细胞合成人降钙素促进大鼠成骨细菌细胞增殖和分化

    Institute of Scientific and Technical Information of China (English)

    王烨明; 曾炳芳; 李晓林

    2007-01-01

    背景:大剂量多次喷鼻或者肌注降钙素能有效地预防绝经后妇女脊柱骨的丟失.但是降钙素需要长时期反复用药、价格昂贵、且有弱的抗原性,限制了长期使用.基因治疗可以为骨质疏松症提供更加有效、经济的治疗方案,同时减少药物的副作用.目的:观察人降钙素基因在成肌细胞中的表达,分析重组人降钙素对体外大鼠成骨细胞的影响.设计:以基因为实验对象,对比观察实验.单位:复旦大学放射医学研究所.材料:实验于2005-12/2006-06在复旦大学放射医学研究所完成.选用健康SD胎鼠10只,由复旦大学放射医学研究所提供.人降钙素单克隆抗体购于美国santa Cruz生物技术公司.L6成肌细胞由中国科学院上海生命科学研究院生物化学与细胞生物学研究所提供.方法:在L6成肌细胞培养基中分别加入pcDNA3.0-hCT脂质体转染混合物(转染组)和空载体pcDNA3.0脂质体混合物(对照组)进行培养.采用ELISA法、Westem Blot和免疫组织化学鉴定目的基因的蛋白表达.在成骨细胞培养基中分别加入1×10-14,1×10-13,1×10-12mol/L重组人降钙素和MEM.主要观察指标:利用MTT和检测碱性磷酸酶活性的方法观察大鼠成骨细胞增殖和分化的变化.结果:EUSA法可在细胞培养液中检测到降钙素蛋白;Western blot及免疫组化均证实人降钙素在转染后的成肌细胞中获得稳定表达.当重组人降钙素的浓度为1×10-14,1×10-13 mol/L时成骨细胞活性和成骨细胞碱性磷酸酶活性较对照组增高,但差异无显著性意义(P>0.05);浓度升高为1×10-12 mol/L时,明显高于对照组(P<0.05).结论:借助基因转染的方法,成肌细胞可以稳定合成、分泌人降钙素.重组人降钙素有促进骨形成的作用.%BACKGROUND:Repeated injections or nasal spray of large doses of calcitonin can effectively prevent postmenopausal osteoporosis. Calcitonin should be taken for a long time

  10. 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.

  11. Calcitonin gene-related peptide inhibits interleukin-1β-induced interleukin-8 secretion in human type Ⅱ alveolar epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Wen-jing LI; Teng-ke WANG; Xian WANG

    2006-01-01

    Aim: Our previous data have shown that type Ⅱ alveolar epithelial (AEII) cells express neuropeptide calcitonin gene-related peptide (CGRP), and that pro-inflammatory factor interleukinl-β(IL-1β) induces CGRP secretion in the A549 human AEII cell line. In the present study, we investigated the effect of endogenous and exogenous CGRP on IL-1β-induced chemokine interleukin-8 (IL-8) secretion. Methods: We used enzyme-linked immunosorbent assay (ELISA) and RT-PCR to detect IL-8 protein and mRNA levels, respectively. siRNA and the stably transfected cell line were used to knock down and overexpress the CGRP gene, respectively, and chemiluminescence assay was used to detect reactive oxygen species (ROS) formation. Results: CGRP-1 receptor antagonist hCGRP8-37 (0.1-1 nmol·L-1) greatly amplified IL-1β-induced IL-8 production. The inhibition of CGRP expression by siRNA significantly increased IL-8 secretion upon IL-1β stimulation. However, cell clones stably transfected with CGRP showed significantly inhibited mRNA and protein levels of IL-8 induced by IL-1β. Conclusion: These data imply that AEII cell-derived CGRP suppress EL-1β-induced IL-8 secretion in an autocrine/paracrine mode. Further investigation showed that CGRP attenuated IL-1β-aroused ROS formation, which is an early indication of pro-inflammatory factor signaling.

  12. Calcitonin gene-related peptide is a key factor in the homing of transplanted human MSCs to sites of spinal cord injury.

    Science.gov (United States)

    Zhang, Yu; Yang, Jinhua; Zhang, Peng; Liu, Tao; Xu, Jianwei; Fan, Zhihai; Shen, Yixin; Li, Wenjie; Zhang, Huanxiang

    2016-01-01

    Mesenchymal stem cells (MSCs) can be used to treat many diseases, including spinal cord injury (SCI). Treatment relies mostly on the precise navigation of cells to the injury site for rebuilding the damaged spinal cord. However, the key factors guiding MSCs to the epicenter of SCI remain unknown. Here, we demonstrated that calcitonin gene-related peptide (CGRP), a neural peptide synthesized in spinal cord, can dramatically aid the homing of human umbilical cord mesenchymal stem cells (HUMSCs) in spinal cord-transected SCI rats. First, HUMSCs exhibited chemotactic responses in vitro to CGRP. By time-lapse video analysis, increased chemotactic index (CMI), forward migration index (FMI) and speed contributed to this observed migration. Then, through enzyme immunoassay, higher CGRP concentrations at the lesion site were observed after injury. The release of CGRP directed HUMSCs to the injury site, which was suppressed by CGRP 8-37, a CGRP antagonist. We also verified that the PI3K/Akt and p38MAPK signaling pathways played a critical role in the CGRP-induced chemotactic migration of HUMSCs. Collectively, our data reveal that CGRP is a key chemokine that helps HUMSCs migrate to the lesion site and thereby can be used as a model molecule to study MSCs homing after SCI. PMID:27296555

  13. 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.

  14. 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). PMID:27279064

  15. 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.

  16. 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

    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< 0.05) and inversely related to plasma adrenaline levels (r=-0.......53; p<0.02) but positively related to circulating levels of CGRP (r=0.58; p<0.01). No significant relation was found for plasma noradrenaline, renin activity, or endothelin-1. COMP(art) was positively related to plasma volume (r=0.50; p<0.02) and inversely to systemic vascular resistance (r=-0.69; p<0.......001) and central circulation time (r=-0.49; p<0.02). During oxygen inhalation, COMP(art) decreased (-13%; p<0.005) and systemic vascular resistance increased (+10%; p<0.001) towards normal values without significant changes in mean arterial pressure. Plasma adrenaline (-16%; p<0.01) decreased and the...

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

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    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

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

    Directory of Open Access Journals (Sweden)

    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

  19. 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.

  20. Exogenous Asymmetric Dimethylarginine (ADMA in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO and Calcitonin Gene-Related Peptide (CGRP

    Directory of Open Access Journals (Sweden)

    Marcin Magierowski

    2014-03-01

    Full Text Available Asymmetric dimethylarginine (ADMA is an endogenous nitric oxide (NO synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I and 3 h of reperfusion (R. These I/R animals were pretreated with ADMA with or without the combination of l-arginine, calcitonin gene-related peptide (CGRP or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, l-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties.

  1. Exogenous asymmetric dimethylarginine (ADMA) in pathogenesis of ischemia-reperfusion-induced gastric lesions: interaction with protective nitric oxide (NO) and calcitonin gene-related peptide (CGRP).

    Science.gov (United States)

    Magierowski, Marcin; Jasnos, Katarzyna; Sliwowski, Zbigniew; Surmiak, Marcin; Krzysiek-Maczka, Gracjana; Ptak-Belowska, Agata; Kwiecien, Slawomir; Brzozowski, Tomasz

    2014-01-01

    Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthesis inhibitor and pro-inflammatory factor. We investigated the role of ADMA in rat gastric mucosa compromised through 30 min of gastric ischemia (I) and 3 h of reperfusion (R). These I/R animals were pretreated with ADMA with or without the combination of L-arginine, calcitonin gene-related peptide (CGRP) or a small dose of capsaicin, all of which are known to afford protection against gastric lesions, or with a farnesoid X receptor (FXR) agonist, GW 4064, to increase the metabolism of ADMA. In the second series, ADMA was administered to capsaicin-denervated rats. The area of gastric damage was measured with planimetry, gastric blood flow (GBF) was determined by H2-gas clearance, and plasma ADMA and CGRP levels were determined using ELISA and RIA. ADMA significantly increased I/R-induced gastric injury while significantly decreasing GBF, the luminal NO content, and the plasma level of CGRP. This effect of ADMA was significantly attenuated by pretreatment with CGRP, L-arginine, capsaicin, or a PGE2 analogue. In GW4064 pretreated animals, the I/R injury was significantly reduced and this effect was abolished by co-treatment with ADMA. I/R damage potentiated by ADMA was exacerbated in capsaicin-denervated animals with a further reduction of CGRP. Plasma levels of IL-10 were significantly decreased while malonylodialdehyde (MDA) and plasma TNF-α contents were significantly increased by ADMA. In conclusion, ADMA aggravates I/R-induced gastric lesions due to a decrease of GBF, which is mediated by a fall in NO and CGRP release, and the enhancement of lipid peroxidation and its pro-inflammatory properties. PMID:24658439

  2. 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

  3. 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.

  4. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

    International Nuclear Information System (INIS)

    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [125I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser449 to Ser467 were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

  5. The development of a human calcitonin radioimunoassay, with 'in house' reagent production, for application to the early diagnosis of medullary thyroid carcioma

    International Nuclear Information System (INIS)

    Reagent production for human Calcitonin (hCT) Radioimmunoassay (RIA) was carried out in our laboratory starting from a kind donation of human synthetic preparation from CIBA (Basel, Switzerland). This product was used for anti-hCT antibody production in rabbits and guinea-pigs and for radioiodination, according to two different methods: classical and stoichiometric Chloramine T techniques. The use of Sephadex G-50 in tracer purification allowed the obtainement of 125I-hCT free of high molecular weight contaminats. A repurification on polyacrylamide gel electrophoresis provided 125I-hCT of higher specific activity that presented specific binginds, to good quality antisera, of the same order of imported tracers (∼ 45%). Different antisera were obtained in rabbits and quinea-pigs, but only one (GP2-IPEN) could be used in such a dilution (1:4000) to provide highly sensitive curves (minimal detectable concentration < 70 pg/ml) presenting, however, very low specific bindings (7-10%). For this reason, in order to be able to set up a regular quality control of our hCT-RIA technique, an antiserum kindly donated by the Karolinska Institute (Stockholm, Sweden) was used. This way, through the use of an higher antibody dilution (1:8000), higher specific bindings (20-30%), higher sensitivies (< 30 pg/ml) and satisfactory precision were obtained. We consider this study a first approach to a complete national production of hCT-RIA reagents, that, at present moment, depends practically only from the obtainement of a high avidity anti-hCT antiserum. More has to be done on accuracy and correct clinical application of this assay to the screening of the familial form of Medullary Thyroid Carcinoma. We also emphasize the fact, due to our limited financial possibilities, all the work was carried out with great economy, taking advantage of previously set up techniques and of the experience already acquired in this field of work. (author)

  6. 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

  7. Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Kuwasako, Kenji, E-mail: kuwasako@fc.miyazaki-u.ac.jp [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kitamura, Kazuo; Nagata, Sayaka; Hikosaka, Tomomi [Division of Circulation and Body Fluid Regulation, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan); Kato, Johji [Frontier Science Research Center, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2010-02-12

    Receptor activity-modifying protein 2 (RAMP2) enables calcitonin receptor-like receptor (CRLR) to form an adrenomedullin (AM)-specific receptor. Here we investigated the function of the cytoplasmic C-terminal tail (C-tail) of human (h)CRLR by co-transfecting its C-terminal mutants into HEK-293 cells stably expressing hRAMP2. Deleting the C-tail from CRLR disrupted AM-evoked cAMP production or receptor internalization, but did not affect [{sup 125}I]AM binding. We found that CRLR residues 428-439 are required for AM-evoked cAMP production, though deleting this region had little effect on receptor internalization. Moreover, pretreatment with pertussis toxin (100 ng/mL) led to significant increases in AM-induced cAMP production via wild-type CRLR/RAMP2 complexes. This effect was canceled by deleting CRLR residues 454-457, suggesting Gi couples to this region. Flow cytometric analysis revealed that CRLR truncation mutants lacking residues in the Ser/Thr-rich region extending from Ser{sup 449} to Ser{sup 467} were unable to undergo AM-induced receptor internalization and, in contrast to the effect on wild-type CRLR, overexpression of GPCR kinases-2, -3 and -4 failed to promote internalization of CRLR mutants lacking residues 449-467. Thus, the hCRLR C-tail is crucial for AM-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.

  8. Anti-inflammatory role of methotrexate in adjuvant arthritis: effect on substance p and calcitonin gene-related peptide in thymus and spleen

    International Nuclear Information System (INIS)

    To investigate the anti-inflammatory effect of methotrexate (MTX) in rats with adjuvant arthritis through its influence on the expression of proinflammatory neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP) in immune organs, thymus and spleen. Adjuvant arthritis was induced in rats by inoculation with heat-killed mycobacteria. One group of arthritic rats (n=6) was treated with MTX (0.2 mg/kg body weight, subcutaneously) on every 4th day for a period of 18 weeks, while another group of arthritic rats (n=6) was treated with physiological saline served as control. At the end of experiment, animals were sacrificed and thymus and spleen were dissected and prepared for immunohistochemical analysis. The neuronal density of SP and CGRP immunoreactivity in thymus and spleen was assessed by semi-quantitative analysis. There was a marked reduction in hind paw swelling and inflammation in the MTX-treated rats after 18 weeks of treatment. Restoration of joint spaces (tibiotalar and subtalar) was seen after 9 weeks of MTX treatment. CGRP-positive nerve fibres were significantly reduced (p=0.0001) in thymus of rats treated with MTX compared to control rats. SP-positive nerve fibers were also found to be decreased in thymus of rats treated with MTX compared to controls, however, the decrease was not statistically significant. The neuronal density of SP and CGRP-immunoreactivity in spleen was not significantly different in MTX-treated and placebo-treated rats. In arthritic rats, MTX significantly reduced CGRP expression in thymus. Suppression of pro-inflammatory neuropeptides, such as CGRP and probably SP could be another mechanism by which MTX produces its antiinflammatory effect in adjuvant arthritis. (author)

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Calcitonin gene-related peptide induces proliferation and monocyte chemoattractant protein-1 expression via extracellular signal-regulated kinase activation in rat osteoblasts

    Institute of Scientific and Technical Information of China (English)

    HAN Na; ZHANG Dian-ying; WANG Tian-bing; ZHANG Pei-xun; JIANG Bao-guo

    2010-01-01

    Background Calcitonin gene-related peptide (CGRP), a sensory neuropeptide, affects osteoblast proliferation and bone formation. However, the mechanisms are not fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine that stimulates the migration of monocytes and plays important roles in regulating bone remolding during fracture repair, In this study, we investigated the effects of CGRP on proliferation and MCP-1 expression in cultured rat osteoblasts.Methods Primary rat osteoblasts were isolated from fetal rats calvariae. Cells were exposed to gradient concentrations (10-9 to 10-7 mol/L) of CGRP. Protein and mRNA levels of MCP-1 were quantified by Western blotting and semiquantitative reverse transcription-polymerase chain reaction, respectively. The protein level of MCP-1 was investigated and compared in cell culture media by enzyme linked immunosorbent assay (ELISA). Phospho-extracellular signal-regulated kinase (ERK) expression was detected by Western blotting. Cell proliferative activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and BrdU assay. The effects of MAPK/ERK kinase (MEK)-inhibitor U0126 on CGRP-induced MCP-1 expression in primary rat osteoblasts were examined.Results CGRP effectively enhanced primary rat osteoblast proliferation and led to significant increases in the expression of MCP-1 mRNA and protein in time- and dose-dependent manners. CGRP activated the ERK pathway.Pretreatment of cultured rat osteoblasts with MEK inhibitor U0126 resulted in dose-dependent inhibitions of CGRP-induced MCP-1 mRNA and protein levels. Thus, CGRP promoted cell proliferation and stimulated MCP-1 expression in cultured rat osteoblasts.Conclusion These studies document novel links between CGRP and MCP-1 and illuminate the effects of CGRP in regulating bone remodeling.

  11. 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.

  12. Cervical lymph node metastases from thyroid cancer: does thyroglobulin and calcitonin measurement in fine needle aspirates improve the diagnostic value of cytology?

    Directory of Open Access Journals (Sweden)

    Baldini Enke

    2013-02-01

    Full Text Available Abstract Background Measurement of thyroglobulin (Tg protein in the washout of the needle used for fine needle aspiration biopsy cytology (FNAB-C has been shown to increase the sensitivity of FNAB-C in identifying cervical lymph node (CLN metastasis from well-differentiated thyroid cancer (TC. In this study, we evaluated whether routine measurement of Tg protein (FNAB-Tgp, Tg mRNA (FNAB-Tgm and calcitonin (CT mRNA (FNAB-CTm in the FNAB washout of CLN increases the accuracy of FNAB-C in the diagnosis of suspicious metastatic CLN. Methods In this prospective study 35 CLN from 28 patients were examined. Histology showed metastatic papillary TC (PTC in 26 CLN, metastatic medullary TC (MTC in 3 CLN, metastatic anaplastic TC (ATC in 3 CLN and 3 metastatic CLN from extra-thyroidal cancers. Results The overall accuracy of FNAB-C was 84.4%, reaching 95.7% when the analysis was restricted to PTC. Both FNAB-Tgp and FNAB-Tgm compared favorably with FNAB-C and shown diagnostic performances not statistically different from that of FNAB-C. However, FNAB-Tgp and FNAB-Tgm/FNAB-CTm were found useful in cases in which cytology results were inadequate or provided diagnosis inconsistent with patient's clinical parameters. Conclusions We demonstrated that FNAB-C, Tg/CT mRNA and Tg protein determination in the fine-needle washout showed similar accuracy in the diagnosis of metastatic CLN from TC. The results of this study suggest that samples for Tg protein and Tg/CT mRNA measurements from CLN suspicious for metastatic TC should be collected, but their measurements should be restricted to cases in which FNAB-C provides uninformative or inconsistent diagnosis with respect to patient's clinical parameters.

  13. 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。

  14. 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. PMID:26349051

  15. 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

  16. 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

  17. 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.

  18. 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. PMID:25447822

  19. 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

  20. A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D.

    Science.gov (United States)

    Henriksen, Kim; Byrjalsen, Inger; Andersen, Jeppe R; Bihlet, Asger R; Russo, Luis A; Alexandersen, Peter; Valter, Ivo; Qvist, Per; Lau, Edith; Riis, Bente J; Christiansen, Claus; Karsdal, Morten A

    2016-10-01

    This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D plus either SMC021 tablets (0.8mg/d) or placebo for 36months. The primary endpoint was the proportion of patients with a new vertebral fracture. The two groups were well balanced at baseline with regards to demographic and clinical data. No effect of SMC021 on preventing new vertebral fractures was observed, nor was any effect seen on new hip or non-vertebral fractures. Women receiving SMC021 had a mean 1.02% (±0.12%) increase in lumbar spine bone mineral density (BMD) compared with a mean 0.18% (±0.12%) increase in the placebo group by the end of the study (pplacebo arm at 12 and 24months, but not at 36months. No change in quality of life between groups, assessed by the Qualeffo-14 questionnaire, was observed in either group between baseline and month 36. Pharmacokinetics analysis confirmed exposure to SMC021, but the drug levels were markedly lower than expected. Approximately 92% of subjects in each treatment group experienced an adverse event (AE), the majority of which were mild or moderate in intensity. AEs associated with SMC021 were primarily of gastrointestinal origin and included nausea, vomiting and abdominal pain, as well as hot flushes which were the reason for the slightly higher drop-out rate in the active treatment arm compared to placebo. The number of severe AEs was low in both groups. Thirty-five deaths were reported but none were considered treatment-related. Due to the lack of efficacy in preventing fractures, the development of the orally formulated calcitonin was terminated despite the promising results in earlier studies. PMID:27462009

  1. 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.

  2. 糖尿病患者视网膜病变与降钙素基因相关肽及内皮素的关系%Relationship between diabetic retinopathy and calcitonin gene related peptide and endothelin in diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    苏珂; 龙艳; 胡永玲

    2000-01-01

    Objective To study the relationship between diabetic retinopathy (DR) and calcitonin gene related peptide (CGRP)or endothelin (ET) in diabetes rnellitus. Methods The concentration of calcitonin gene related peptide and endothelin was determinedin 30 normal subjects(group C) and 60 diabetic patients(DM group) by radioimmunoassay . The DM group was sub- divided into threegroups: 20 cases of non diabetic retinopathy group (DM group Ⅰ ); 22 cases of background diabetic retinopathy group (DM group Ⅱ ); 18cases of proliferative diabetic retinopathy group (DM group Ⅲ ). Results The concentration of calcitonin gene related peptide in diabetesmellitus group was lower than that in group C( P 0.05). The ET in DM group Ⅲ was markedly higherthan that in group C( P 0.05),DMⅢ组与对照组比较差异有显著性(P<0.01)。CGRP与ET水平存在直线负相关关系。结论CGRP水平降低可能是糖尿病视网膜病变的致病作用因素之一,增殖期糖尿病视网膜病变可能与CGRP显著减少、ET明显增高密切相关。

  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. 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.

  5. 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.

  6. 慢性阻塞性肺疾病急性加重期患者降钙素原及超敏C反应蛋白的检测意义%Significance of the detection of calcitonin and high sensitive C reactive protein in patients with acute exacerbation of chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    陈仁君; 蔡艳

    2016-01-01

    Objective:To explore the significance of the detection of calcitonin and high sensitive C reactive protein in patients with acute exacerbation of chronic obstructive pulmonary disease.Methods:80 patients with chronic obstructive pulmonary disease were selected.39 cases were acute exacerbation group.41 cases were stable phase group.At the same time,40 healthy persons were selected as the normal group.Serum calcitonin and high sensitive C reactive protein of all persons were detected.Results:In the acute exacerbation group,serum calcitonin and high sensitive C reactive protein were significantly higher than the stable phase group and normal group.In the stable phase group,the level of high sensitive C reactive protein was higher than the normal group(P<0.05).In death cases,serum calcitonin and high sensitive C reactive protein were significantly higher than survival cases(P<0.05).Conclusion:Combined detection of serum calcitonin and high sensitive C reactive protein was helpful to understand the severity and prognosis of patients with chronic obstructive pulmonary disease.It was helpful for clinical diagnosis and treatment.%目的:探讨慢性阻塞性肺疾病急性加重期患者降钙素原及超敏C反应蛋白的检测意义。方法:收治慢性阻塞性肺疾病患者80例,其中39例为急性加重组,其余41例为稳定期组,同时选择健康者40例为正常组,测定所有入组者的血清降钙素原及超敏C反应蛋白水平。结果:急性加重组血清降钙素原和超敏C反应蛋白水平均高于稳定组和正常组,稳定组超敏C反应蛋白水平高于正常组(P<0.05)。死亡病例的血清降钙素原和超敏C反应蛋白水平均高于生存病例(P<0.05)。结论:血清降钙素原及超敏C反应联合检测有助于了解慢性阻塞性肺疾病患者病情严重程度及预后,有助于临床诊治。

  7. 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.

  8. Usefulness of Serum Calcitonin in Patients Without a Suspicious History of Medullary Thyroid Carcinoma and with Thyroid Nodules Without an Indication for Fine-Needle Aspiration or with Benign Cytology.

    Science.gov (United States)

    Rosario, P W; Calsolari, M R

    2016-06-01

    This study evaluated the usefulness of serum calcitonin (Ctn) in subjects without a suspicious history of medullary thyroid carcinoma (MTC) and with nodular thyroid disease without an indication for fine-needle aspiration (FNA) or with benign cytology. This was a prospective study that evaluated 421 patients with nodular disease without an indication for FNA and 602 patients with benign cytology. Patients with basal Ctn>10 pg/ml were submitted to calcium stimulation testing. Patients with stimulated Ctn>100 pg/ml were submitted to total thyroidectomy. Basal Ctn was10 pg/ml, 16/22 exhibited stimulated Ctn>100 pg/ml. Two of these 16 patients had MTC. The 2 patients with MTC had undetectable basal Ctn 6 months after surgery. Using a cut-off of 30 pg/ml in women and 60 pg/ml in men for basal Ctn, the 2 cases of MTC of our series would have been identified and there would have been no false-positive case. It should be noted that 14/16 patients with stimulated Ctn>100 pg/ml were false-positive cases. Although uncommon, even subjects without a suspicious history and with nodular thyroid disease without an indication for FNA or with benign cytology can have MTC. The measurement of Ctn permits the diagnosis of these cases. Our results favor the hypothesis that basal Ctn could be superior to stimulated Ctn. PMID:27203410

  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. Effect of hyperbaric oxygenation on plasma endothelin and calcitonin gene related peptide in hypertensive cerebral hemorrhage patients%高压氧对高血压脑出血患者血浆ET、CGRP的影响

    Institute of Scientific and Technical Information of China (English)

    赵波; 吕云利; 姚向荣; 廖军

    2012-01-01

    目的 探讨高压氧对高血压脑出血患者血浆内皮素(ET)、降钙素基因相关肽(CGRP)的影响.方法 选择70例高血压脑出血患者,随机分为高压氧治疗组和常规治疗组,每组35例;2组均予常规治疗,高压氧治疗组在常规治疗的基础上于入院后第5天生命体征稳定后进行高压氧治疗,每天1次,共治疗14d.采用放射免疫法在治疗不同时间点(24h、5d、14d、21d)分别测血浆ET、CGRP值.另选择35例健康体检者作为正常对照组.结果 入院时24h高压氧治疗组及常规治疗组ET值高于正常对照组,CGRP值低于正常对照组.入院后(14d、21d)高压氧治疗组ET值低于常规治疗组,CGRP值高于常规治疗组.结论 高压氧治疗可以降低血浆ET水平,提高CGRP含量,从而改善高血压脑出血患者预后,并对继发性脑损伤有一定的治疗作用.%Objective It is to investigate the effect of hyperbaric oxygenation on plasma endothelin( ET ) and calcitonin gene-related peptide( CGRP ). Methods 70 hypertensive cerebral hemorrhage patients were randomly divided into hyperbaric oxygenation therapeutic group and conventional therapy group ( 35 cases in each group ). Beside the conventional therap,patients in hyperbaric oxygenation therapeutic group also received hyperbaric oxygenation in the fifth day after being in hospital if the body signs were stable,once a day and for 14 days. The developments of ET and CGRP levels in serum from both groups were monitored ( 24 h, 5 d, 14 d, 21 d ) with radioimmunoassay ,35 healthy people ( control group ) were enrolled in this stud-y. Results The level of ET was higher and the level of CGRP was lower in treatment group and conventional therapy group than that in normal control group in 24 h after being in hospital. The level of ET was lower and the level of CGRP was higher in hyperbaric oxygenation therapy group after therapy at 14 d and 21 d than that in conventional therapy( P <0. 05 ). Conclusion Hyperbaric

  11. 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.

  12. 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

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. 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

    Directory of Open Access Journals (Sweden)

    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

  16. 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

    Institute of Scientific and Technical Information of China (English)

    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

  17. 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

  18. An Experimental Study on the Effects of Local Vibration on Concentration of Plasma Endothelin and Calcitonin Gene-related Peptide%局部振动对家兔血浆内皮素和降钙素基因相关肽浓度的影响

    Institute of Scientific and Technical Information of China (English)

    林立; 张强; 曾晓立; 张凯; 王林

    2001-01-01

    [目的] 探讨局部振动对血浆内皮素(endothelin,ET)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)浓度的影响及其意义。 [方法] 对不同接振时间、不同接振强度的家兔进行了血浆ET和CGRP浓度的测定与分析。 [结果] 实验组家兔血浆ET浓度较对照组有升高趋势,而CGRP浓度有下降趋势;随接振时间的延长和接振剂量的增大,变化更明显。 [结论] 局部振动可导致血浆ET浓度的升高和CGRP浓度的降低,这种变化可能与振动性血管损伤的发生机制有关。%[Objective] The aim of this study was to explore the effects of local vibration on the concentrations of plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) and their meanings. [Methods] The concentrations of plasma ET and CGRP were measured and analyzed in rabbits exposed to different vibration power with different exposure period. [Results] There was a increasing tendency in plasma ET level and a decreasing tendency in plasma CGRP level in experiment groups than those in control group,which changed more largely with prolonging exposure period and enhancing vibration power. [Conclusion] Local vibration can result in increase in the concentration of plasma ET and decrease in the concentration of plasma CGPR in rabbits. Those changes might be related to the mechanism of vibration-induced vascular impairment.

  19. Interventional effect of calcitonin on insulin like growth factor 1 gene expression in osteoblasts under simulated microgravity%模拟失重状态下成骨细胞胰岛素样生长因子1基因表达与降钙素的干预

    Institute of Scientific and Technical Information of China (English)

    苏嘉霖; 张桦; 杨理婷; 杨锐; 王脉桃; 黄震

    2011-01-01

    BACKGROUND: Space flight, bed-ridden state of low-gravity load will cause bone metabolic disorder which includes bone absorption and bone formation abnormal, leading to bone loss, decreased bone mineral density. Researches have showed that calcitonin can promote osteoblastic activity and mRNA expression of insulin like growth factor 1 (IGF-1).OBJECTIVE: To observe the effects of calcitonin on osteoblastic activity and mRNA expression of IGF-1 in vitro under simulated microgravity.METHODS: Osteoblasts were collected from newborn SD mouse by means of double enzyme digestion. The osteoblasts were polymerized and encapsulated the cells inside alginate carriers in Cacl2 solution. All cells were assigned into normal gravity,simulated microgravity and simulated microgravity + calcitonin (10, 40 and 80 IU/L) groups. Osteoblasts were cultured for 72 hours in simulated microgravity and normal gravity in the three-dimensional rotating vessel. The proliferation and apoptosis of the osteoblasts and alkaline phosphatase (ALP) activity were detected, in addition, the expression of IGF-1 , ALP and osteocalcin were measured by RT-PCR.RESULTS AND CONCLUSION: Compared with the normal gravity group, the osteoblasts proliferation rate and secretion of ALP were decreased, and the expression of IGF-1, ALP, osteocalcin mRNA were reduced in the simulated microgravity group (P<0.01).Compared with the simulated microgravity group, osteoblasts proliferation rate, IGF-1 , ALP, osteocalcin mRNA were increased in the simulated microgravity + calcitonin group, but no dose-dependent manner could be found. The findings demonstrated that calcitonin can improve osteoblast proliferation and secretion functions via up-regulating IGF-1 mRNA expression in simulated microgravity.%背景:航天飞行、长期卧床等低重力负荷状态会引起骨吸收和骨形成的代谢紊乱,导致骨质疏松.有研究显示降钙素有直接促进成骨细胞增殖的作用,并可增加成骨

  20. 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.

  1. THE EFFECT OF CORTICAL SPREADING DEPRESSION ON CALCITONIN GENE-RELATED PEPTIDE AND SUBSTANCE P LEVELS IN SERUM OF RATS%皮层扩布性抑制对血浆降钙素基因相关肽与P物质的影响

    Institute of Scientific and Technical Information of China (English)

    邱恩超; 于生元; 李凤鹏; 刘若卓; 石宏; 景向红

    2014-01-01

    目的:建立偏头痛大鼠皮层扩布性抑制(cortical spreading depression,CSD)模型,研究CSD对大鼠血浆降钙素基因肽(calcitonin gene-related peptide,CGRP)和P物质(substance P,SP)的影响.方法:大鼠随机分为CSD组(n=10)、对照组(n=10),分别用氯化钾溶液及生理盐水浸润滤纸片刺激枕叶皮层,在额叶皮层记录CSD波,利用放射免疫技术测定大鼠血浆中的CGRP、SP水平,进行成组t检验比较.结果:CSD组大鼠记录到CSD波,对照组大鼠未记录到CSD波;CSD组大鼠血浆CGRP、SP水平高于对照组(P<0.05).结论:利用氯化钾溶液浸润滤纸片刺激大鼠枕叶皮层成功建立了CSD模型,CSD使血浆CGRP、SP水平增加,说明CSD可能通过一定的机制激活了三叉神经血管反射,进而导致偏头痛的发生.

  2. Effects of electroacupuncture at zusanli on plasma endothelin, nitric oxide and calcitonin gene related peptide%电针足三里对应激大鼠血浆内皮素、一氧化氮、降钙素基因相关肽的影响

    Institute of Scientific and Technical Information of China (English)

    顾炳权; 秦明; 黄裕新; 刘树林

    2002-01-01

    Objective To observe the effects of electroacupuncture (EA) on plasma levels of endothelin (ET), nitric oxide (NO), and calcitonin gene related peptide (CGRP) in stress rats.Methods 32 SD rats were randomly divided into 4 groups: control group, stress group, EA after stress and stress after EA group. The plasma levels of NO and CGRP were measured by radioimmunoassay methods the level of NO were measured by biochemical methods. Result Compared with control group,NO level of stress group decreased from (22.7± 3.8)μ mol/L to (18.8± 5.2) μ mol/L (P< 0.05), but ET increased from (140± 17) ng/L to(177± 23)ng/L (P< 0.05); compared with stress group, NO level of EA after stress and stress after EA group increased from (18.8± 5.2) μ mol/L to (23.3± 4.1) μ mol/L and (22.9± 4.1) μ mol/L (P< 0.05); CGRP level increased from (145± 6) ng/L to (184± 22) ng/L (P< 0.05); but ET level decreased from (177± 23) ng/L to (134± 8) ng/L,(140± 20) ng/L (P< 0.05),in which CGRP of stress after EA group has no statistic significance.Conclusion EA at zusanli point can increase gastric mucosa blood flow and protect gastric mucosa.Its mechanism may be related to the regulation of plasma level of ET, NO and CGRP.

  3. 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

  4. Effect of calcitonin on bone mineral density and biomechanics around the artificial prosthesis in the rabbit of diabetic osteoporosis model%降钙素对大白兔糖尿病骨质疏松模型假体骨密度及生物力学的影响

    Institute of Scientific and Technical Information of China (English)

    刘亚非; 陈百成; 张兵; 侯义梅

    2009-01-01

    Objective To investigate the influence of calcitonin on bone mineral density and biomechanics around the artificial pros-thesis in ovariectomized diabetic rabbit model. Methods Fourteen femina New Zealand white rabbits at the age of 5 months old were select-ed, which weight 2.24 -2.65kg, averaging 2.26kg. First, the model of rabbit with diabetic osteoporosis was successfully established by the compound method of ovariectomy plus streptozotocin. Osteotomy in the middle part of femur was performed in both groups, fixation of artifi-cial prosthesis was done with 3.0 kirschner wire. After that, Rabbit models with diabetic osteoporosis were randomly divided into experimen-tal group and control group. Rabbits in the experimental group were treated with calcitonin 6U intramuscular injection once every other day. In control group, intramuscular injection of normal saline solution 1.5ml once every three days. Rabbit models of two groups were sacrificed in the 24th week. The BMD of the region of interest (ROI) around the prosthesis were detected before experiment and 8, 16 and 24 weeks after injection. After rabbits were killed, experimental femurs in both groups were complete removal and soft tissues were rejected. Determi-nation of the pull-out and torsion bone biomechanics experiments of prosthesis was done in both groups respectively. Results The BMD of ROI in the experimental group before operation was (0.1863±0.004)g/cm2 and (0.1753±0.005)g/cm2 in 24 weeks after operation, in control group before operation was (0.1865±0.002)g/cm2 and (0.1638±0.005)g/cm2 in 24 weeks after operation. There were significant difference between the two groups(P < 0.05). Biomechanical show that the pull-out strength in the experimental group was (312.68±8.73 )N/cm2 and (205.43±12.45 ) N/cm2 in control group. There were significant difference between the two groups(P < 0.05). The tor-sion strength in experimental group was (80.47±2.51) N/cm2 and (38.52±0.64) N/cm2 in control group

  5. The effects of flunarizine hydrochloride on plasma calcitonin gene-related peptide and substance P levels after cortical spreading depression in rats%盐酸氟桂利嗪对大鼠皮层扩布性抑制模型血浆CGRP及SP浓度的影响

    Institute of Scientific and Technical Information of China (English)

    邱恩超; 于生元; 李凤鹏; 刘若卓; 董钊; 姜磊; 石宏; 景向红

    2014-01-01

    目的:建立偏头痛大鼠皮层扩布性抑制(cortical spreading depression, CSD)模型,研究盐酸氟桂利嗪干预后对CSD及血浆降钙素基因相关肽(calcitonin-gene related peptide, CGRP)、P物质(substance P, SP)浓度的影响。方法大鼠随机分为对照组、CSD组、氟桂利嗪干预组,利用氯化钾溶液刺激法建立CSD模型,采用放射免疫技术测定大鼠血浆中的CGRP、SP浓度。结果对照组未记录到CSD波;氟桂利嗪干预组与CSD组比较, CSD波的潜伏期延长[氟桂利嗪干预组(167.90±25.18s) vs.CSD组(130.90±13.30s)](P<0.01),个数减少[氟桂利嗪干预组(4.50±1.84) vs.CSD组(8.50±2.07)](P<0.01),波幅降低[氟桂利嗪干预组(11.40±4.12 mv) vs.CSD组(24.40±3.57 mv)](P<0.01);关于血浆CGRP浓度和SP浓度,CSD组(CGRP,32.95±11.61 pg/mL;SP,27.80±7.51 pg/mL)及氟桂利嗪干预组(CGRP,25.13±5.67 pg/mL;SP,19.45±6.10 pg/mL)均高于对照组(CGRP,14.44±6.39 pg/mL;SP,12.36±4.22 pg/mL)(P<0.01),氟桂利嗪干预组(CGRP,25.13±5.67 pg/mL;SP,19.45±6.10 pg/mL)低于CSD组(CGRP,32.95±11.61 pg/mL;SP,27.80±7.51 pg/mL)(P<0.05)。结论盐酸氟桂利嗪能够抑制CSD的发生,使大鼠CSD模型的血浆CGRP、SP浓度降低。%Objective To explore the effects of flunarizine hydrochloride on plasma calcitonin gene-related pep-tide and substance P levels after CSD in a rat migraine model of cortical spreading depression (CSD). Methods Thirty adult rats were randomly and evenly divided into three groups:control Group, CSD group and flunarizine group. The CSD waves were evoked by application of potassium chloride on brain surface with filter paper. Funarizine hydrochloride was intravenously administered to rats five minutes prior to application of potassium chloride. The plasma levels of CGRP and SP were measured by using radioimmunity assay. Statistical analyses were performed using two-sample t test and analy-sis of variance. Results CSD waves

  6. 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.

  7. 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

  8. Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin

    OpenAIRE

    Plotkin, Lilian I.; Weinstein, Robert S; Parfitt, A. Michael; Roberson, Paula K.; Manolagas, Stavros C.; Bellido, Teresita

    1999-01-01

    Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition. We have tested the hypothesis that BPs suppress apoptosis in these cell types. Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10–9 to 10–6 M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced ...

  9. 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

  10. Effect of electroacupuncture treatment on pain behavior and calcitonin-gene related peptide expression in cancer induced bone pain-morphine tolerance rat model%电针对骨癌痛-吗啡耐受大鼠痛行为和降钙素基因相关肽的影响

    Institute of Scientific and Technical Information of China (English)

    司马蕾; 刘波涛; 厉建春; 刘乃刚; 张韫

    2013-01-01

    目的 探讨电针治疗对骨癌痛吗啡耐受模型大鼠痛行为的影响以及背根神经节降钙素基因相关肽(CGRP)表达的变化.方法 40只SD大鼠随机分为4组,每组10只:假手术组(Sham)、骨癌痛+吗啡耐受组(BM)、骨癌痛+电针组(BE)和骨癌痛+吗啡耐受+电针组(BME).BM、BE和BME组制备胫骨癌痛模型,接种后第7天3组分别实施吗啡、电针、吗啡+电针治疗,连续9d.电针选择足三里(ST36)和三阴交(SP6)穴位.痛行为采用机械刺激缩足阈值测定,以50%缩足阈表示.免疫组织化学测定背根神经节CGRP表达水平.结果 电针治疗第5天,BME组50%缩足阈值(10.9±0.8)g,与BM组[(8.7±0.6)g]和BE组[(6.2±0.9)g]相比,差异有统计学意义(P<0.01),并持续至第9天.BME组背根神经节CGRP免疫阳性表达的IOD值(9026.5±1827.4),与BM组(14803.1±2086.7)和BE组(15730.6±2712.5)比较,差异有统计学意义(P<0.01).结论 电针能够改善骨癌痛-吗啡耐受大鼠机械痛阈,机制可能与减少背根神经节CGRP过度释放有关.%Objective To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP)-morphine tolerance rat model and the expression of calcitonin-gene related peptide(CGRP) immunohistochemisty in dorsal root ganglion (DRG).Methods Forty SD rats were divided into four groups:sham group,CIBP + morphine tolerance group (BM),CIBP + electroacupuncture group (BE),and CIBP + morphine tolerance + electroacupuncture group (BME).BM,BE and BME groups were prepared CIBP model by carcinoma cell tibia implanted.After six days,the three CIBP groups accepted treatment of morphine,electroacupuncture,and morphine combined electroacupuncture,separately,nine days continuously.Acupoints were selected Zusanli (ST36) and Sanyinjiao (SP6).50% mechanical withdraw threshold was evaluated by mechanical stimulation.CGRP expression in dorsal root ganglion was detected by immunohistochemisty.Results After five days of

  11. 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

  12. 中枢和周围神经损伤对降钙素基因相关肽含量及骨折愈合的影响%Effect of central and peripheral nerve injuries on contents of calcitonin gene-related peptide and fracture healing

    Institute of Scientific and Technical Information of China (English)

    汤池; 姜保国; 王天兵; 韩娜; 付中国; 张培训; 殷晓峰; 张宏波; 张殿英

    2008-01-01

    目的 研究骨折合并中枢和周围神经损伤后大鼠的血浆、脊髓前角运动神经元及背根神经节中降钙素基因相关肽(calcitonin gene-related peptide,CGRP)的含量变化及对骨折愈合的影响. 方法 健康成年SD大鼠72只,随机平均分成4组:左侧胫骨骨折组(A组)、左侧坐骨神经损伤+左侧胫骨骨折组(B组)、T9-11脊髓横断+左侧胫骨骨折组(C组)和右侧大脑皮层损伤+左侧胫骨骨折组(D组).每组大鼠于伤后即刻、2 d、1周、2周及4周,放射免疫法测定血清中CGRP含量;于伤后1周、2周及4周对骨折处拍摄x线片,放射免疫法测定脊髓前角运动神经元及背根神经节中CGRP含量;2周取骨折局部骨痂做HE染色. 结果 各组大鼠1周及2周X线片骨折线清晰,4周除B组外,其余各组骨折线消失.2周HE染色显示骨痂量变化:B组少于A组;C组及D组多于A组.各组大鼠在血清中及脊髓前角运动神经元中各时间点CGRP含量变化差异无统计学意义(P>0.05).在脊髓背根神经节中CGRP含量变化:1周时,B组及D组与A组比较,差异无统计学意义(P>0.05),C组低于A组(P0.05),但D组高于B组(P0.05). Changes of CGRP con-centration in dorsal root ganglion were as follows: one week after injury, there was no apparent statistical difference in Groups B and D compared with Group A (P > 0.05), but Group A showed more CGRP than Group C (P 0.05), but CGRP in Group D was more than that in Group B (P < 0.05) and CGRP in Group C more than Group A (P <0.01); four weeks after injury, CGRP concentration was elevated in all groups especially Group C compared with Group A (P < 0.01). Conclusions When fracture is combined with peripheral nerve injury, the healing process can be slowed down. In contrast, fracture combined with spinal'injury and cerebral cortex injury will accelerate healing process, when CGRP may exert positive effect.

  13. 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

  14. 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

  15. 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);

  16. 携带人降钙素基因相关肽基因的重组逆转录病毒的构建及鉴定%Construction and identification of recombinant retroviral vector pLNCX2-human calcitonin gene-related peptide α

    Institute of Scientific and Technical Information of China (English)

    王义生; 皮国富; 王亚寒; 赵国强; 李月白

    2012-01-01

    目的 构建、鉴定携带人降钙素基因相关肽α(hCGRPα)的重组逆转录病毒载体pLNCX2-hCGRPα.方法 采用基因工程技术,双酶切消化后回收438 bp的hCGRPα cDNA片段和6.1kb的pLNCX2载体片段,纯化后按摩尔比7∶1混合,将降钙素基因相关肽基因片段克隆至逆转录病毒载体pLNCX2上,序列测定、对比.鉴定后用脂质体法转染PT67细胞进行病毒包装扩增,感染NIH3T3细胞,观察细胞克隆,测定病毒滴度.结果 酶切、测序结果与hCGRPα基因重组逆转录病毒载体的预期结果一致,分别为6.1kb和438 bp,与空载体和目的基因大小相符.包装、扩增获得病毒滴度达1.7×106 pfu/ml,对NIH3T3细胞有较高的感染效率.结论 成功构建重组逆转录病毒pLNCX2-hCGRPα,为进一步的基因治疗研究奠定了实验基础.%Objective To construct and identify the recombinant retroviral vector encoding human calcitonin gene-related peptideα (hCGRPα) gene.Methods Using genetic engineering techniques,the fragment of hCGRPα cDNA and the fragment of pLNCX2 carrier,respectively 438 bp and 6.1 kb,were recovered after double digestion,then mixed according to molar ratio of 7∶1 after purification.The hCGRPα gene was cloned into the retroviral vector pLNCY2.High titer viral particles of pLNCX2- hCGRPα were obtained after transfection of PT67 cells by Lipofectine 2000.Then the recombinant retrovirus was transfected into NIH3T3 cells and the titer was measured.Results Restriction,and sequencing analysis confirmed that the hCGRPα cDNA was successfully inserted into the retroviral vector.The titer of recombinant retrovirus with hCGRPα gene was 1.7 × 106 pfu/ml and the retrovirus was effectively transfected into NIH3T3 cells.Conclusion The recombinant retroviral vector pLNCX-hCGRPα had been constructed successfully,which can be used for further investigation on gene therapy.

  17. Correction: Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding

    OpenAIRE

    Banerjee, Sugato; Evanson, Janel; Harris, Erik; Lowe, Stephen L; Speth, Robert C.; Thomasson, Kathryn A; Porter, James E.

    2006-01-01

    This is a correction article. After publication of this work [1], we became aware of the fact that Robert C. Speth was not included as an author. Dr. Speth put a considerable amount of time and effort into developing and preparing the radiopeptide used to carry out the radioligand binding studies reported in this manuscript and therefore should have originally been included as an author. We apologize to Dr. Speth for any inconvenience that this oversight might have caused and thank him for hi...

  18. 降钙素基因相关肽通过Hippo通路调控小鼠骨髓间充质干细胞成骨分化的实验研究%Calcitonin gene-related peptide-induced osteogenic differentiation of mouse bone marrow stromal cells through Hippo pathwayin vitro

    Institute of Scientific and Technical Information of China (English)

    王飞; 张慧宇; 窦予昕; 李适廷; 张纲; 谭颖徽

    2016-01-01

    目的:前期研究发现降钙素基因相关肽(CGRP)能够促进成骨细胞的生物学活性,为了进一步揭示CGRP在骨修复中的作用,检测CGRP对小鼠骨髓间充质干细胞(BMSCs)成骨分化的影响,并对Hippo通路在这个过程中的作用进行了初步探讨。方法在体外诱导培养的BMSCs中加入不同浓度的CGRP,处理48 h后测试碱性磷酸酶(ALP)活性,以筛选的优势浓度;处理7 d后进行茜素红染色,分别检测细胞的分化情况。应用Western blot检测CGRP作用于BMSCs后,Hippo通路核心分子Mst1/2蛋白磷酸化的表达水平;利用Hippo通路抑制剂维替泊芬(Verteporfin)阻断下游Yap信号,逆转录聚合酶链反应检测其对成骨相关因子Ⅰ型胶原蛋白(ColⅠ)、Runt相关转录因子2(Runx2) mRNA的表达影响。结果 ALP活性检测结果显示,与空白对照组相比,10-9、10-8、10-7 mol·L-1浓度范围的CGRP都能显著促进小鼠ALP活性的增加(P<0.05),以10-8 mol·L-1浓度的CGRP为最佳刺激浓度。用10-8 mol·L-1浓度的CGRP处理后,茜素红染色显示钙化结节明显增多。CGRP能够显著上调p-Mst1/2蛋白的表达(P<0.05);当运用了抑制剂Verteporfin时,显著降低了CGRP诱导的Runx2、ColⅠ mRNA的表达(P<0.05)。结论 CGRP能够促进小鼠BMSCs的成骨分化,且Hippo信号通路介导了CGRP作用于小鼠BMSCs成骨分化的过程。%Objective Previous studies have clarified that calcitonin gene-related peptide (CGRP) can promote the biological activity of osteoblasts. To further reveal the role of CGRP in bone repair, we studied its influence on osteogenic differentiation of mouse bone marrow stromal cells (BMSCs) and initially explored the effect of the Hippo signaling pathway with this process. Methods BMSCs were induced to osteogenic differentiate osteoblasts by different concentrations of CGRP for a screening of the optimal concentration

  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. 辣椒素对大鼠面部皮肤降钙素基因相关肽和一氧化氮合酶阳性神经纤维的影响%Effect of capsaicin on calcitonin gene-related peptide and nitric oxide synthase-positive nerve fiber in rat facial skin

    Institute of Scientific and Technical Information of China (English)

    丁继固; 茹立强

    2005-01-01

    BACKGROUND: The effect of external application of capsaicin in the treatment of superficial pain has been recognized, but its effect against trigeminal neuralgia by direct action on the nerve ending or nerves in the hypodermis or deep tissues awaits intensive investigation.OBJECTIVE: To observes the effect of subcutaneous injection of capsaicin on calcitonin gene-related peptide (CGRP) and nitric oxide synthase(NOS)-positive nerve fibers in rat facial skin.SETTING: Teaching and Research Division of Anatomy, Xianning Medical College, and Department of Neurobiology, Tongji Medical College of Huazhong University of Science and Technology.MATERIALS: This experiment was conducted in the Laboratory of Neurobiology, Tongji Medical College, between October and December 2003.Twenty healthy Wistar rats of either sex with body mass of 120-170 g were used.METHODS: The rats received subcutaneous injection of capsaicin for treatment of the suborbital branch of the trigeminal nerve on the right side,with the left side serving as the control side. According to the doses of capsaicin applied, the rats were divided into 4 groups, namely 20, 30, 50and 100 μL capsaicin groups with 5 rats in each group. Twenty-four hours after the injections, samples were obtained and cut into slices for microscopic observation and the expressions of CGRP and NOS were examined immunohistochemically.MAIN OUTCOME MEASURES: [1] Changes of CGRP and NOS-positive nerve fibers on the experimental side and image analysis of the mean absorbance of CGRP and NOS; [2] changes of characteristic behaviors and body signs of the rats.RESULTS: Totally 20 rats entered the result analysis. [1] Behavioral change: A few minutes after subcutaneous injection of capsaicin, the rats exhibited a series of characteristic behavioral and symptomatic changes,which gradually diminished or even vanished with the increase of the doses. [2] Microscopic changes: On the experimental side, no obvious difference was noted in the

  1. Effect of calcitonin gene-related peptide on anoxia-reoxygenation induced injury to neonatal rat cardiomyocytes incubated in high glucose medium%降钙素基因相关肽对高糖下新生大鼠心肌细胞缺氧复氧损伤的影响

    Institute of Scientific and Technical Information of China (English)

    陈璐; 赵鑫; 郭政

    2014-01-01

    目的 评价降钙素基因相关肽(CGRP)对高糖下新生大鼠心肌细胞缺氧复氧(A/R)损伤的影响.方法 取原代培养的出生1 ~3 d SD大鼠心肌细胞,在含有10%胎牛血清培养基中培养,细胞接种于6孔细胞培养板,接种密度10×105/ml,3 ml/孔,采用随机数字表法,将其分为5组(n=9),正常糖浓度对照组(NG组)用正常糖浓度(葡萄糖5.5 mmol/L)培养基孵育细胞72 h;高糖对照组(HG组)用高糖(葡萄糖25.0 mmol/L)培养基孵育细胞72 h;HG+ A/R组用高糖培养基孵育细胞72 h后,行缺氧3h,复氧2h;HG+ A/R+ CGRP组用高糖培养基孵育细胞72 h后加入CGRP(终浓度为10-8 mol/L),1h后行缺氧3h,复氧2h;HG+ MR+ CGRP+ CGRP8-37组用高糖培养基孵育细胞72 h后加入CGRP(终浓度为10-8 mol/L)和CGRP8-37(CGRP受体拮抗剂,终浓度10-7 mol/L),1h后行缺氧3h,复氧2h.处理后收集细胞,采用TUNEL法检测心肌细胞凋亡情况,计算凋亡指数(AI).于缺氧3h和复氧2h时分别收集细胞培养液,测定乳酸脱氢酶(LDH)活性.结果 与NG组比较,HG组AI、细胞培养液LDH活性升高(P<0.01);与HG组比较,HG+ A/R组AI、细胞培养液LDH活性升高(P<0.01);与HG+ A/R组比较,HG+ A/R+ CGRP组AI、细胞培养液LDH活性降低(P<0.01),HG+ A/R+ CGRP+CGRP8-37组上述指标比较差异无统计学意义(P>0.05);与HG+ A/R+ CGRP组比较,HG+ A/R+ CGRP+ CGRP8-37组AI、细胞培养液LDH活性升高(P<0.01).结论 CGRP可通过与CGRP受体结合减轻高糖下新生大鼠心肌细胞缺氧复氧损伤.%Objective To evaluate the effect of calcitonin gene-related peptide (CGRP) on anoxiareoxygenation (A/R)-induced injury to neonatal rat cardiomyocytes incubated in high glucose medium.Methods Cardiomyocytes were obtained from 1-3-day old Sprague-Dawley rats and cultured in the culture medium containing 15% bovine calf serum and then seeded onto 6-well plates at a density of 10 × 105/ml (3 ml/well).The cells were randomly divided into 5 groups (n =9

  2. 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.

  3. 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

  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. 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

  6. 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...

  7. 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...

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

    DEFF Research Database (Denmark)

    Edvinsson, Lars; Chan, Kayi Y; Eftekhari, Sajedeh;

    2010-01-01

    in the absence or presence of telcagepant. Arterial slices were stained for RAMP1, CLR and actin in a double immunofluorescence staining. RESULTS: In both arteries, we found that: (i) telcagepant was devoid of any contractile or relaxant effects per se; (ii) pretreatment with telcagepant antagonised the α......CGRP-induced relaxation in a competitive manner; and (iii) immunohistochemistry revealed expression and co-localisation of CLR and RAMP1 in the smooth muscle cells in the media layer of both arteries. CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral...

  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. Flupirtine inhibits calcitonin-gene related peptide release from rat brainstem in vitro.

    Science.gov (United States)

    Tringali, Giuseppe; Greco, Maria Cristina; Capuano, Alessandro; Guerriero, Giuseppe; Currò, Diego; Navarra, Pierluigi

    2012-01-11

    We have previously shown that the nonopioid analgesic flupirtine possesses analgesic activity in the orofacial formalin test in vivo in the rat. However, this paradigm does not allow to distinguish between central and peripheral site of action of the drug. In this study we used a recently characterized in vitro model, consisting in acute rat brainstem explants, to investigate whether flupirtine analgesia may be, at least in part, attributed to interference with neurotransmission between the first and the second order neurons of the trigeminal system, occurring within the brainstem. We used acute rat brainstem explants; CGRP released into the incubation medium was taken as a marker of CGRP release from central terminals of trigeminal ganglion afferent neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of flupirtine, alone or with putative antagonist XE-991. We found that flupirtine inhibits in a concentration-dependent manner both basal and capsaicin-stimulated CGRP release from rat brainstem. This effect is mimicked by the flupirtine analogue retigabine, and is counteracted by the Kv7 blocker XE-991. These findings provide in vitro evidence that the analgesic activity of flupirtine may be related to interference with pain neurotransmission at the brainstem level. Pharmacological data suggests that such effect is related to opening of Kv7 channels on first-order neuronal nerve ending, and the subsequent inhibition of neurotransmitter release, since the effect is mimicked by the Kv7 opener retigabine and is counteracted by the Kv7 blocker XE-991. PMID:22155095

  11. Use of Calcitonin in Recalcitrant Phantom Limb Pain Complicated by Heterotopic Ossification

    OpenAIRE

    Ricardo Viana; Michael WC Payne

    2015-01-01

    A common complication following amputation is phantom sensation, which may include experiencing pain in the phantom limb. This study details the management of phantom limb pain in a 72-year-old man, in whom comorbid heterotopic ossification was present. In addition, the authors provide a review of the literature regarding phantom limb pain management, and summarize the current understanding of heterotopic ossification and its possible link to peripheral nerve injury.BACKGROUND: Phantom limb p...

  12. Use of Calcitonin in Recalcitrant Phantom Limb Pain Complicated by Heterotopic Ossification

    Directory of Open Access Journals (Sweden)

    Ricardo Viana

    2015-01-01

    Full Text Available A common complication following amputation is phantom sensation, which may include experiencing pain in the phantom limb. This study details the management of phantom limb pain in a 72-year-old man, in whom comorbid heterotopic ossification was present. In addition, the authors provide a review of the literature regarding phantom limb pain management, and summarize the current understanding of heterotopic ossification and its possible link to peripheral nerve injury.

  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. 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

    .7 (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide of type 1 procollagen. The results indicate that nasal SCT given as a single dose provokes a modest decrease in bone resorption lasting...

  15. Calcitonin gene-related peptide and nitric oxide in the trigeminal ganglion

    DEFF Research Database (Denmark)

    Edvinsson, L; Mulder, H; Goadsby, P J;

    1998-01-01

    Nitric oxide (NO) is a novel neurotransmitter candidate to which a large number of physiological roles has been ascribed. In the present study, immunocytochemistry was used to demonstrate NO synthase (NOS) and to investigate possible co-localization with other neurotransmitters. In the trigeminal...

  16. 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

    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 hy...

  17. 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

    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....... The location of SP-IR appeared to be comparable to CGRP-IR, but in fewer fibres. Dense NPY-IR networks of nerve fibres were closely associated with the fascicles of smooth musculature in the core of the nipple base. In contrast, VIP-IR fibres were only sparsely present, and SOM-IR was not detected...

  18. 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...

  19. 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

    at different dose levels (10(-10), 10(-9), and 10(-8) M) into isolated perfused porcine pancreata. With 5 mmol/L glucose in the perfusate. CGRP at 10(-10) and 10(-9) M increased insulin and glucagon secretion, whereas significant decreases were observed with 10(-8) M. Somatostatin secretion was increased...

  20. Expression of calcitonin gene-related peptide-1 receptor mRNA in human tooth pulp and trigeminal ganglion

    DEFF Research Database (Denmark)

    Uddman, R; Kato, J; Lindgren, P;

    1999-01-01

    -cell bodies, mostly of small to medium size, was encountered. Reverse transcriptase-polymerase chain reaction, using specific sense and antisense primers, detected mRNA expression of the human CGRP1 receptor in the pulp tissue and the trigeminal ganglion. Thus, both CGRP-containing nerve fibres and CGRP1...

  1. Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries

    DEFF Research Database (Denmark)

    Chan, K Y; Edvinsson, L; Eftekhari, S;

    2010-01-01

    internal diameters were studied to assess the potential for differential effects across the coronary vascular bed. The concentration-dependent relaxation responses to human alphaCGRP were greater in distal coronary arteries (i.d. 600-1000 microm; E(max) = 83 +/- 7%) than proximal coronary arteries (i.d. 2......-3 mm; E(max) = 23 +/- 9%), coronary arteries from explanted hearts (i.d. 3-5 mm; E(max) = 11 +/- 3%), and coronary arterioles (i.d. 200-300 microm; E(max) = 15 +/- 7%). Telcagepant alone did not induce contraction or relaxation of these coronary blood vessels. Pretreatment with telcagepant (10 nM to 1...... microM) antagonized alphaCGRP-induced relaxation competitively in distal coronary arteries (pA(2) = 8.43 +/- 0.24) and proximal coronary arteries and coronary arterioles (1 microM telcagepant, giving pK(B) = 7.89 +/- 0.13 and 7.78 +/- 0.16, respectively). alphaCGRP significantly increased cAMP levels...

  2. Localisation and neural control of the release of calcitonin gene-related peptide (CGRP) from the isolated perfused porcine ileum

    DEFF Research Database (Denmark)

    Rasmussen, T N; Schmidt, P; Poulsen, S S;

    2001-01-01

    By immunohistochemistry, CGRP-like immunoreactive (CGRP-LI) nerve fibres were found in the lamina propria along small vessels and in the lamina muscularis mucosae in the porcine ileum. Immunoreactive nerve cell bodies were found in the submucous and myenteric plexus. Upon HPLC-analysis of ileal...... neuroblockers. In addition, the effect of infusion of capsaicin was studied. The basal output of CGRP-LI was 2.9+/-0.7 pmol/5 min (mean+/-S.D.). Electrical nerve stimulation (8 Hz) significantly increased the release of CGRP-LI to 167+/-16% (mean+/-S.E.M.) of the basal output (n=13). This response was...... abolished by infusion of hexamethonium (3x10(-5) M). Infusion of capsaicin (10(-5) M) caused a significant increase in the release of CGRP-LI to 485+/-82% of basal output (n=5). Our results suggest a dual origin of CGRP innervation of the porcine ileum (intrinsic and extrinsic). The intrinsic CGRP neurons...

  3. Calcitonin gene-related peptide (CGRP), peptide YY (PYY) gastrin releasing peptide (GRP) and others in hamster lung and plasma

    International Nuclear Information System (INIS)

    Rabbit antisera to CGRP, PYY, neuropeptide Y (NPY) and GRP were used for immunocytochemical localization of these peptides in lungs of neonate hamsters at birth and 6 d of age and young (70 gm) and adult (107 gm) hamsters. The peroxidase-antiperoxidase method was applied to paraffin sections of tissue fixed in Bouin's or Zamboni's solution. Furthermore, radioimmunoassay (RIA) was used to quantify these peptides in lung tissue and plasma from the young hamsters (n=13). Distinct CGRP-like immunoreactivity (IR) was noted in grouped (NEB) and individual (NEC) neuroendocrine cells at all ages including all airways from trachea (NECs only) to alveoli. In some NEBs this IR coexisted with 5-HT-like IR. PYY- and NPY-like Ir was mainly noted in NEBs and NECs at the level of bronchioles and alveoli, and weak GRP-like IR was present in neuroendocrine-like cells of small airways. Measurable quantities of all peptides were recorded by RIA. Females had higher lung and plasma levels of CGRP and plasma levels of PYY than males and tended to have higher lung levels of GRP. The neuropeptides CGRP, PYY and the analog NPY are putative regulators of local pulmonary blood flow by vasodilation (CGRP) and constriction (PYY, NPY), and GRP is known to regulate peptide release

  4. 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.

  5. 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

    -measure ANOVA showed no interaction between catheter and time of sampling and thus no significant difference in CGRP between the four catheters (P=0.75). CGRP did not change over time in the four compartments (P>0.05). The relative changes in CGRP between baseline and maximal sumatriptan concentration did...

  6. Serum Calcitonin gene-related Petide concentrations in the horse and their relationship to the Systemic Inflammatory Response

    OpenAIRE

    Mitchell, Emma

    2006-01-01

    Systemic inflammation is a leading cause of mortality and morbidity in both human and equine intensive care patients. This systemic inflammatory response may be due to insult from bacterial, viral, fungal or parasitic invasion or from trauma or hypoxemia. Local and systemic release of a wide variety of endogenous pro-inflammatory mediators results in activation of the innate immune system in order to resolve the insult. In sepsis this initial appropriate host response becomes amplified and de...

  7. 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

    -controlled, exploratory, proof-of-concept phase 2 trial, patients aged 18-55 years with five to 14 migraine days per 28-day period were randomly assigned (1:1) via an interactive web response system to receive an intravenous dose of ALD403 1000 mg or placebo. Site investigators, patients, and the sponsor were masked...... group compared with -4·6 (3·6) for the placebo group (difference -1·0, 95% CI -2·0 to 0·1; one-sided p=0·0306). INTERPRETATION: No safety concerns were noted with an intravenous dose of ALD403 1000 mg. This study also provides preliminary evidence for the efficacy of ALD403 in the preventive treatment...

  8. Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo

    DEFF Research Database (Denmark)

    Petersen, K A; Nilsson, E; Olesen, J;

    2005-01-01

    (gCCW) in vivo study. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-alphaCGRP, rat-betaCGRP, amylin and adrenomedullin were compared with the resting...

  9. 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only at doses with 5HT(1B/1D) receptor agonist activity?

    DEFF Research Database (Denmark)

    Knight, Y E; Edvinsson, L; Goadsby, P J

    2001-01-01

    )-mediated effects, that was developed as an anti-migraine drug, and thus was suitable to test whether higher doses of such conformationally restricted triptan analogues could inhibit trigeminal-evoked CGRP release. The superior sagittal sinus (SSS) was stimulated in 14 anaesthetised cats and external jugular vein...

  10. Comparison of the vasoconstrictor effects of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) and zolmitriptan in human isolated coronary arteries

    DEFF Research Database (Denmark)

    Lynch, Joseph J; Regan, Christopher P; Edvinsson, Lars;

    2010-01-01

    to relax to human alphaCGRP, with the CGRP-mediated vasorelaxation completely blocked with 30 microM telcagepant. In coronary vessels at basal tone, zolmitriptan caused a concentration-dependent contraction (pEC50 = 6.9 +/- 0.1; slope 0.94), with the greatest contraction obtained between 1 and 10 micro...

  11. Role of KATP channels in cephalic vasodilatation induced by calcitonin gene-related peptide, nitric oxide, and transcranial electrical stimulation in the rat

    DEFF Research Database (Denmark)

    Gozalov, Aydin; Jansen-Olesen, Inger; Klærke, Dan Arne;

    2008-01-01

    in migraine pathogenesis. We hypothesized that vasodilatation induced by CGRP and the NO donor glyceryltrinitrate (GTN) is mediated via K(ATP) channels. METHODS: We examined the effects of the K(ATP) channel inhibitor glibenclamide on dural and pial vasodilatation induced by CGRP, NO, and endogenously....... In anesthetized rats glibenclamide significantly attenuated CGRP induced dural and TES induced dural/pial artery dilatation (P = .001; P = .001; P = .005), but had no effect on dural/pial vasodilatation induced by GTN. In vitro glibenclamide failed to significantly inhibit CGRP- and GTN-induced vasodilatation....... CONCLUSIONS: These results show that a K(ATP) channel blocker in vivo but not in vitro inhibits CGRP, but not GTN-induced dilatation of dural and pial arteries, a mechanism thought to be important in migraine....

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

    NARCIS (Netherlands)

    Evaristo, Geisa P C; Pinkse, Martijn W H; Chen, Tianbao; Wang, Lei; Mohammed, Shabaz; Heck, Albert J R; Mathes, Isabella; Lottspeich, Friedrich; Shaw, Chris; Albar, Juan Pablo; Verhaert, Peter D E M

    2015-01-01

    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

  13. 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

    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...

  14. Protective role of ellagitannins from Eucalyptus citriodora against ethanol-induced gastric ulcer in rats: impact on oxidative stress, inflammation and calcitonin-gene related peptide.

    Science.gov (United States)

    Al-Sayed, Eman; El-Naga, Reem N

    2015-01-15

    The gastroprotective activity of an ellagitannin-rich fraction obtained from Eucalyptus citriodora (ECF) was investigated against ethanol-induced gastric ulceration in rats. The rats were pretreated with ECF (25, 50 and 100mg/kg) 1h before the administration of absolute ethanol to induce acute gastric ulceration. The gastric lesions were significantly reduced by all doses of ECF. Notably, pre-treatment with ECF (100mg/kg) conferred 99.6% gastroprotection, which is significantly higher than that produced by omeprazole. Moreover, ECF administration markedly increased the mucin content in a dose-dependent manner. The potent gastroprotective effect of ECF could be partly mediated by attenuating ethanol-induced oxidative stress. ECF-pre-treatment markedly increased the depleted GSH and SOD levels in a dose-dependent manner. Moreover, ECF significantly decreased the elevated MDA tissue levels induced by ethanol administration. The results demonstrated that ECF administration exerted a powerful anti-inflammatory activity as evidenced by the reduction in the pro-inflammatory markers; IL-1β, TNF-α, 5-LO and COX-2. Additionally, the caspase-3 tissue levels were significantly reduced in the groups pre-treated with ECF. These results suggest that ECF could exert a beneficial gastroprotective effect through their antioxidant, anti-inflammatory and anti-apoptotic properties. Furthermore, ECF pre-treatment significantly attenuated the ethanol-induced decrease in CGRP expression, which has a protective role against gastric ulceration. Histopathological examination revealed intact mucosal layer, absence of hemorrhage and necrosis in groups treated with ECF. Ellagitannins were identified as the major active constituents responsible for the marked antioxidant and gastroprotective properties of ECF. The HPLC-PDA-ESI/MS/MS technique was employed to identify the ellagitannins of E. citriodora. PMID:25636864

  15. The Effect of Calcitonin Gene-Related Peptide (CGRP on the Cytosolic Calcium Concentration and Force in Rat Intramural Coronary Arteries

    Directory of Open Access Journals (Sweden)

    M. Sheykhzade

    2001-01-01

    Full Text Available The aim of this study was to investigate the mechanism of CGRP-induced relaxation in intramural rat coronary arteries. By using FURA-2 technique, cytosolic Ca2+-concentration ([Ca2+]i was measured during contraction of the vascular smooth muscle with receptor-dependent agonist (tromboxane A2 analogue U46619 and with high concentration of extracellular potassium. At a steady state of contraction, the increase in [Ca2+]i induced by 300 nM U46619 (100״x 14 nM, n = 7 was similar to that induced by 36 mM K+ (98 ״x 9 nM, n = 7. However, the active tension induced by 300 nM U46619 was significantly (p < 0.01 higher than that induced by 36 mM K+. CGRP concentration-dependently (10 pM - 10 nM reduced both the [Ca2+]i and tension of coronary arteries precontracted with either U46619 or BAY K 8644, and also of resting coronary arteries in PSS. In 36 mM K+-depolarized arteries, CGRP reduced only the tension without affecting the [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with 10 μM thapsigargin significantly (p < 0.05 attenuated the CGRP-induced reduction in the tension (but not [Ca2+]i. In 300 nM U46619 precontracted arteries, pretreatment with either 100 nM charybdotoxin or 100 nM iberiotoxin or 10 nM felodipine significantly (p < 0.05 attenuated the CGRP-induced reduction in both [Ca2+]i and the tension. In contrast, 1 μM glibenclamide did not affect the CGRP-induced responses in these coronary arteries. In resting coronary arteries, only pretreatment with the combination of 1 μM glibenclamide and 100 nM charybdotoxin attenuated the CGRP-induced decrease in the [Ca2+]i and tension, suggesting a different mechanism of action for CGRP in resting coronary arteries. We conclude that CGRP relaxes precontracted rat coronary arteries via three mechanisms: (1 a decrease in [Ca2+]i by inhibiting the Ca2+ influx through membrane hyperpolarization mediated partly by activation of BKCa channels, (2 a decrease in [Ca2+]i presumably by sequestrating cytosolic Ca2+ into thapsigargin-sensitive Ca2+ storage sites, and (3 a decrease in the Ca2+ -sensitivity of the contractile apparatus.

  16. A study on levels of neuropeptide Y, neurotensin motilin and calcitonin gene-reliated peptide in plasma in patients with cerebral infarction and dinical isignificance

    Institute of Scientific and Technical Information of China (English)

    Li Yizhao; Sun Lin; Zhang Dongjun

    2000-01-01

    Objective To explore the relationship between virulent Helicobacter pylori strains infection and cerebral infarction. Method We assessed the prevalence of infection by strains bearing the cytotoxin -associated gene-A(Cag-A),a strong virulence factor ,in 83 patients with cerebral infarction and in 71 age- and sex-matched controls with similar social background. Result Prevalence of Helicobacter pylori infection was significantly higher in patients than in controls(78.3% versus 56.3%,p<0.05),with an odds ratio of 2.8(95%CI,1.46 to 5.36) adjusted for age, sex, main stroke factors. Patients with cerebral infarction also had a higher prevalence of Cag-A-positive strains(45.8% versus 19.7%, P<0.01),with an adjusted odds ratio of 3.43(95%CI 1.5 to 7.24).Conclusion It was suggested that chronic Helicobacter pylori infection, especially Cag-A-positive strains infection is an independent risk factor for cerebral infarction.

  17. 细菌感染及感染程度与血清降钙素原(Procalcitonin PCT)的相关性分析%Bacterial infections and infection degree and serum Procalcitonin of calcitonin original (PCT) correlation analysis

    Institute of Scientific and Technical Information of China (English)

    陈思宇

    2011-01-01

    目的:探讨血清降钙素原(Procalcitonin PCT)与细菌感染的相关性.方法:采用罗氏Cobas E411电化学发光仪测定患者血清PCT含量,比较在不同致病菌感染中PCT含量的差异,以及脓毒症组与非脓毒症组间的差异.结果:以PCT≥0.5ng/ml为阳性阈值,PCT阳性率为88.24%(15/17);而不同致病菌所致感染组间PCT含量无显著性差异(P>0.05);以PCT≥2.0ng/ml为脓毒症的阳性阈值,脓毒症患者与非脓毒症患者血清PCT含量有显著性差异(P<0.01).PCT对脓毒症的临床诊断灵敏度为81.81%(9/11),特异性为100%(6/6).结论:血清PCT是鉴别细菌性感染引发脓毒血症快捷、敏感、准确的监测手段,优于白细胞计数,但不能够判断为何种细菌感染.

  18. Hypercalcémie réfractaire et sécrétion ectopique de calcitonine dans un cancer neuroendocrine du pancréas : Effets hypocalcémiants du Cinacalcet

    OpenAIRE

    Valdes Socin, Hernan Gonzalo; LOLY, Jean-Philippe; BETEA, Daniela; Beckers, Albert; Polus, Marc

    2013-01-01

    Introduction : L’hypercalcémie paranéoplasique est souvent un signe de mauvais pronostic, car elle est particulièrement réfractaire aux traitements hypocalcémiants habituels. Observation : Une tumeur neuroendocrine bien différenciée du pancréas (avec un Ki-67 à 2%) est diagnostiquée chez un homme diabétique de 52 ans. Elle s’associe à une carcinomatose splénique et hépatique, sans métastases osseuses. On note : Calcium 3.54 mmol/L (2.15-2.6), hypophosphatémie, PTH :

  19. 血降钙素原检测在儿科感染性疾病临床诊断中应用分析%Blood calcitonin original detection applied in the pediatric infectious disease clinical diagnosis analysis

    Institute of Scientific and Technical Information of China (English)

    郭建军

    2016-01-01

    目的 分析血清降钙素原检测在儿科感染性疾病临床诊断中的应用.方法 选择2013年7月-2015年1月来我院治疗感染性疾病的儿科患儿180例,经过诊断分成A、B、C三组,A组共有60例患儿为细菌感染组;B组共有60例患儿为病毒性感染组;C组共有60例患儿为非感染组;三组患儿均做血清降钙素原、C-反应蛋白及白细胞计数等检查,研究血降钙素原检测的作用.结果 A组患儿的血清降钙素原及C-反应蛋白阳性率均最高,并且血清降钙素原的检测灵敏度比C-反应蛋白高,B组检测都为阴性,且三组数据差异显著,具有统计学意义(P<0.05).结论 在儿科感染性疾病中采用血清降钙素原检测灵敏度较高,能有效的辅助儿科感染性疾病的诊断,具有较高的临床应用价值.

  20. Application Value of Serum Calcitonin Original in Pediatric Infectious Disease Research%血清降钙素原的检测在儿科感染性疾病中的应用价值研究

    Institute of Scientific and Technical Information of China (English)

    孙淑娜

    2015-01-01

    目的 研究血清降钙素原的检测在儿科感染性疾病中使用价值.方法 选择164例儿科患者,随机分为A、B两组,每组各82例,A组是感染性疾病患者,B组则为同时体检的健康儿童,两组分别展开血清降钙素原检测.结果 检查后A组血清降钙素原阳性率比B组高(P<0.05),且重度感染患者的阳性率比病毒感染患者高(P<0.05),局部感染比病毒感染患者高(P<0.05),有统计学意义.结论 血清降钙素原检测可以对儿科感染性疾病产生重大的积极作用.

  1. The distribution of calcitonin gene-related peptidergic nerve in akin tissue and its significance%CGRP肽能神经在皮肤组织中的分布及其意义

    Institute of Scientific and Technical Information of China (English)

    颜玲; 陈合新; 邵正仁

    2009-01-01

    目的:了解降钙素基因相关肽(caleitonin gene-related peptide,CORP)在皮肤组织中的分布、超微定位,以探讨其在皮肤中功能影响.方法:采用ABC-GND免疫组化染色、免疫透射电镜方法观察CGRP在正常皮肤分布和超微结构情况.结果:CGRP分布在表皮下、毛囊、皮脂腺周围、真皮、皮下以及小血管壁周围,其中以小动脉壁阳性纤维密度大.可见粗、细两种纤维,前者位于真皮深层及皮下,后者位于表皮下、毛囊皮脂腺周围.四肢较胸背皮肤CGRP分布相对多而明显.结论:CGRP可能作为神经调节或神经递质参与皮肤各种生理功能调节.尤其在血管周围分布,可能作为CGRP调节皮肤的机制研究和可能的药物治疗的研究基础.%Objective: To study the distribution ofcalcitonin gene-related peptide (CGRP) nerve fibers in SD rat skin and explore its effects on skin function. Methods: Immunohistochemistry ABC-GND method and immuno-transmission electron microscope were used to explore the distribution of CGRP nerve fibers in SD rat skin tissue and its ultrastructural features. Results: CGRP positive nerve fibers located in epidermis,folliculus,glandulae sebaceae,dermis,cutaneous muscle and small blood vessels,with the highest density in small vessel walls. The CGRP nerve fiber was richer in limbs' skin than that in somatic skin. There were two kinds of CGRP nerve fiber in skin,big fibers,located in the deep layer of dema and epidermis,and fine fibers,in the surrounding of folliculus and glandulae sebaceae. Conclusions: As a kind of neuroregulator,CGRP deal with the physiological functions of skin tissue,which may provide clue for drug treatment of skin diseases.

  2. The effect of 17β-estradiol on gene expression of calcitonin gene-related peptide and some pro-inflammatory mediators in peripheral blood mononuclear cells from patients with pure menstrual migraine

    Directory of Open Access Journals (Sweden)

    Azam Karkhaneh

    2015-09-01

    Results:Treatment with 17β-estradiol had a biphasic effect on expression of CGRP. We found that 17β-estradiol treatment at pharmacological dose significantly increases mRNA expression of CGRP in both groups (P

  3. 血清降钙素及相关指标对肺癌诊治的临床意义%Clinical Significance of Serum Calcitonin and Correlative Tumor Markers in the Diagnosis and Therapy of Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    张爱敏; 张鹏

    2007-01-01

    探讨肺癌患者血清降钙素(CT)含量对肺癌诊治的临床意义.用ELISA检测血清CT含量,用电化学发光免疫分析法(ECLIA)检测血清CEA、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片断(CYFRA 21-1)含量.肺癌患者血清CT含量明显高于对照组,化疗前后比较差别有统计学意义(P<0.01),血清CT阳性率与病理分型无关(P>0.05),与临床分期有关(P<0.01).CT与CEA在肺癌中的阳性表达有差异(P<0.01),与NSE和CYFRA 21-1无差异(P>0.05).血清CT含量动态监测是辅助诊断肺癌、观察疗效和判断预后的重要指标之一.

  4. What People with Lupus Need to Know about Osteoporosis

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  5. What People with Celiac Disease Need to Know about Osteoporosis

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  6. What People with Asthma Need to Know about Osteoporosis

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  7. Osteoporosis and Asian American Women

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  8. Osteoporosis Overview

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  9. Osteoporosis and Hispanic Women

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  10. What People with Inflammatory Bowel Disease Need to Know about Osteoporosis

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  11. What People Recovering from Alcoholism Need to Know about Osteoporosis

    Science.gov (United States)

    ... osteoporosis, including: bisphosphonates; estrogen agonists/antagonists (also called selective estrogen receptor modulators or SERMS); calcitonin; parathyroid hormone; estrogen therapy; hormone ...

  12. LEADER 2

    DEFF Research Database (Denmark)

    Daniels, G H; Hegedüs, L; Marso, S P;

    2015-01-01

    AIMS: To report preliminary data on baseline serum calcitonin concentrations and associated clinical characteristics in a global population with type 2 diabetes before liraglutide or placebo randomization. METHODS: The ongoing LEADER trial has enrolled 9340 people with type 2 diabetes and at high...... with higher serum calcitonin concentrations that were statistically significant. A 20 ml/min/1.73 m(2) decrease in estimated GFR (eGFR) was associated with a 14% increase in serum calcitonin in women and an 11% increase in men. CONCLUSIONS: In the LEADER population, the prevalence of elevated serum calcitonin...

  13. CGRP receptors mediating CGRP-, adrenomedullin- and amylin-induced relaxation in porcine coronary arteries. Characterization with 'Compound 1' (WO98/11128), a non-peptide antagonist

    DEFF Research Database (Denmark)

    Hasbak, P; Sams, A; Schifter, S;

    2001-01-01

    1. Calcitonin gene-related peptide (CGRP), amylin and adrenomedullin (AM) belong to the same family of peptides. Accumulating evidence indicate that the calcitonin (CT) receptor, the CT receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) form the basis of all the recept...

  14. Thyroid and parathyroid gland

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970272 Changes of calcitonin reserve function in pa-tients with primary osteoporosis. ZHAN Zhiwer(詹志伟), et a1. PUMC Hosp, Beijing, 100730. Chin JIntern Med 1997; 36(1): 11-14. Objective: In order to study the role of calcitonin(CT)in osteoporosis. Methods: The calcium loading

  15. Kan isoleret måling af kalcitonin erstatte pentagastrintest?

    DEFF Research Database (Denmark)

    Frohnert, Juliana; Jönsson, Asa Lina; Christiansen, Peer;

    2008-01-01

    INTRODUCTION: Serum calcitonin is used as a tumour marker in patients with medullary thyroid carcinoma. Traditionally, stimulation of calcitonin secretion with pentagastrin has been used. This may, however, cause significant discomfort for the patient. We studied whether measurements of basal...... than the cut-off level in normal subjects after pentagastrin stimulation, but lower before (discrepancy). However, this would have no clinical consequences in any of the cases because serum calcitonin remained measurable, i.e. remnant thyroid tissue had to be present. CONCLUSION: In conclusion, good...

  16. Metastatic medullary thyroid carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Mitra Niafar

    2011-01-01

    Full Text Available Medullary thyroid carcinoma accounts for 4% of thyroid carcinoma and originates from parafollicular cells, secreting calcitonin and carcinoembryonic antigen (CEA. Conventional radiographic modalities such as Computerized Tomography (CT, Magnetic Resonance Imaging (MRI, and Ultrasonography (U/S, are used for detecting recurrences following total thyroidectomy. However, metastatic disease frequently escapes detection by the above modalities, even when its presence is suggested by persistently elevated serum calcitonin levels. In this paper, we report a case of medullary thyroid carcinoma in a 40 year-old woman who had whole body octreotide scintigraphy to evaluate and detect the origin of calcitonin and CEA secretion.

  17. Analysis of the Role of Serum Calcitonin in the Differential Diagnosis of Intracranial Infection in Children%血清降钙素原检测在小儿颅内感染鉴别诊断中的作用分析

    Institute of Scientific and Technical Information of China (English)

    段光敏

    2015-01-01

    目的探究血清降钙素原检测在小儿颅内感染诊断鉴别中的价值,以便为临床提供指导。方法选取细菌性脑膜炎患儿20例作为A组,病毒性脑膜炎患儿20例作为B组,选取体检正常的20例儿童作为正常对照组,检测三组血清钙素原水平。结果 A组血清中降钙素原水平明显高于B组(0.05)。结论血清降钙素原检测在小儿颅内感染诊断鉴别中具有较好的应用价值,确诊率较高。%Objective To explore the diagnostic value of serum procalcitonin in the dif erential diagnosis in children with intracranial infection, in order to provide clinical guidance. Methods 20 cases of bacterial meningitis in children as in group A, 20 cases of viral meningitis in children as group B, select the examination of 20 cases of children as normal control group, the detection of three original serum calcium levels. Results A group of serum procalcitonin levels were significantly higher in group B ( 0.05). Conclusion Serum procalcitonin detection has good application value in dif erential diagnosis in children with intracranial infection, a higher rate of diagnosis.

  18. 血降钙素原在儿童化脓性脑膜炎与病毒性脑膜炎中的鉴别诊断价值%Differential diagnosis value of serum calcitonin level in children with purulent meningitis and viral meningitis

    Institute of Scientific and Technical Information of China (English)

    任磊; 周启立; 刘霞; 祁宏亮; 刘丽娜

    2016-01-01

    Objective To investigate the value of serum procalcitonin (PCT) level in the differential diagnosis of purulent meningitis and viral meningitis in children.Methods Clinical data of 47 children with acute meningitis,admitted to our hospital from January 2013 to January 2015,were analyzed.Among them,21 were purulent meningitis and 26 were viral meningitis.All children accepted tests as cerebrospinal fluid,serum PCT,C-reactive protein (CRP),and erythrocyte sedimentation (ES) inspection;and comparison of results between the two groups was performed.Results The PCT,CRP and ES levels in the purulent meningitis group were (51.96±30.72) μg/L,(182.33±54.49) mag/L,(50.41± 892) mm/h;and those in the viral meningitis group were (0.81 ±0.96) μg/L,(8.87±10.63) mg/L and (16.72±13.20) mm/h;significant differences were noted between the two groups (P<0.05).There were 3 children with viral meningitis having PCT level higher than 0.5 μg/L,while all patients with purulent meningitis having PCT level higher than 0.5 μg/L,enjoying sensitivity and specificity of 100% and 88.46%.There were 8 children with viral meningitis having ES level higher than 20 mm/h,while 19 patients with purulent meningitis having ES level higher than 20 mm/h,enjoying sensitivity and specificity of 90.48% and 69.23%.Area under receiver operating characteristic curve of PCT was 0.982 (95%CI=0.951-1.011),CRP was 0.981 (95%CI=0.952-1.010),without difference.Conclusion PCT has an important diagnostic value in the differential diagnosis of purulent meningitis and viral meningitis in children,which is better than ESR diagnosis.%目的 探讨血降钙素原(PCT)在鉴别诊断儿童化脓性脑膜炎(细菌性脑膜炎)与病毒性脑膜炎中的价值. 方法 收集承德医学院附属医院小儿内科自2013年1月至2015年1月收治的47例急性脑膜炎患儿的临床资料,其中化脓性脑膜炎21例、病毒性脑膜炎26例.所有患儿入院后均接受脑脊液、PCT、C反应蛋白(CRP)、血沉等检查.采用统计学方法对2组患儿各项检查结果进行对比分析. 结果 化脓性脑膜炎组PCT、CRP、血沉水平分别为(51.69±30.72) μg/L、(182.33±54.49) mg/L、(50.41±8.92) mm/h,病毒性脑膜炎组PCT、CRP、血沉水平分别为(0.81 ±0.96) μg/L、(8.87±10.63) mg/L、(16.72±13.20) mm/h,差异均有统计学意义(P<0.05).化脓性脑膜炎组21例患儿PCT水平均>0.5μg/,病毒性脑膜炎组患儿仅有3例PCT水平>0.5 μg/L,敏感性及特异性分别为100%、88.46%.化脓性脑膜炎组有19例患儿血沉水平>20 mm/h,病毒性脑膜炎组患儿仅有8例血沉水平>20 mm/h,敏感性及特异性分别为90.48%、69.23%.受试者工作特征曲线下面积PCT为0.982(95%CI:0.951 ~1.011),CRP为0.981(95%CI:0.952~1.010),差异不大. 结论 PCT在儿童化脓性脑膜炎与病毒性脑膜炎的鉴别诊断中具有重要价值,优于血沉诊断.

  19. Changes of Calcitonin Gene- related Peptide and Glial Cell Line Derived Neurotrophic in Trgeminal Ganglia During Teeth Injury%牙齿损伤后降钙素基因相关肽和胶质源性神经生长因子在三叉神经节中的表达变化

    Institute of Scientific and Technical Information of China (English)

    于静涛; 林莉; 刘纯义

    2001-01-01

    目的:探讨降钙素基因相关肽(CGRP)和胶质源性神经生长因子(GDNF)在大鼠磨牙损伤后不同时段三叉神经节中表达变化.方法:制备大鼠磨牙机械损伤的模型,对其三叉神经节中CGRP和GDNF进行免疫组化染色.结果:在正常三叉神经节中CGRP呈阳性反应,GDNF染色呈阴性;损伤后即刻组CGRP染色阳性,GDNF少许表达;3天组GDNF染色强阳性;损伤5天后CGRP染色强阳性,GDNF表达开始减弱;损伤9天后两者表达恢复到正常水平.结论:CGRP和GDNF参与并促进牙齿损伤后的痛过敏及神经再生修复.

  20. 降钙素受体基因 AluⅠ多态性与绝经后妇女骨密度的关系%Association between the Alu Ⅰ polymorphism in the calcitonin receptor gene and bone mineral density in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    葛继荣; 谢丽华; 陈可; 曾雪爱; 赖玉链; 薛莲

    2010-01-01

    目的 观察降钙素受体基因Alu Ⅰ多态性与绝经后妇女骨密度及骨转换生化标志物的关系.方法 ①2007-01/2008-12从福州常住汉族人中随机检测绝经后妇女623例,均知情同意.②记录年龄、绝经年限、体质量指数和绝经后骨折情况.③双能X线骨密度仪检测正位第2~4腰椎、左侧股骨颈、大转子和Ward's三角区骨密度.④PCR-RFLP技术检测降钙素受体基因Alu Ⅰ多态性.⑤用酶联免疫吸附法检测骨转换生化标志物(血清骨钙素、血清骨碱性磷酸酶、尿吡啶啉和尿脱氧吡啶啉).结果 591例合格受试者进入结果分析,年龄48~84岁,平均62.19±6.32岁.①降钙素受体基因Alu Ⅰ多态性各基因型间骨密度比较差异不显著(P>0.05).②降钙素受体基因Alu Ⅰ多态性各基因型间血清骨钙素、血清骨碱性磷酸酶和尿脱氧吡啶啉比较差异不显著(P>0.05),TT型尿吡啶啉明显低于CC型、TC型,组间比较差异显著(P0.05).④降钙素受体基因Alu Ⅰ多态性各基因型间绝经后骨折比较差异不显著(P>0.05).结论 降钙素受体基因Alu Ⅰ多态性与绝经后骨质疏松症元明显关联,不能作为福州地区绝经后妇女骨质疏松的遗传标记.

  1. The experimental study of calcitonin gene-related peptide intranasal administration to central nervous system and prompt the repair of cerebral infarct%降钙素基因相关肽经鼻给药进入中枢神经系统及促脑梗死修复的实验性研究

    Institute of Scientific and Technical Information of China (English)

    吴庆建; 闫承军; 宋大庆; 刘云海; 孙树印

    2014-01-01

    Objective To develoP a convenient and effective method for delivering CGRP to the central nervous system byPassing the blood-brain barrier( BBB),and to exPlore whether it had Preventive and Protective effects on cerebral in-farction in rats. Methods The MCAO model was made by nylon strand. CGRP concentration was measured IN and IV in-jection of CGRP after 30 min in different brain areas using enzyme-linked immunosorbent assay( ELISA),and exPlored the treatment IN and IV CGRP in rats with focal cerebral infarction. Results CGRP demonstrated a much higher delivery of IN than IV CGRP to the brain regions. Intranasal administration CGRP had significant Preventive and Protective effect to focal cerebral infarction which showed the brain infarction decreased and cerebral blood flow increased( P<0. 01 ). Conclusion CGRP intranasal administration targeting central administration can avoid the blood-brain barrier block,and had Preven-tive and Protective effects on the rats with focal cerebral infarction. Intranasal administration CGRP had definite Preventive and Protective effect to focal cerebral infarction in rats.%目的:寻找快速、便捷有效的靶向中枢给药方法,为脑梗死治疗提供新的思路。方法线栓法制作大鼠大脑中动脉闭塞( Middle cerebral artery occlusion,MCAO)脑缺血再灌注模型,采用ELISA法测定经鼻( IN)和静脉( IV)注射CGRP后30 min时,各脑区的CGRP浓度,并观察IN和IV给予CGRP对局灶性脑梗死的治疗效果。结果 IN给药组脑部各区域、颈髓和脑脊液(Cerebro-sPinal fluid,CSF)中CGRP浓度较IV组显著增高(P<0.01),与IV组相比较,IN给药组梗死体积减小,脑血流量增加( P<0.01)。结论 CGRP经鼻靶向中枢给药可以避开血脑屏障阻碍,并对大鼠局灶性脑梗死有预防和保护作用。

  2. Expression of choline acetyl transferase, dopamine-β-hydroxylase and calcitonin gene related peptide in rats with spinal bifida aperta%显性脊柱裂动物模型膀胱胆碱乙酰转移酶多巴胺β羟化酶和降钙素基因相关肽表达的研究

    Institute of Scientific and Technical Information of China (English)

    杨屹; 李勇; 王常林; 袁正伟

    2005-01-01

    目的显性脊柱裂可导致不同程度的膀胱功能障碍,发病机制不清,该研究旨在探讨胆碱乙酰转移梅(CHAT)、多巴胺β羟化酶(DBH)和降钙素基因相关肽(CGRP)的表达在显性脊柱裂所致神经性膀胱功能障碍发生发发展中的意义.方法用维甲酸(RA)致畸Wistar孕鼠,取20 d显性脊柱裂胎鼠20只.同时取正常胎鼠20只,行苏木精-伊红和免疫组织化学染色,检测胎鼠膀胱CHAT,DBH和CGRP的表达.结果在正常胎鼠,膀胱由粘膜、粘膜下、肌层和外膜组成,CHAT,DBH和CGRP广泛分布于膀胱壁各层,以粘膜层、肌层和外膜细胞胞浆着色明显,表达强度光密度值(OD值)分别为398±13,378±14和412±25.显性脊柱裂胎鼠膀胱壁变薄,肌层发育差,CHAT,DBH,CGRP的表达明显减少,OD值分别为156±9,32±6和121±11,差异具有统计学意义(P<0.01).结论显性脊柱裂胎鼠膀胱壁肌层发育差,膀胱CHAT,DBH,CGRP的表达明显减少,可能是导致显性脊柱裂胎鼠出生后膀胱功能障碍的机制之一.

  3. 鲑鱼降钙素对绝经后骨质疏松性椎体骨折的治疗干预%EFFECTS OF SALMON CALCITONIN ON THE HEALING OF POST-MENOPAUSAL OSTEOPOROSIS AND VERTEBRAE FRACTURES OF THE FEMALE

    Institute of Scientific and Technical Information of China (English)

    钟俊; 刘世清

    2011-01-01

    Objectives: To probe the advangtages of treatment of post-menopausal osteoporosis vertebrae fractures with miacalcic. Methods: 97 patients of post-menopausal osteoporosis vertebrae fractures were selected to investigate the therapeutic effects of Miacalcic and compared with control group. Miacalcic group were treated with injecting Miacalcic 50IU/d on top of routine orthopedic treatment, and patients of control group were only treated with basic orthpaedic treatment. Results: A significant increase in serum bone glaprotein ( BGP) were found in Miacalcic group (t = 3.002, P < 0.01) and a significant decrease in urinary hydroxyproline/creatinine ratio (t = 7.21,P<0.01),as compared to the control after one month of treatment. The average time of fracture healing of Miacalcic group patients were shorter then that of control group. The back pain of Miacalcic group patients disappeared after four weeks of treatment. Conclusions: This study showed that Miacalcic was effective for the treatment of osteoporosis in post-menopausal female and beneficial to the healing of fracture and reducing the back pain.%目的:探讨女性绝经后骨质疏松性椎体骨折的鲑鱼降钙素治疗效果.方法:(1)选择2006年3月至2008年2月武汉大学人民医院骨科女性绝经后骨质疏松性椎体骨折患者97例.患者被随机分为2组:对照组44例,治疗组(鲑鱼降钙素组)53例.(2)两组患者均行卧硬板床、腰背部或胸背部垫软枕,口服钙尔奇D片等治疗.鲑鱼降钙素组在对照组干预措施基础上给予鲑鱼降钙素肌注,50IU/1次/d,连续1个月.(3)分别于治疗前、治疗后1个月采用放射免疫分析法测定血骨钙素、收集晨起第2次尿,偶氮三肿法测定尿钙、化学发光免疫分析法测定尿羟脯氨酸、碱性苦味酸法测定尿肌酐,并计算尿钙/尿肌酐与尿羟脯氨酸/尿肌酐比值.(4)开始治疗后4,6,8周复查脊柱X光正侧位片.了解骨折愈合情况.(5)分别与治疗后2、4周以VAS法评定两组病人背痛缓解情况.结果:纳入患者97例中有2例因肌注密钙息出现面部潮红、头痛、恶心、呕吐、皮肤瘙痒等反应.于用药后3天左右终止治疗,最终进入结果分析95例.(1)所选患者治疗1个月后鲑鱼降钙素组血骨钙素明显高于治疗前(P≤0.01);尿羟脯氨酸/尿肌酐比值明显低于治疗前(P ≤0.01).(2)治疗后4~6周复查X光片示鲑鱼降钙素组骨折愈合率达96.1%,对照组愈合率为79.5%.差异有显著性.(3)鲑鱼降钙素组、对照组分别有28例和17例患者于治疗2周后腰背疼痛消失,分别有43例和27例患者于用药后4周腰背痛消失.结论:鲑鱼降钙素能抑制骨质疏松患者的骨代谢,对骨吸收抑制的作用也很强;鲑鱼降钙素能够促进骨质疏松性椎体骨折的愈合,并能迅速改善腰背痛症状.

  4. 补肾壮骨汤联合鲑鱼降钙素鼻喷剂治疗肾性骨病的临床研究%Clinical Observation of Bushenzhuanggutang Combined with Salmon Calcitonin see Calcimar in the Treatment of Renal Osteopathy

    Institute of Scientific and Technical Information of China (English)

    黎晓辉; 卢叶明; 梁艳萍

    2009-01-01

    目的 探讨补肾壮骨汤联合鲑鱼降钙素鼻喷剂治疗肾性骨病的临床疗效.方法 将48例肾性骨病患者随机分为治疗组与对照组,均予基础治疗,治疗组加用补肾壮骨汤联合鲑鱼降钙素鼻喷剂,对照组加用鲑鱼降钙素鼻喷剂;比较两组临床疗效和血肌酐(Scr)、血尿素氮(BUN)、血清钙、血清甲状旁腺激素(PTH)等指标改善情况.结果 两组治疗后血清磷水平和PTH均较治疗前有不同程度下降,血清钙水平有不同程度升高(P<0.01);临床症状、体征及Scr、BUN均有不同程度的改善(P<0.01);治疗组改善更为明显(P<0.05).结论 补肾壮骨汤联合鲑鱼降钙素鼻喷剂治疗肾性骨病具有更好的临床疗效.

  5. Study of the relationship between gene polymorphism of vitamin D receptor, calcitonin receptor and bone mineral density of the Han nationality woman in Hebei%VDR和CTR基因多态性与河北汉族妇女骨密度关系研究

    Institute of Scientific and Technical Information of China (English)

    许明慧; 刘和娣; 佟晓旭

    2005-01-01

    目的研究维生素D受体(VDR)和降钙素受体(CTR)基因多态性与河北汉族妇女骨密度(BMD)的关系,探讨原发性骨质疏松症(OP)发病的分子机制.方法采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)方法对60名河北汉族妇女的VDR和CTR基因进行多态性分析,比较不同基因型各部位BMD值的差异.结果 VDR Bb基因型者各部位BMD值低于bb型( P<0.05);CTR CC基因型者L1~L4BMD值有较TC基因型者降低趋势(0.05< P<0.1);复合基因型CCBb的BMD值最低.结论 VDR Bb基因型与低值BMD有密切关系;复合基因型CCBb可作为预测中国汉族妇女OP的一项遗传标志.

  6. Headache: Hope through Research

    Science.gov (United States)

    ... head backwards over a sink for hair washing ("beauty parlor stroke"). Immediate medical attention can be lifesaving. ... role of the molecule called calcitonin gene-related peptide (CGRP) in migraines. CGRP is thought to play ...

  7. Procalcitonin Levels Predict Clinical Course and Progression-Free Survival in Patients With Medullary Thyroid Cancer

    NARCIS (Netherlands)

    Walter, Martin A.; Meier, Christian; Radimerski, Tanja; Iten, Fabienne; Kraenzlin, Marius; Mueller-Brand, Jan; de Groot, Jan Willem B.; Kema, Ido P.; Links, Thera P.; Mueller, Beat

    2010-01-01

    BACKGROUND: Procalcitonin has been well established as an important marker of sepsis and systemic infection. The authors evaluated the diagnostic and predictive value of calcitonin and its prohormone procalcitonin in medullary thyroid cancer. METHODS: The authors systematically explored the ability

  8. Long-term tolerability of telcagepant for acute treatment of migraine in a randomized trial

    DEFF Research Database (Denmark)

    Connor, Kathryn M; Aurora, Sheena K; Loeys, Tom;

    2011-01-01

    To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks. Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine....

  9. Insulin resistance and associated dysfunction of resistance vessels and arterial hypertension

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during...

  10. CGRP infusion in unanesthetized rats increases expression of c-Fos in the nucleus tractus solitarius and caudal ventrolateral medulla, but not in the trigeminal nucleus caudalis

    DEFF Research Database (Denmark)

    Bhatt, Deepak K; Ramachandran, Roshni; Christensen, Sarah Louise Tangsgaard;

    2015-01-01

    BACKGROUND AND AIMS: Calcitonin gene-related peptide (CGRP) and glyceryl trinitrate (GTN) infusion in migraineurs provokes headache resembling spontaneous migraine, and CGRP receptor antagonists are effective in the treatment of acute migraine. We hypothesized that CGRP infusion would increase...

  11. The disease modifying osteoarthritis drug (DMOAD): Is it in the horizon?

    DEFF Research Database (Denmark)

    Qvist, Per; Bay-Jensen, Anne-Christine; Christiansen, Claus;

    2008-01-01

    trials, including compounds inhibiting matrix-metalloproteinases (MMPs), bisphosphonates, cytokine blockers, calcitonin, inhibitors of inducible nitric oxide synthase (iNOS), doxycycline, glucosamine, and diacereine. We discuss the challenges associated with the drug development process in general...

  12. Eldercare at Home: Bone Weakness

    Science.gov (United States)

    ... parathyroid hormone, calcitonin, a group of medicines called synthetic estrogen receptor modulators (SERMs), and denosumab. As with ... alternative for those who are intolerant of bisphosphonates. Testosterone replacement for men. Men who have very low ...

  13. 78 FR 2677 - Joint Meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and...

    Science.gov (United States)

    2013-01-14

    ... chance of having a broken bone) outweighs a potential risk of cancer. Calcitonin salmon products approved... are advised that the Agency is not responsible for providing access to electrical outlets....

  14. Somatostatin: a paracrine contribution to hypothyroidism in Hashimoto's thyroiditis.

    OpenAIRE

    Dhillon, A P; Rode, J; Leathem, A; Papadaki, L

    1982-01-01

    Thyroid tissue from 18 consecutive cases of Hashimoto's thyroiditis treated surgically were stained immunohistochemically for neurone specific enolase (NSE), somatostatin, calcitonin and thyroglobulin. Cells staining for NSE and somatostatin were present in 14 cases. In four cases large numbers of cells including oxyphil cells stained for NSE. Consecutive sections showed an identical staining pattern of these cells for somatostatin. Sections stained for calcitonin showed few or no positively ...

  15. Study of Cgrp-Receptors in Human Isolated Middle Meningeal Arteries Using Bibn4096Bs, Compound 1, and HαCgrp(8-37

    Directory of Open Access Journals (Sweden)

    Z. Razzaque

    2001-01-01

    Full Text Available Calcitonin, CGRP, adrenomedullin, and amylin require both CRLR (calcitonin-gene receptor like receptor and receptor activity modifying proteins (RAMP1, RAMP2, and RAMP3 in different combinations for expression of selective, functional receptors[1]. We investigated whether the antagonists BIBN4096BS[2], Compound 1 (WO98/11128, [3], and CGRP(8-37 are functionally selective for CGRP receptors in human middle meningeal arteries (HMMA.

  16. The role of histamine in neurogenic inflammation

    OpenAIRE

    Rosa, A. C.; Fantozzi, R

    2013-01-01

    The term ‘neurogenic inflammation’ has been adopted to describe the local release of inflammatory mediators, such as substance P and calcitonin gene-related peptide, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established. The aim of this review is to...

  17. Relationship between Esophageal Hypersensitivity and Calcitonin Gene-related Peptide Positive Fibers in Lower Esophageal Sphincter Mucosa of Patients with Non-erosive Reflux Disease%非糜烂性反流病患者食管内脏高敏感性与食管下括约肌局部降钙素基因相关肽阳性神经纤维的关系

    Institute of Scientific and Technical Information of China (English)

    杨敏; 房殿春; 李兆申; 徐晓蓉; 邹多武; 孙振兴; 屠振兴; 许国铭; 龚燕芳

    2006-01-01

    背景:食管内脏高敏感性是非糜烂性反流病(NERD)最重要的病理生理特征之一,但引起食管内脏感觉过敏的确切机制仍不甚清楚.目的:通过测定NERD患者食管对机械扩张刺激和对酸刺激的敏感性变化和降钙素基因相关肽(CGRP)在食管下括约肌(LES)局部组织中的表达,探讨食管感知阈值与LES局部黏膜CGRP表达之间的关系.方法:采用Synectics内脏刺激器/电子气压泵行食管气囊扩张术以检测食管对机械扩张刺激的敏感性;采用食管酸灌注试验(bemstein test)检测食管对酸的敏感性;采用免疫组化法和图像分析技术观察LES局部组织中CGRP的表达.结果:根据对酸刺激和(或)机械扩张刺激的感知过敏,NERD患者可分为感知过敏组(21例)和感知正常组(10例).感知过敏组患者食管对气囊扩张刺激的初始感知阈值和最大耐受疼痛阈值较感知正常组和正常对照组显著降低(P<0.05).感觉过敏组LES黏膜中CGRP阳性纤维数和平均吸光度(A)值较感知正常组和正常对照组显著增高(P<0.05).LES局部组织中CGRP阳性产物A值与食管初始感知阈值和最大耐受疼痛阈值呈直线负相关(r分别为-0.68和-0.79,P<0.03).结论:多数NERD患者存在对食管机械扩张刺激和(或)对食管酸刺激感知过敏;感知过敏的NERD患者其LES局部黏膜中CGRP表达增加,提示LES肽能神经的改变可能与食管内脏高敏感性有关.

  18. Osteoclasts Are Required for Hematopoietic Stem and Progenitor Cell Mobilization but Not for Stress Erythropoiesis in Plasmodium chabaudi adami Murine Malaria

    Directory of Open Access Journals (Sweden)

    Hugo Roméro

    2016-01-01

    Full Text Available The anemia and inflammation concurrent with blood stage malaria trigger stress haematopoiesis and erythropoiesis. The activity of osteoclasts seems required for the mobilization of hematopoietic stem and progenitor cells (HSPC from the bone marrow to the periphery. Knowing that BALB/c mice with acute Plasmodium chabaudi adami malaria have profound alterations in bone remodelling cells, we evaluated the extent to which osteoclasts influence their hematopoietic response to infection. For this, mice were treated with osteoclast inhibiting hormone calcitonin prior to parasite inoculation, and infection as well as hematological parameters was studied. In agreement with osteoclast-dependent HSPC mobilization, administration of calcitonin led to milder splenomegaly, reduced numbers of HSPC in the spleen, and their retention in the bone marrow. Although C-terminal telopeptide (CTX levels, indicative of bone resorption, were lower in calcitonin-treated infected mice, they remained comparable in naive and control infected mice. Calcitonin-treated infected mice conveniently responded to anemia but generated less numbers of splenic macrophages and suffered from exacerbated infection; interestingly, calcitonin also decreased the number of macrophages generated in vitro. Globally, our results indicate that although osteoclast-dependent HSC mobilization from bone marrow to spleen is triggered in murine blood stage malaria, this activity is not essential for stress erythropoiesis.

  19. CGRP Receptor Family and Accessory Protein Localization: Implications for Predicted Function

    Directory of Open Access Journals (Sweden)

    K.R. Oliver

    2001-01-01

    Full Text Available Calcitonin gene-related peptide (CGRP, adrenomedullin, amylin, and calcitonin are functionally related neuropeptides. Certain of these peptides mediate their action through receptors which have common components, such as the receptor activity modifying proteins (RAMPs and CGRP-receptor component protein, as well as possibly through other distinct receptors. Specifically, the molecular pharmacology of CGRP and adrenomedullin is determined by coexpression of one of three receptor activity-modifying proteins (RAMPs with calcitonin receptor-like receptor (CRLR. Additionally, through formation of another hetero-oligomer, RAMPs also govern the pharmacology of the calcitonin receptor, which in association with RAMP1 or RAMP3, binds amylin with high affinity. We have used multiple approaches to discern the regional and cellular expression of these various receptor components and binding sites for the above neuropeptides in multiple species and in different tissues. Techniques applied include in situ hybridization, immunohistochemistry and radioligand autoradiography. These data allow further understanding of both the complexity of receptor-receptor component and receptor-ligand interactions in vivo. Interestingly, these localization data suggest that RAMPs may interact with receptors additional to those already identified for the CGRP family and may be involved in binding innate neuropeptides or other neurotransmitters which are not members of the calcitonin gene-related peptide fam

  20. Mixed Medullary-Follicular Carcinoma of the Thyroid

    Directory of Open Access Journals (Sweden)

    Maasumeh Tohidi

    2013-01-01

    Full Text Available Introduction. Mixed medullary-follicular thyroid carcinoma is an uncommon tumor that consists of both follicular and parafollicular cells. Case. We report a 43-year-old woman with a palpable mass in the right side of the neck. Fine needle aspiration suggested a diagnosis of high grade anaplastic carcinoma that has been associated with papillary features. Total thyroidectomy was done in which histopathological examination showed diagnosis of medullary carcinoma. Immunohistochemical staining was positive for chromogranin, calcitonin, and thyroglobulin in tumoral cells. Conclusion. Mixed medullary-follicular thyroid carcinoma is a rare tumor. Diagnosis of these tumors with fine needle aspiration is very difficult and may lead to misdiagnosis. It is necessary to correlate the cytological finding with serum calcitonin and thyroglobulin. Also immunostaining for calcitonin and thyroglobulin confirms diagnosis.

  1. The immunohistochemical demonstration of parafollicular cells and evaluation of calcium-phosphate balance in patients with thyroid hemiagenesis

    Directory of Open Access Journals (Sweden)

    Jerzy Sowinski

    2011-07-01

    Full Text Available Thyroid hemiagenesis (TH is characterized by the congenital absence of one thyroid lobe. The aim of this study was to evaluate the calcium-phosphate balance in TH. Twenty patients with TH and 20 controls with a bilobed thyroid were studied. Serum concentrations of total calcium, parathormon and calcitonin were measured. Additionally, the immunohistochemical expression of calcitonin, chromogranin A (chA, neuron-specific enolase (NSE and calcitonin gene-related peptide (CGRP was evaluated in surgical specimens from patients with TH and controls. There were no significant differences in biochemical parameters between TH and controls. Positive staining for calcitonin was demonstrated in 3/8 thyroid sections from three patients with TH, but only in 2/33 sections from four controls (p < 0.005. All sections from patients with TH positive for calcitonin also expressed chA, NSE and CGRP. Two sections from controls positive for calcitonin presented an additionally positive reaction for chA, and one of them also for NSE. None presented positive staining for CGRP. Of three TH sections, in one, hyperplasia of C cells of medium grade, and in another hyperplasia of C cells of high grade, could be detected. In the controls, hyperplasia of C cells of low and medium grade was observed. TH was associated with slightly enhanced C cells hyperplasia compared to controls, which might indicate compensatory proliferation. However, the calcium-phosphate balance does not seem to be significantly affected. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 299–305

  2. Radioisotope studies in algodystrophic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    De Rossi, G.; Focacci, C.; Salvatori, M.; Regi, M.; Bertolini, C.; Piazzini, D.; Sterzi, S.; Greco, F.

    1983-10-01

    A total of 22 patients with algodystrophic syndrome was studied, treated with calcitonin (n = 11) or magnetotherapy (n = 11). Scintigraphy was performed before and 3 months after the onset of therapy. The ratio between the counts on the pathologic segment (P) vs. a contralateral normal area (N) was calculated. Pre-/posttherapy P/N difference was found to correlate well with clinical improvement. On the basis of such a follow-up method calcitonin treatment seemed to achieve better results than magnetotherapy, at least in the first clinical stadium of the disease.

  3. CGRP receptor antagonist olcegepant (BIBN4096BS) does not prevent glyceryl trinitrate-induced migraine

    DEFF Research Database (Denmark)

    Tvedskov, Jesper Filtenborg; Tfelt-Hansen, P; Petersen, K A;

    2010-01-01

    There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN.......There is a striking similarity between the migraine-provoking effect of the nitric oxide (NO) donor glyceryl trinitrate (GTN) and that of calcitonin gene-related peptide (CGRP). We tested the hypothesis that NO releases CGRP to cause the delayed migraine attack after GTN....

  4. Strontium is a biased agonist of the calcium-sensing receptor in rat medullary thyroid carcinoma 6-23 cells

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Worm, Jesper; Jacobsen, Stine Engesgaard;

    2012-01-01

    SR agonists, calcium and strontium, to activate six different signaling entities: G(q/11) signaling, G(i/o) signaling, G(s) signaling, extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling, intracellular calcium ([Ca(2+)](i)) mobilization, and calcitonin secretion. The experiments showed...... that strontium biases CaSR signaling toward ERK1/2 signaling and possibly another pathway independent of G(q/11) signaling and [Ca(2+)](i) mobilization. It is noteworthy that the potency of strontium-stimulated calcitonin secretion was elevated compared with calcium. Combining these results with experiments...

  5. Insulin-like growth factors I and II in healthy women with and without established osteoporosis

    DEFF Research Database (Denmark)

    Ravn, Pernille; Spencer, E M; Christiansen, C

    1995-01-01

    -controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p < 0.001) as compared to women above that age. For women more than 35 years of age, we found no...

  6. Effect of two novel CGRP-binding compounds in a closed cranial window rat model

    DEFF Research Database (Denmark)

    Juhl, Louise Kathrine; Edvinsson, Lars; Olesen, Jes;

    2007-01-01

    We investigated the in vivo effects of two novel calcitonin gene-related peptide (CGRP) binding molecules in the genuine closed cranial window model in the rat. The RNA-Spiegelmer (NOX-C89) and the monoclonal CGRP antibody are CGRP scavengers and might be used as an alternative to CGRP-receptor a...

  7. Malignant osteopetrosis: hypercalcaemia after bone marrow transplantation.

    OpenAIRE

    Rawlinson, P S; Green, R H; Coggins, A M; Boyle, I T; Gibson, B.E.

    1991-01-01

    A 3 year old girl presented with malignant osteopetrosis, which was treated by allogeneic bone marrow transplantation. Successful engraftment was complicated by prolonged hypercalcaemia, which was controlled by a combination of a bisphosphonate, phosphate infusions, vigorous resalination, and salmon calcitonin. She was alive and well 16 months after the transplant.

  8. Role of Ser102 and Ser104 as Regulators of cGMP Hydrolysis by PDE5A

    DEFF Research Database (Denmark)

    Carøe Nordgaard, Julie; Kruse, Lars Schack; Gammeltoft, Steen;

    2014-01-01

    -N-AS neuroblastoma cells as C-terminal fusions with green fluorescent protein. Transfected cells were treated with sildenafil, cilostazol, glyceryl trinitrate, calcitonin gene-related peptide (CGRP) or sumatriptan. PDE5A-GFP fusion proteins were localized in fixed cells by immunofluorescence and PDE activity...

  9. Thyroid nodule guidelines: agreement, disagreement and need for future research

    DEFF Research Database (Denmark)

    Paschke, Ralf; Hegedüs, Laszlo; Alexander, Erik;

    2011-01-01

    countries. Most of the discordance, for example, on the use of calcitonin screening or fine-needle aspiration cytology classification, could probably be resolved by further expert discussions, as the basis is the same published evidence. Importantly, owing to a current lack of evidence in many areas...

  10. Domain Modeling: NP_001732.1 [SAHG[Archive

    Lifescience Database Archive (English)

    Full Text Available NP_001732.1 chr11 Solution Conformation of A Non-Amyloidogenic Analogue of Human Ca...lcitonin in Sodium Dodecyl Sulfate Micelles p2jxza_ chr11/NP_001732.1/NP_001732.1_holo_85-117.pdb blast 108Q,115A,116P,117G NH2 0 ...

  11. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine

    DEFF Research Database (Denmark)

    Bigal, Marcelo E; Edvinsson, Lars; Rapoport, Alan M;

    2015-01-01

    BACKGROUND: Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine. METHODS: In t...

  12. The headache-inducing effect of cilostazol in human volunteers

    DEFF Research Database (Denmark)

    Birk, S; Kruuse, Christina; Petersen, K.A.;

    2006-01-01

    We have previously shown that nitric oxide (NO) and cyclic guanosine monophosphate (GMP) may cause headache and migraine. However, not all findings in previous studies can be explained by an activation of the NO-cGMP pathway. Calcitonin gene-related peptide (CGRP) causes headache and migraine in ...

  13. Circulating levels of vasoactive peptides in patients with acute bacterial meningitis

    DEFF Research Database (Denmark)

    Berg, Ronan Martin Griffen; Strauss, Gitte Irene; Tofteng, Flemming;

    2009-01-01

    PURPOSE: The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all...

  14. Headache after exposure to ‘date-rape’ drugs

    OpenAIRE

    Peatfield, Richard; Villalón, Carlos M

    2013-01-01

    Summary We report two patients who developed a prolonged featureless headache, they think after a drink was ‘spiked’. We speculate that each was exposed to scopolamine, resulting in enhanced trigeminal release of vasodilator neuropeptides, including Calcitonin Gene-Related Peptide (CGRP), and thus the headache.

  15. K(ATP) channel openers in the trigeminovascular system

    DEFF Research Database (Denmark)

    Ploug, K B; Amrutkar, D V; Baun, M;

    2012-01-01

    The ATP-sensitive K(+) (K(ATP)) channel openers levcromakalim and pinacidil are vasodilators that induce headache in healthy people. The neuropeptide calcitonin gene-related peptide (CGRP) induces headache in healthy people and migraine in migraineurs, potentially through a mechanism that involve...

  16. Driveline infections in patients supported with a HeartMate II: Incidence, aetiology and outcome

    DEFF Research Database (Denmark)

    Bomholt, Tobias Peter Zwergius; Moser, Claus; Sander, Kaare;

    2011-01-01

    sensitivity of 27% and C-reactive protein (CRP) a sensitivity of 28%. In 22 cases of driveline infections plasma pro-calcitonin was found to be normal. Conclusion. Driveline infections are common in HMII recipients but primarily remain superficial and are reasonably easy to manage. Infectious agents mostly...

  17. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention

    DEFF Research Database (Denmark)

    Ho, Tony W; Connor, Kathryn M; Zhang, Ying;

    2014-01-01

    OBJECTIVE: To evaluate whether the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant might be effective for migraine prevention. METHODS: In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3-14 migra...

  18. Randomized, controlled trial of telcagepant over four migraine attacks

    DEFF Research Database (Denmark)

    Ho, Andrew P; Dahlöf, Carl Gh; Silberstein, Stephen D;

    2010-01-01

    This study evaluated the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant (tablet formulation) for treatment of a migraine attack and across four attacks. Adults with migraine were randomized, double-blind, to telcagepant 140 mg, telcagepant 280 mg, or control treatment sequ...

  19. Excellent tolerability but relatively low initial clinical efficacy of telcagepant in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer

    2011-01-01

    In 3 randomized clinical trials (n = 1585) the calcitonin gene-related peptide antagonist telcagepant 300 mg orally had an incidence of adverse events similar to placebo when used in the acute treatment of migraine. Telcagepant, thus, has excellent tolerability in migraine. Only a quarter (26%) (...

  20. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

    The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. Both are effective in migraine but in doses much higher than would be predicted from receptor binding and other in vitro results. This could perhaps suggest an effect of CGRP antagoni...

  1. Drug: D09392 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 09392.gif Treatment of migraine calcitonin receptor-like (CALCRL) antagonist [HSA:10203] [KO:K04577] hsa0408...D09392 Drug Telcagepant potassium (USAN) C26H26F5N6O3. C2H6O. K 650.2042 650.6818 D

  2. Neuronal signal substances as biomarkers of migraine

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2006-01-01

    Of the sensory nervous system associated signal substances it is only calcitonin generelated peptide (CGRP) that is reliably associated with the degree of pain in the acute attacks of primary headaches. The treatment with triptans alleviates both the pain and the associated CGRP release, putative...

  3. Importance of a proper placement for your data point

    Institute of Scientific and Technical Information of China (English)

    Zong-Jie Cui

    2004-01-01

    @@ To the Editor: I read the work by Hang et al.[1] with much interest. This might have been a very important paper, which investigated the effects of traumatic brain injury on the levels of brain-gut hormone vasoactive intestinal peptide (VIP), cholecystokinin (CCK), and calcitonin gene-related peptide (CGRP) both in plasma and in jejunum in rats.

  4. DRAFT: Russian Association of Endocrinologists Clinic Guidelines for Thyroid Nodules Diagnostic and Treatment

    Directory of Open Access Journals (Sweden)

    Vladimir Eduardovich Vanushko

    2015-05-01

    Full Text Available Russian guidelines for diagnostic of thyroid nodules gained some actual questions: necessity of ultrasound (US-screening of the thyroid cancer, indications for fine needle aspiration and exam of calcitonin, necessity of unification of US and cytopathology classification for signs of thyroid nodules. 

  5. A second trigeminal CGRP receptor

    DEFF Research Database (Denmark)

    Walker, Christopher S; Eftekhari, Sajedeh; Bower, Rebekah L;

    2015-01-01

    OBJECTIVE: The trigeminovascular system plays a central role in migraine, a condition in need of new treatments. The neuropeptide, calcitonin gene-related peptide (CGRP), is proposed as causative in migraine and is the subject of intensive drug discovery efforts. This study explores the expressio...

  6. Improvement of the closed cranial window model in rats by intracarotid infusion of signalling molecules implicated in migraine

    DEFF Research Database (Denmark)

    Gupta, S; Bhatt, D K; Boni, L J;

    2010-01-01

    Intravital microscopy on a closed cranial window allows one to measure change in the diameter of cranial blood vessels after intravenous (i.v.) administration of pharmacodynamic substances. Putative targets being pursued in migraine are large vasodilating peptide molecules such as calcitonin gene...

  7. NXN-188, a selective nNOS inhibitor and a 5-HT1B/1D receptor agonist, inhibits CGRP release in preclinical migraine models

    DEFF Research Database (Denmark)

    Bhatt, Deepak K; Gupta, Saurabh; Jansen-Olesen, Inger;

    2013-01-01

    BackgroundNXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptor agonist. Using preclinical models, we evaluated whether these two unique therapeutic principles have a synergistic effect in attenuating stimulated calcitonin gene-...

  8. Studies on Treating Eczema by Chinese Herbal Medicine with Anti-Type

    Institute of Scientific and Technical Information of China (English)

    LIN; Xi-ran

    2001-01-01

    [1]ZHAO B. Clinical dermatology. 2nd Edition. Nanjing: Jiangsu Science and Technology Press, 1989∶512, 114-116, 513-515.[2]Lorens EK, Elvar T. Tachykinin and calcitonin gene-related peptide in oxazolone induced allergic contact dermatitis in mice. J Invest Dermatol 1990;94∶761-767.

  9. A pathophysiological view of primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2000-01-01

    The cerebral circulation is innervated by sympathetic, parasympathetic and sensory nerves which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide (CGRP...... normalised. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches....

  10. Pathophysiology of primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2001-01-01

    The cerebral circulation is innervated by sympathetic, parasympathetic, and sensory nerves, which store a considerable number of neurotransmitters. The role of these has been evaluated in primary headaches. A clear association between head pain and the release of calcitonin gene-related peptide...... normalized. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches....

  11. Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Edvinsson, Lars; Larsen, Fin Stolze;

    2001-01-01

    The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant...

  12. Neuropeptides in the seminal vesicles, locations, binding sites and functional implications

    OpenAIRE

    M. S. Pinho; Afonso, F.; Rodriguez, G.; Gulbenkian, S; Mata, L.R.

    1997-01-01

    The importance of neurona1 factors in the normal physiology of the seminal vesicles has been traditionally underestimated when compared to the trophic role of androgens. Immunohistochemical, autoradiographical and pharmacological experiments have, however, raised the possibility that neuropeptides, such as vasoactive intestinal polypeptide (VIP), neuropeptide tyrosine (NPY) and calcitonin gene-related peptide (CGRP), are necessary for full seminal vesicle f...

  13. Interstitial cells of Cajal in the striated musculature of the mouse esophagus

    DEFF Research Database (Denmark)

    Rumessen, J J; de Kerchove d'Exaerde, A; Mignon, S;

    2001-01-01

    fibers immunoreactive for neuronal nitric oxide synthase (nNOS), vasoactive intestinal polypeptide (VIP) or neuropeptide Y (NPY), but not to fibers immunoreactive for substance P (SP), calcitonin gene related peptide (CGRP), enkephalin, or the capsaicin receptor VRI. They were present in the fetus...

  14. Peptidergic and non-peptidergic innervation and vasomotor responses of human lenticulostriate and posterior cerebral arteries

    DEFF Research Database (Denmark)

    Jansen-Olesen, Inger; Gulbenkian, Sergio; Engel, Ulla;

    2004-01-01

    immunoreactivity for tyrosine hydroxylase (TH) and neuropeptide Y (NPY). Only few nerve fibers displayed vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity. In both arteries, the contractions induced by noradrenaline (NA), NPY and 5...

  15. Investigation of CGRP receptors and peptide pharmacology in human coronary arteries. Characterization with a nonpeptide antagonist

    DEFF Research Database (Denmark)

    Hasbak, Philip; Saetrum Opgaard, Ole; Eskesen, Karen;

    2003-01-01

    Calcitonin gene-related peptide (CGRP), adrenomedullin (AM), and amylin are structurally related peptides mediating vasorelaxation in the coronary circulation possibly via CGRP receptors (subtypes 1 or 2). Functional CGRP1 receptors appear to consist of at least three different kinds of proteins:...

  16. Diagnosis of medullary thyroid cancer and prognostic factors of disease aggressiveness

    Directory of Open Access Journals (Sweden)

    D O Gazizova

    2013-12-01

    Full Text Available In the study were enrolled 137 patients with medullary thyroid cancer (MTC. Low 35%-sensitivity of FNAC and high accuracy of basal calcitonin in MTC diagnostics were found. Mutation analysis of the RET pro- tooncogene in familial and sporadic MTC, RAS -gene in sporadic MTC were done. The correlation between type of the mutation and disease aggressiveness was found.

  17. Effect of oxygen inhalation on systemic, central, and splanchnic haemodynamics in cirrhosis

    DEFF Research Database (Denmark)

    Møller, S; Becker, U; Schifter, S;

    1996-01-01

    catecholamines, renin, endothelin-1, and calcitonin gene-related peptide were all increased in patients with cirrhosis, but only the catecholamine concentrations decreased significantly (noradrenaline -13%, p < 0.02 and adrenaline -16%, p < 0.01) in response to oxygen. CONCLUSION: During oxygen inhalation...

  18. Characterization of CGRP(1) receptors in the guinea pig basilar artery

    DEFF Research Database (Denmark)

    Jansen-Olesen, I; Kaarill, L; Edvinsson, L

    2001-01-01

    The purpose of the present study was to characterise receptors mediating calcitonin gene-related peptide (CGRP)-induced relaxation of guinea pig basilar artery. This was done by investigating vasomotor responses in vitro and performing autoradiographic binding studies. We also intended to study t...

  19. Is thyroidectomy necessary in RET mutations carriers of the familial medullary thyroid carcinoma syndrome?

    DEFF Research Database (Denmark)

    Hansen, H S; Torring, H; Godballe, C;

    2000-01-01

    BACKGROUND: The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS: In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary th...

  20. Enhanced expression of CGRP in rat trigeminal ganglion neurons during cell and organ culture

    DEFF Research Database (Denmark)

    Kuris, Anikó; Xu, Cang-Bao; Zhou, Ming Fang;

    2007-01-01

    The sensory innervation of intracranial vessels originates in the trigeminal ganglion with calcitonin gene-related peptide (CGRP), substance P (SP) and pituitary adenylate cyclase activating peptide (PACAP) as frequent neuronal messengers. The present study was designed to study the expression of...

  1. Leaf Disk Transformation of Lactuca sativa Using Agrobacterium tumefaciens

    Directory of Open Access Journals (Sweden)

    Sergiu VALIMAREANU

    2010-12-01

    Full Text Available Reliable methods of transferring cloned genes into plants are essential for engineering crops with desired traits. In order to induce sap-sucking insect resistance Agrobacterium tumefaciens LBA 4404 (1065 strain containing the binary vector pMOG 23 and hypervirulent pTOK 47 plasmid was used. pta (Pinellia ternata agglutinin, salmon ct (calcitonin and cgrp (calcitonin gene related protein genes were successfully integrated into Lactuca sativa plants. This genetic modification conferred lettuce resistance to orthopteran and homopteran insects like Nilaparvata lugens Stl or Myzus persicae Sulzer. Lactuca sativa could be routinely transformed using Ti plasmids of A. tumefaciens containing a chimeric kanamycin resistance gene (nos nptII. nos.

  2. Changes of serum PTH and CT levels in hyperthyroidism and hypothyroidism

    International Nuclear Information System (INIS)

    Objective: To explore the serum level changes of parathyroid hormone (PTH) and Calcitonin (CT) in hyperthyroid-and hypothyroid-patients. Methods: Serum parathyroid hormone and Calcitonin levels were determined With RIA in 62 cases of hyperthyroidism, 32 cases of hypothyroidism and 35 normal Controls. Results: The serum PTH levels in patients with hyperthyroidism were lower than those in controls (P < 0.05); the PTH levels in patients with hypothyroidism were high than normal (P < 0.01). The serum CT levels were decreased both in hyperthyroid and hypothyroid patients (P < 0.01). Conclusion: Determination of changes of serum PTH and CT levels in hyperthyroidism and hypothyroidism was of important clinical Significance

  3. Surgery for lymph node metastases of medullary thyroid carcinoma: A review.

    Science.gov (United States)

    Jin, Linda X; Moley, Jeffrey F

    2016-02-01

    Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A "berry-picking" approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease. PMID:26539937

  4. The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

    Science.gov (United States)

    Woolley, Michael. J.; Watkins, Harriet A.; Taddese, Bruck; Karakullukcu, Z. Gamze; Barwell, James; Smith, Kevin J.; Hay, Debbie L.; Poyner, David R.; Reynolds, Christopher A.; Conner, Alex C.

    2013-01-01

    The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed. PMID:24047872

  5. The vasorelaxant effect of adrenomedullin, proadrenomedullin N-terminal 20 peptide and amylin in human skin

    DEFF Research Database (Denmark)

    Hasbak, Philip; Eskesen, Karen; Lind, Peter Henrik;

    2006-01-01

    of the peptides. The mRNA expression was assessed by real-time reverse transcriptase-polymerase chain reaction (real-time PCR). CGRP, adrenomedullin and amylin induced concentration-dependent, long-lasting increases in skin blood flow. The response to PAMP was shorter in duration appearing similar......In this study we aimed to assess in vivo, the vasodilator effects of adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP) and amylin in human skin vasculature and compare the responses to the effects mediated by the endogenous neuropeptides calcitonin gene-related peptide (CGRP......) and substance P and to examine the mRNA expression of calcitonin receptor-like receptor (CL-R) and receptor-activity modifying proteins, RAMP1, RAMP 2 and RAMP3 in human subcutaneous arteries. Changes in skin blood flow of the forearm were measured using a Laser Doppler Imager after intradermal injection...

  6. Neurochemical mechanism of the gastrointestinal interdigestive migrating motor complex in rats with acute inflammatory stomach ache

    Institute of Scientific and Technical Information of China (English)

    Xiaoli Xu; Qin Li; Lv Zhou; Liqiang Ru

    2012-01-01

    The normal gastrointestinal interdigestive migrating motor complex cycle was interrupted, and paroxysmal contraction appeared after formaldehyde-induced stomach ache. Activities of nitric oxide synthase, acetylcholinesterase and vasoactive intestinal peptide neurons were significantly reduced, whereas activities of calcitonin gene-related peptide neurons were significantly increased in the pyloric sphincter muscular layer, myenteric nerve plexus and submucous nerve plexus. Electroacupuncture at Zusanli (ST36) suppressed paroxysmal contraction in rats with formaldehyde-induced stomach ache, and neurons in the enteric nervous system were normal. These results indicated that nitrergic neurons, cholinergic neurons, vasoactive intestinal peptide neurons and calcitonin gene-related peptide neurons in the enteric nervous system may be involved in changes to the gastrointestinal interdigestive migrating motor complex following stomach ache, and that electroacupuncture can regulate this process.

  7. Immunocytochemical localization and identification of prosomatostatin gene products in medullary carcinoma of human thyroid gland.

    Science.gov (United States)

    Scopsi, L; Ferrari, C; Pilotti, S; Holst, J J; Rehfeld, J F; Fossati, G; Rilke, F

    1990-08-01

    Thirty-three cases of histologically proven calcitonin-positive medullary thyroid carcinoma were studied immunocytochemically for the occurrence of prosomatostatin-related peptides. Positive cells, identified with a panel of antisera raised against four different regions of the prosomatostatin molecule, were found in 100% of the tumors. Most but not all somatostatin-positive cells were also immunoreactive for calcitonin. Notably, seven patients harboring somatostatin-rich tumors revealed a more favorable clinical course. The results (1) indicate that somatostatin production is a universal concomitant of thyroid medullary carcinoma, (2) suggest that these cells are likely to produce a somatostatin precursor molecule similar to mammalian prosomatostatin, and (3) imply that somatostatin-reactive cells may have as yet unknown roles in these tumors, possibly in the realm of paracrine and autocrine regulation of cell growth.

  8. Immunocytochemical localization and identification of members of the pancreatic polypeptide (PP)-fold family in human thyroid C cells and medullary carcinomas.

    Science.gov (United States)

    Scopsi, L; Pilotti, S; Rilke, F

    1990-09-10

    An increasing number of regulatory peptides not coded by the calcitonin genes are known to occur in the thyroid C cells. We have now carried out light and electron microscopic immunocytochemical analyses on specimens of normal human thyroids and medullary carcinomas to establish the occurrence of members of the PP-PYY-NPY family in the C cell system. By means of site-directed immunocytochemistry we provide the first evidence that a molecule closely related to proNPY is present in normal and pathologic C cells, and is co-stored with calcitonin in the cytoplasmic dense-core granules. Preliminary observations also suggest that high levels of expression of NPY-gene products help to define a subset of tumours with a less aggressive behaviour.

  9. Peptide-evoked release of amylase from isolated acini of the rat parotid gland

    DEFF Research Database (Denmark)

    Goll, R; Poulsen, J H; Schmidt, P;

    1994-01-01

    Investigations of the effects of the neuropeptides, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK), gastrin releasing peptide (GRP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP), and of acetylcholine on amylase secretion have been carried out on isola......Investigations of the effects of the neuropeptides, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK), gastrin releasing peptide (GRP), calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP), and of acetylcholine on amylase secretion have been carried out...... amylase release. VIP, however, with a rather low potency (EC50 at 155 nmol/l). Simultaneous stimulation with two compounds elicited additive responses, except for VIP and acetylcholine which elicited an effect significantly above additive response. Only SP, NKA, VIP and CGRP could be identified...... of NK1-receptors. Thus, the results of the present study support previous suggestions that the tachykinins and VIP are likely to be involved in amylase secretion in the rat parotid gland....

  10. The Relationship Between Cytokine Regulation and Anti-Inflammatory Action of Amine-Carboxyborane in L929 Fibroblasts and IC-21 Macrophages

    OpenAIRE

    Murphy, Margaret E.; Shrewsbury, Robert P.; Sood, Anup; Spielvogel, Bernard F.; Elkins, Amy L.; Hall, Iris

    1995-01-01

    The amine-carboxyboranes anti-inflammatory agents were shown to block TNFα release at 90 min. and IL-1 release at 5 hr. from macrophages. The agenst competed with L929 fibroblasts high affinity receptors for endogenous cytokines which regulate the inflammation process. Blocking the TNFα receptor at 90 min. by the agents from 10 to 50  μΜ , resulted in lysosomal hydrolytic enzyme inhibition and lowering of prostaglandin synthesis as well as reductions in calcitonin high affinity receptor bindi...

  11. Understanding migraine: Potential role of neurogenic inflammation

    OpenAIRE

    Rakesh Malhotra

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripher...

  12. Amplified Mechanically Gated Currents in Distinct Subsets of Myelinated Sensory Neurons following In Vivo Inflammation of Skin and Muscle

    OpenAIRE

    Weyer, Andy D.; O'Hara, Crystal L.; Cheryl L Stucky

    2015-01-01

    Primary afferents are sensitized to mechanical stimuli following in vivo inflammation, but whether sensitization of mechanically gated ion channels contributes to this phenomenon is unknown. Here we identified two populations of murine A fiber-type sensory neurons that display markedly different responses to focal mechanical stimuli of the membrane based on their expression of calcitonin gene-related peptide (CGRP). Following inflammation of the hindpaw, myelinated, CGRP-positive neurons proj...

  13. An immunohistochemical study of the pulpal nerve supply in primary human teeth: evidence for the innervation of deciduous dentine.

    OpenAIRE

    Egan, C A; Bishop, M A; Hector, M P

    1996-01-01

    The innervation of pulp and dentine was studied in fully formed human deciduous teeth using antibodies to calcitonin gene related peptide (CGRP). Freshly extracted healthy teeth were divided, fixed, demineralised, cryosectioned and treated with antibodies to human CGRP which was then labelled with horseradish peroxidase. Bundles of nerve fibres passed from the apex of the root to the coronal region where a subodontoblast plexus was formed. In the cervical half of the root some nerve fibres br...

  14. Introduction to Peptide Synthesis

    OpenAIRE

    Stawikowski, Maciej; Fields, Gregg B.

    2002-01-01

    A number of synthetic peptides are significant commercial or pharmaceutical products, ranging from the dipeptide sugar-substitute aspartame to clinically used hormones, such as oxytocin, adrenocorticotropic hormone, and calcitonin. This unit provides an overview of the field of synthetic peptides and proteins. It discusses selecting the solid support and common coupling reagents. Additional information is provided regarding common side reactions and synthesizing modified residues.

  15. TWO TYPES OF NEUROTRANSMITTER RELEASE PATTERNS IN IB4-POSITIVE AND NEGATIVE TRIGEMINAL GANGLION NEURONS

    OpenAIRE

    Matsuka, Yoshizo; Edmonds, Brian; Mitrirattanakul, Somsak; Schweizer, Felix E.; Spigelman, Igor

    2006-01-01

    Mammalian nociceptors have been classified into subclasses based on differential neurotrophin sensitivity and binding of the plant isolectin B4 (IB4). Most of the nerve growth factor-responsive IB4-negative (IB4 (-)) nociceptors contain neuropeptides such as substance P and calcitonin gene-related peptide, whereas the glial-derived neurotrophic factor-responsive IB4-positive (IB4 (+)) neurons predominantly lack such neuropeptides. We hypothesized that the differences in neuropeptide content b...

  16. Role of serum procalcitonin level in early diagnosis of bacterial pneumonia in children, a hospital based study

    OpenAIRE

    Sheikh Mohd Saleem; S. M. Salim Khan; Shah Sumaya Jan

    2016-01-01

    Background: Procalcitonin (PCT) is a precursor of hormone calcitonin. It is composed of 116 amino acids and is produced by para follicular C cells of the thyroid and by neuroendocrine cells of lungs and intestine. The level of Procalcitonin in healthy individuals is below the limit of detection (0.01 and micro;g/L).These levels may rise from extra thyroid tissues especially in response to inflammatory stimulus of bacterial origin. PCT has the greatest sensitivity and Specificity for different...

  17. Essential Roles of Enteric Neuronal Serotonin in Gastrointestinal Motility and the Development/Survival of Enteric Dopaminergic Neurons

    OpenAIRE

    Li, Zhishan; Chalazonitis, Alcmène; Huang, Yung-Yu; Mann, J. John; Margolis, Kara Gross; Yang, Qi Melissa; Kim, Dolly O.; Côté, Francine; Mallet, Jacques; Gershon, Michael D.

    2011-01-01

    The gut contains a large 5-HT pool in enterochromaffin (EC) cells and a smaller 5-HT pool in the enteric nervous system (ENS). During development, enteric neurons are generated asynchronously. We tested hypotheses that serotonergic neurons, which arise early, affect development/survival of later-born dopaminergic, GABAergic, nitrergic, and calcitonin gene-related peptide-expressing neurons and are essential for gastrointestinal motility. 5-HT biosynthesis depends on tryptophan hydroxylase 1 (...

  18. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia

    OpenAIRE

    Roman, Carolyn W.; Derkach, Victor A.; Palmiter, Richard D

    2016-01-01

    The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRPPBN) neuron...

  19. Pathophysiological study of diarrhoea in a patient with medullary thyroid carcinoma. Evidence against a secretory mechanism and for the role of shortened colonic transit time.

    OpenAIRE

    Rambaud, J C; Jian, R; Flourié, B; Hautefeuille, M; Salmeron, M.; Thuillier, F.; Ruskoné, A; Florent, C; F. Chaoui; BERNIER, J.J.

    1988-01-01

    Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2 alpha. Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and...

  20. Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

    OpenAIRE

    2015-01-01

    Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can res...

  1. Extrapulmonary small cell gastric carcinoma. A case report and review of the literature

    International Nuclear Information System (INIS)

    The described case of small cell gastric carcinoma, limited in stage at the time of diagnosis, had an excellent response to ACE chemotherapy resulting in a complete remission. Elevated calcitonin levels, detected at diagnosis, fell to normal with treatment. He remained without evidence of disease until relapse at 11 months and, with second line cytotoxic agents and subsequent palliative radiotherapy, survived a further 11 months. (orig./MG)

  2. Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging

    OpenAIRE

    Van der Schueren, B J; Hoon, J.N.; Vanmolkot, F H; van Hecken, A; Depre, M; Kane, S.A.; De Lepeleire, I; Sinclair, S R

    2007-01-01

    What is already known about this subjectCapsaicin rapidly produces local neurogenic inflammation (characterized by oedema and erythema) when locally administered to the human skin by binding to the TRPV1 receptor present on dermal sensory nerve endings.In nonhuman primates, a pharmacodynamic assay has been described and validated using capsaicin-induced dermal vasodilation measured by laser Doppler perfusion imaging to assess calcitonin gene-related peptide antagonist activity.Laser Doppler p...

  3. CGRP blockers in migraine therapy

    DEFF Research Database (Denmark)

    Edvinsson, L

    2008-01-01

    Calcitonin gene-related peptide (CGRP) is expressed throughout the CNS and peripheral nervous system, consistent with control of vasodilatation, nociception, motor function, secretion and olfaction. AlphaCGRP is prominently localized in primary afferent C and Adelta fibres of spinal and trigemina...... the effect of released CGRP and to abort acute migraine attacks. The novel approach of reducing available CGRP is limited by the blood-brain barrier; its usefulness may be more as prophylaxis rather than as acute treatment of migraine....

  4. Neuropeptides and the Microbiota-Gut-Brain Axis

    OpenAIRE

    Holzer, Peter; Farzi, Aitak

    2014-01-01

    Neuropeptides are important mediators both within the nervous system and between neurons and other cell types. Neuropeptides such as substance P, calcitonin gene-related peptide and neuropeptide Y (NPY), vasoactive intestinal polypeptide, somatostatin and corticotropin-releasing factor are also likely to play a role in the bidirectional gut-brain communication. In this capacity they may influence the activity of the gastrointestinal microbiota and its interaction with the gut-brain axis. Curr...

  5. Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma.

    OpenAIRE

    Blomqvist, C; Risteli, L; Risteli, J.; Virkkunen, P.; Sarna, S.; Elomaa, I.

    1996-01-01

    Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptid...

  6. Développement de formulations sèches de protéines pour inhalation

    OpenAIRE

    Depreter, Flore

    2012-01-01

    A number of therapeutic proteins are used for long in clinical practice. These include for example insulin, calcitonine, growth hormone, and parathyroid hormone for the treatment of various systemic disorders, as well as protein antigens in vaccine formulations. Due to the recent developments in biochemical engineering and in the comprehension of the physiopathology of many diseases, peptides and proteins are expected to become a drug class of increasing importance. Recently, novel biological...

  7. Mixed Medullary-follicular Thyroid Carcinoma: Report of a Case and Review of the Literature

    Institute of Scientific and Technical Information of China (English)

    Xiangtao Ma; Liwei Yu; Jing Fu; Shan Wang; Ruyu Du; Zhirong Cui

    2005-01-01

    @@ Mixed medullary-follicular carcinomas (MMFCs) are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. These tumors are rare and less than 40 cases have been described in the literature since the early 1980s.[1] The term medullary-follicular thyroid carcinoma denotes a tumor which exhibits the features of a medullary carcinoma and shows positive expression of calcitonin on immunohistochemistry.

  8. The contribution of the genomes of a termite and a locust to our understanding of insect neuropeptides and neurohormones

    Directory of Open Access Journals (Sweden)

    Jan Adrianus Veenstra

    2014-11-01

    Full Text Available The genomes of the migratory locust Locusta migratoria and the termite Zootermopsis nevadensis were mined for genes encoding neuropeptides, neurohormones and their G-protein coupled receptors (GPCRs. Both species have retained a larger number of neuropeptide and neuropeptide GPCRs than the better known holometabolous insect species, while other genes that in holometabolous species appear to have a single transcript produce two different precursors in the locust, the termite or both. Thus the recently discovered CNMa neuropeptide gene has two transcripts predicted to produce two structurally different CNMa peptides in the termite, while the locust produces two different myosuppressin peptides in the same fashion. Both these species also have a calcitonin gene, which is different from the gene encoding the calcitonin-like insect diuretic hormone. This gene produces two types of calcitonins, calcitonins A and B. It is also present in Lepidoptera and Coleoptera and some Diptera, but absent from mosquitoes and Drosophila. However, in holometabolous insect species, only the B transcript is produced. Their putative receptors were also identified. In contrast, Locusta has a highly unusual gene that codes for a salivation stimulatory peptide. The Locusta genes for neuroparsin and vasopressin are particularly interesting. The neuroparsin gene produces five different transcripts, of which only one codes for the neurohormone identified from the corpora cardiaca. The other four transcripts code for neuroparsin-like proteins, which lack four amino acid residues, and that for that reason we called neoneuroparsins. The number of transcripts for the neoneuroparsins is about two hundred times larger than the number of neuroparsin transcripts. The first exon and the putative promoter of the vasopressin genes, of which there are about seven copies in the genome, is very well conserved, but the remainder of these genes is not. The relevance of these findings is

  9. Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus

    DEFF Research Database (Denmark)

    Lindberger, M; Schröder, H D; Schultzberg, M;

    1989-01-01

    Standardised skin biopsies followed by immunohistochemical examination for the presence of terminal nerve fibres reacting for neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) were evaluated. Healthy subjects regularly displayed free nerve endings of both fibre types...... in the dermis layers. Five type I diabetes patients without clinical or neurophysiological evidence of polyneuropathy also had reduced density of both fibre types, being significant for CGRP fibres when compared with controls. Skin biopsy with immunohistochemical staining for neuropeptides may represent...

  10. pH-responsive and enzymatically-responsive hydrogel microparticles for the oral delivery of therapeutic proteins: Effects of protein size, crosslinking density, and hydrogel degradation on protein delivery.

    Science.gov (United States)

    Koetting, Michael Clinton; Guido, Joseph Frank; Gupta, Malvika; Zhang, Annie; Peppas, Nicholas A

    2016-01-10

    Two potential platform technologies for the oral delivery of protein therapeutics were synthesized and tested. pH-responsive poly(itaconic acid-co-N-vinyl-2-pyrrolidone) (P(IA-co-NVP)) hydrogel microparticles were tested in vitro with model proteins salmon calcitonin, urokinase, and rituximab to determine the effects of particle size, protein size, and crosslinking density on oral delivery capability. Particle size showed no significant effect on overall delivery potential but did improve percent release of encapsulated protein over the micro-scale particle size range studied. Protein size was shown to have a significant impact on the delivery capability of the P(IA-co-NVP) hydrogel. We show that when using P(IA-co-NVP) hydrogel microparticles with 3 mol% tetra(ethylene glycol) dimethacrylate crosslinker, a small polypeptide (salmon calcitonin) loads and releases up to 45 μg/mg hydrogel while the mid-sized protein urokinase and large monoclonal antibody rituximab load and release only 19 and 24 μg/mg hydrogel, respectively. We further demonstrate that crosslinking density offers a simple method for tuning hydrogel properties to variously sized proteins. Using 5 mol% TEGDMA crosslinker offers optimal performance for the small peptide, salmon calcitonin, whereas lower crosslinking density of 1 mol% offers optimal performance for the much larger protein rituximab. Finally, an enzymatically-degradable hydrogels of P(MAA-co-NVP) crosslinked with the peptide sequence MMRRRKK were synthesized and tested in simulated gastric and intestinal conditions. These hydrogels offer ideal loading and release behavior, showing no degradative release of encapsulated salmon calcitonin in gastric conditions while yielding rapid and complete release of encapsulated protein within 1h in intestinal conditions.

  11. Sensory nerves in man and their role in primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2001-01-01

    The sensory innervation of intracranial vessels originate in the trigeminal ganglion and comprise the following signal substances; calcitonin gene-related peptide (CGRP), substance P, neurokinin A, pituitary adenylate cyclase activating peptide (PACAP) and nitric oxide (NO). Studies in patients h...... with triptan administration, acting via 5-HT(1B/1D) receptors, head pain subside and neuropeptide release normalise. These data show the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches....

  12. Carbocalcitonin treatment in Sudeck's atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Nuti, R.; Vattimo, A.; Martini, G.; Turchetti, V.; Righi, G.A.

    1987-02-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

  13. Basic fibroblast growth factor attenuates the degeneration of injured spinal cord motor endplates**

    Institute of Scientific and Technical Information of China (English)

    Jianlong Wang; Jianfeng Sun; Yongxiang Tang; Gangwen Guo; Xiaozhe Zhou; Yanliang Chen; Minren Shen

    2013-01-01

    The distal end of the spinal cord and neuromuscular junction may develop secondary degeneration and damage fol owing spinal cord injury because of the loss of neural connections. In this study, a rat model of spinal cord injury, established using a modified Al en’s method, was injected with basic fibroblast growth factor solution via subarachnoid catheter. After injection, rats with spinal cord injury displayed higher scores on the Basso, Beattie and Bresnahan locomotor scale. Motor function was also wel recovered and hematoxylin-eosin staining showed that spinal glial scar hyperplasia was not apparent. Additional y, anterior tibial muscle fibers slowly, but progressively, atrophied. Immunohistochemical staining showed that the absorbance values of calcitonin gene related pep-tide and acetylcholinesterase in anterior tibial muscle and spinal cord were similar, and injection of basic fibroblast growth factor increased this absorbance. Results showed that after spinal cord injury, the distal motor neurons and motor endplate degenerated. Changes in calcitonin gene related pep-tide and acetylcholinesterase in the spinal cord anterior horn motor neurons and motor endplate then occurred that were consistent with this regeneration. Our findings indicate that basic fibroblast growth factor can protect the endplate through attenuating the decreased expression of calcitonin gene related peptide and acetylcholinesterase in anterior horn motor neurons of the injured spinal cord.

  14. Chitosan-aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation.

    Science.gov (United States)

    Werle, Martin; Takeuchi, Hirofumi

    2009-03-31

    In order to improve the systemic uptake of therapeutic peptides/proteins after oral administration, the polymer-protease inhibitor conjugate chitosan-aprotinin was synthesised and polyelectrolyte complexes between negatively charged multilamellar vesicles (MLV) and positively charged chitosan-aprotinin conjugate were prepared. It could be demonstrated that chitosan-aprotinin was capable of significantly inhibiting Trypsin in vitro in concentrations of 0.05% and 0.1%, whereas no inhibition was observed in the presence of 0.1% chitosan. The size range of the prepared MLV was between 3 and 4.5microm and the initially negative zeta potential (ca. -90mV) of the core liposomes switched to a positive value after polymer coating (ca. +40mV). Confocal laser microscopy studies showed comparable mucoadhesive properties of chitosan-aprotinin coated MLV and chitosan coated MLV. In comparison to calcitonin in solution, the area above the blood calcium concentration-time curve (AAC) after oral administration of calcitonin loaded chitosan coated MLV to rats increased around 11-fold, and around 15-fold in the case of calcitonin loaded chitosan-aprotinin coated MLV. Data gained in the current study are believed to contribute to the development of novel polymer-protease inhibitor based delivery systems.

  15. cAMP-synthesis in a medullary thyroid carcinoma cell line: response to adrenergic agents and prostaglandines.

    Science.gov (United States)

    Mertens, P R; Goretzki, P E; Keck, E

    1999-01-01

    Calcitonin secretion by C-cells is mediated through intracellular 3'5'-cyclic adenosine monophosphate (cAMP) and calcium signaling. Calcitonin release stimulation tests may take advantage of both signaling cascades in screening for medullary thyroid carcinomas (MTC). To elucidate the regulation of the adenylyl cyclase system we have determined cAMP levels of a calcitonin-expressing MTC cell line (RG) after exposure to adrenergic agents and prostaglandines. In early passages (20-30) cAMP concentrations were significantly elevated in RG cells after exposure to beta-adrenergic agents and prostaglandines E1 and E2. In advanced passages (60-80) the beta-adrenergic response was no longer detectable and adrenergic receptors were uncoupled from the adenylyl cyclase complex; while the effect of prostaglandines E1 and E2 remained unaffected. Preincubation with dexamethasone, in a process requiring protein new synthesis, re-established the adrenergic response in later passages, indicating that RG cells dedifferentiated in culture over time. Our in vitro findings suggest that MTC cell dedifferentiation may be accompanied by adrenergic receptor-uncoupling from the adenylate cyclase system and that this process may be reversed by dexamethasone incubation.

  16. Correlation Analysis of Exercise-Induced Changes in Plasma Trace Element and Hormone Levels During Incremental Exercise in Well-Trained Athletes.

    Science.gov (United States)

    Soria, Marisol; Anson, Miguel; Escanero, Jesús F

    2016-03-01

    This study analyzes the relationship between hormonal changes induced by exercise and variations in trace elements associated with oxidative stress during incremental exercise. Nineteen well-trained endurance athletes performed a cycle ergometer test: after a warm-up of 10 min at 2.0 W kg(-1), workload increased by 0.5 W kg(-1) every 10 min until exhaustion. The analysis was controlled for prior diet and activity patterns, levels of exercise training, and time of day (circadian rhythms). Whole blood lactate concentration and plasma concentrations of ions (Zn, Se, Mn, and Co), insulin, glucagon, aldosterone, thyroid stimulating hormone (TSH), calcitonin, and parathyroid hormone (PTH) were measured at rest; at the end of each stage; and 3, 5, and 7 min post-exercise. The statistical analysis involved paired non-parametric tests and correlation coefficients. No significant differences were found in Mn or Co levels as a function of exercise intensity. Zn and Se levels at the end of the exercise protocol and over the recovery time were significantly different to baseline. Further, Zn levels were significantly correlated with aldosterone, calcitonin, and PTH levels, while Se levels were associated with aldosterone, calcitonin, and TSH levels. Our results indicate several different patterns of association between acute changes in hormone concentrations and variations in trace element concentrations related to oxidative stress during submaximal exercise.

  17. Effects of intermedin1-53 on myocardial fibrosis

    Institute of Scientific and Technical Information of China (English)

    Xiaoling Yang; Huiping Zhang; Yuexia Jia; Lan Ni; Guizhong Li; Lihua Xue; Yideng Jiang

    2013-01-01

    Intermedin (IMD) is a member of the calcitonin/calcitonin gene-related peptide (CGRP) family and has similar or more potent cardiovascular actions than adrenomedullin (ADM) and any other CGRP.The aim of the present work is to study the effects of IMD1-53 on cardiac fibroblast fibrosis in vivo and in vitro.Myocardial infarction model was prepared by ligating rats' left anterior descending coronary artery.Mesenchymal collagen contents in the left ventricle were accessed by Sirius-red stain.Heart functions were explored by hemodynamic changes,Expression of Ⅰ and Ⅲ type collagens,IMD1-53,receptor activity-modifying proteins (RAMP)1/2/3,and calcitonin receptor-like receptor (CRLR) in left ventricle were detected by western blot analysis.Cardiac flbroblasts (CFbs) fibrosis was induced by treating the cells with aldosterone (ALD).CFbs proliferation and the hydroxyprollne contents in supernatants were determined by 3-[4,5-dimehyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide assay and enzyme-linked immunosorbent assay.Heart function was decreased in myocardial infarction model rats.Expression of type I and type Ⅲ collagens in infarcted zone in myocardial rats was higher than those in the sham-operated group.IMD1-53,RAMP,and CRLR in left ventricle were also up-regulated.In vitro experiment showed that ALD was a powerful stimulator of CFbs activation.IMD1-53 decreased ALD-induced CFbs proliferation in a dose-dependent manner.Moreover,CGRP8-37and ADM22-52 remarkably blocked the effect of IMD1-53 on ALD-induced myocardial cell fibrosis.IMD could be involved in the onset of cardiac fibrosis.Like ADM,IMD1-53 exerts an antifibrotic effect on CFbs,which might be mediated by CRLR/RAMP complex and ADM receptor.

  18. The 14th quality control survey for radioisotope in vitro tests in Japan, 1992

    Energy Technology Data Exchange (ETDEWEB)

    1993-11-01

    This report presents the results of the 14th quality control nationwide survey. Of 490 facilities performing RI in vitro tests as of December 1992, 261 (53.3%) participated in the present 1992 survey. Free testosterone and renin were added to the following conventional 37 test items: adrenocorticotropic hormone (ACTH), growth hormone (GH), somatomedin C, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, thyroid stimulating hormone (TSH), triiodothyronine (T[sub 3]), free T[sub 3], thyroxine (T[sub 4]), free T[sub 4], T[sub 3] uptake, thyroglobulin, T[sub 3] binding globulin (TBG), parathyroid hormone (PTH), calcitonin, insulin, C-peptide, glucagon, gastrin, testosterone, estradiol, progesterone, 17[alpha]-hydroxyprogesterone, aldosterone, cortisol, immunoglobulin E (IgE), digoxin, [alpha]-fetoprotein, carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), CA125, CA19-9, CA15-3, prostatic acid phosphatase (PAP), [beta][sub 2]-microglobulin, and ferritin. Measurement data for each kit were analyzed by a mean value of measurements, standard deviation, and coefficient of variation (CV). Both 'within kit variation' between facilities and 'between kit variation' showed a CV of 20% or less for GH, somatomedin C, TSH, T[sub 3], T[sub 4], T[sub 3] uptake, TBG, cortisol, IgE, CA125, PAP, and [beta][sub 2]-microglobulin, revealing satisfactory results. There was a great 'within kit variation' between facilities in ACTH, free T[sub 4], and calcitonin; and there was a great 'between kit variation' in ACTH, LH, free T[sub 4], thyroglobulin, PTH, calcitonin, and [alpha]-fetoprotein. (N.K.).

  19. 18F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    To evaluate the performance of 18F-l-dihydroxyphenylalanine (18F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone 18F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. 18F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of 18F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. 18F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by 18F-DOPA PET/CT. (orig.)

  20. Endothelial Restoration of Receptor Activity-Modifying Protein 2 Is Sufficient to Rescue Lethality, but Survivors Develop Dilated Cardiomyopathy.

    Science.gov (United States)

    Kechele, Daniel O; Dunworth, William P; Trincot, Claire E; Wetzel-Strong, Sarah E; Li, Manyu; Ma, Hong; Liu, Jiandong; Caron, Kathleen M

    2016-09-01

    RAMPs (receptor activity-modifying proteins) serve as oligomeric modulators for numerous G-protein-coupled receptors, yet elucidating the physiological relevance of these interactions remains complex. Ramp2 null mice are embryonic lethal, with cardiovascular developmental defects similar to those observed in mice null for canonical adrenomedullin/calcitonin receptor-like receptor signaling. We aimed to genetically rescue the Ramp2(-/-) lethality in order to further delineate the spatiotemporal requirements for RAMP2 function during development and thereby enable the elucidation of an expanded repertoire of RAMP2 functions with family B G-protein-coupled receptors in adult homeostasis. Endothelial-specific expression of Ramp2 under the VE-cadherin promoter resulted in the partial rescue of Ramp2(-/-) mice, demonstrating that endothelial expression of Ramp2 is necessary and sufficient for survival. The surviving Ramp2(-/-) Tg animals lived to adulthood and developed spontaneous hypotension and dilated cardiomyopathy, which was not observed in adult mice lacking calcitonin receptor-like receptor. Yet, the hearts of Ramp2(-/-) Tg animals displayed dysregulation of family B G-protein-coupled receptors, including parathyroid hormone and glucagon receptors, as well as their downstream signaling pathways. These data suggest a functional requirement for RAMP2 in the modulation of additional G-protein-coupled receptor pathways in vivo, which is critical for sustained cardiovascular homeostasis. The cardiovascular importance of RAMP2 extends beyond the endothelium and canonical adrenomedullin/calcitonin receptor-like receptor signaling, in which future studies could elucidate novel and pharmacologically tractable pathways for treating cardiovascular diseases. PMID:27402918

  1. {sup 18}F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Archier, Aurelien; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Heimburger, Celine [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Morange, Isabelle [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Schneegans, Olivier [Paul Strauss Cancer Center, Department of Nuclear Medicine, Strasbourg (France); Abdullah, Ahmad Esmaeel [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Imperiale, Alessio [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); ICube, UMR 7357 University of Strasbourg/CNRS and FMTS, Faculty of Medicine, Strasbourg (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France)

    2016-06-15

    To evaluate the performance of {sup 18}F-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone {sup 18}F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. {sup 18}F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of {sup 18}F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. {sup 18}F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by {sup 18}F-DOPA PET/CT. (orig.)

  2. 125I-labeling and purification of peptide hormones and bovine serum albumin

    International Nuclear Information System (INIS)

    The iodination and separation of various diagnostically and/or experimentally important peptides including (Tyr1)-somatostatin-14, rat Tyr-α-calcitonin gene-related peptide (23-37), motilin and vasoactive intestinal peptide, furthermore bovine serum albumin are described. All species were iodinated by the iodogen method. The 125I-labeled peptide products were separated by reversed-phase HPLC, the specific activities of mono-iodinated forms are near identical with the theoretical value. The labeled bovine serum albumin was separated by Sephadex G-100 gel filtration. (author)

  3. Is Gastrectomy-Induced High Turnover of Bone with Hyperosteoidosis and Increase of Mineralization a Typical Osteomalacia?

    OpenAIRE

    Takashi Ueyama; Yuta Yamamoto; Kazuki Ueda; Aiji Yajima; Yoshimasa Maeda; Yasunobu Yamashita; Takao Ito; Yoshihiro Tsuruo; Masao Ichinose

    2013-01-01

    Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or change...

  4. A Case of Primary Hyperparathyroidism Found by Parathyroid Crisis

    OpenAIRE

    Sakuragi, Shizu; Taguchi, Akihiko; Miyazaki, Mutsuko; Mitani, Noriyuki; MATSUDA, Kazuyuki; Fukuda, Naofumi; Inoue, Yasushi

    2004-01-01

    A 75-year-old women, who had been well until 2 weeks ago, consulted a phychiatrist because of stupor and appetite loss. A high serum calcium level (16.4mg/dl) was found and she was referred to our department. Calcium level rapidly increased to 25.2 mg/dl within a week regardless of a large amount of saline infusion with simultaneous administation of diuretics, calcitonin and prednisolone. Serum calsium level decreased gradually after six times of hemodialyses and infusion of bisphosphonate, p...

  5. Value of various radiological techniques for follow-up of Camurati-Engelmann disease

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, K.R.; Fritz, P.; Bihl, H.; Lenarz, T.; Weise, D.; Baldauf, G.

    1987-09-01

    Camurati-Engelmann disease is a rare progressive bone dysplasia; involvement of the skull base can lead to deafness, vestibular disturbances, facial paralysis and damage to the optic nerves. Treatment with corticosteroids, calcitonin and diphosphonates promises only very limited success. Conservative treatment of compression of the cranial nerves is almost ineffective, but the aim of surgical treatment is decompression of involved nerves. The differential diagnosis depends on radiological findings and clinical symptoms. Follow-up depends on radiographic examination and skeletal scintigraphy for showing the extent of the disease. CT may help in demonstrating compression of cranial nerves and define the indications for surgical decompression.

  6. A Case of Medullary Thyroid Carcinoma with de novo V804M RET Germline Mutation

    OpenAIRE

    Choi, Young Sik; Kwon, Hye Jung; Kim, Bu Kyung; Kwon, Su Kyoung; Park, Yo Han; Kim, Jeong Hoon; Jung, Sang Bong; Lee, Chang Hoon; Lee, Seong Keun; UCHINO, SHINYA

    2013-01-01

    Many cases of RET proto-oncogene mutations of hereditary medullary thyroid carcinoma (MTC) have been reported in Korea. However, MTC with V804M RET proto-oncogene germline mutations have not been reported in Korea. A 33-yr-old man was diagnosed with a 0.7-cm sized thyroid nodule. Laboratory testing revealed serum calcitonin was elevated. The patient underwent total thyroidectomy with central compartment neck dissection for the thyroid tumor. RET gene analysis was performed in both the index p...

  7. Minimizing acylation of peptides in PLGA microspheres

    OpenAIRE

    Zhang, Ying; Schwendeman, Steven P.

    2012-01-01

    The main objective of this study was to characterize and find mechanisms to prevent acylation of therapeutic peptides encapsulated in glucose-star poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. The effect of addition of divalent cation salts CaCl2, MnCl2 as well as carboxymethyl chitosan (CMCS) on inhibition of acylation of octreotide (Oct), salmon calcitonin (sCT), and human parathyroid hormone (hPTH) was evaluated. Peptide content and integrity inside the degrading microspheres was ...

  8. The role of PET in thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Seok, Yeo Jeong [College of Medicine, Ulsan Univ., Seoul (Korea, Republic of)

    2002-06-01

    The role of PET in the diagnosis and management of thyroid cancer is discussed. The major role of F-18 FDG PET is in patients with discordant negative I-131 scan and a positive serum thyroglobulin values. F-18 FDG PET scan localized metastatic sites in I-131 scan-negative thyroid carcinoma patients with high accuracy. F-18 PET is also valuable in medullary thyroid cancer with high calcitonin level. Focal thyroid uptake in patients with non-thyroidal disease has high likelihood of thyroid cancer.

  9. Innervation of the human middle meningeal artery

    DEFF Research Database (Denmark)

    Edvinsson, L; Gulbenkian, S; Barroso, C P;

    1998-01-01

    The majority of nerve fibers in the middle meningeal artery and branching arterioles are sympathetic, storing norepinephrine and neuropeptide Y (NPY). A sparse supply of fibers contain acetylcholinesterase activity and immunoreactivity toward vasoactive intestinal peptide (VIP), peptidine histidine...... methionine (PHM), and calcitonin gene-related peptide (CGRP). Only few substance P and neuropeptide K immunoreactive fibers are noted. Electronmicroscopy shows axons and terminals at the adventitial medial border of the human middle meningeal artery, with a fairly large distance to the smooth muscle cells...

  10. Bone and mineral metabolism in hyperthyroidism

    International Nuclear Information System (INIS)

    A 47Ca calcitonin study is described which is used in combination with a conventional balance study in 5 patients with hyperthyroidism both before and after therapy and in 1 control subject. The experimentally obtained data were analyzed according to Wendeberg and Dymling. The magnitude of the 47Ca loss through perspiration could not be determined. This fact can affect the rate of accretion but not the other parameters of calcium kinetics. A markedly flow of tracer into bone (inflow, internal disappearance, accretion, rate of accretion) and of calcium out of bone (resorption, outflow) was observed

  11. MANAGEMENT OF ACUTE RENAL FAILURE WITH DELAYED HYPERCALCEMIA SECONDARY TO SARCOCYSTIS NEURONA-INDUCED MYOSITIS AND RHABDOMYOLYSIS IN A CALIFORNIA SEA LION (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Alexander, Amy B; Hanley, Christopher S; Duncan, Mary C; Ulmer, Kyle; Padilla, Luis R

    2015-09-01

    A 3-yr-old captive-born California sea lion (Zalophus californianus) developed Sarcocystis neurona-induced myositis and rhabdomyolysis that led to acute renal failure. The sea lion was successfully managed with fluid therapy, antiprotozoals, antibiotics, anti-inflammatories, antiemetics, gastroprotectants, and diuretics, but developed severe delayed hypercalcemia, a syndrome identified in humans after traumatic or exertion-induced rhabdomyolysis. Treatment with calcitonin was added to the management, and the individual recovered fully. The case emphasizes that animals with rhabdomyolysis-induced renal failure risk developing delayed hypercalcemia, which may be life threatening, and calcium levels should be closely monitored past the resolution of renal failure.

  12. [Progression of the mechanism study on experimental migraine treated with acupuncture in rat model].

    Science.gov (United States)

    Liu, Lu; Pei, Pei; Wang, Linpeng

    2016-03-01

    In the paper, by taking acupuncture and migraine as the key words to retrieve CNKI and PubMed database, the literature analysis was done on the mechanism study on experimental migraine treated with acupuncture in rat model. The results showed that acupuncture mechanism study focused on the regulation and control of the relevant neurotransmitters/neuromodulators of migraine, such as calcitonin gene-related peptide (CGRP), serotonin (5-HT), nitric oxide (NO), etc. Moreover, in the paper, the review had been done on the neurotransmitters/neuromodulators involved in the study.

  13. The Role of Cdk5 in Neuroendocrine Thyroid Cancer

    OpenAIRE

    Pozo, Karine; Castro-Rivera, Emely; Tan, Chunfeng; Plattner, Florian; SCHWACH, GERT; Siegl, Veronika; Meyer, Douglas; Guo, Ailan; Gundara, Justin; Mettlach, Gabriel; RICHER, Edmond; Guevara, Jonathan A.; Ning, Li; Tsai, Li-Huei; Sun, Xiankai

    2013-01-01

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from calcitonin-secreting parafollicular cells, or C cells. We found that Cdk5 and its cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity promotes MTC proliferation. A conditional MTC mouse model was generated and corroborated the role of aberrant Cdk5 activation in MTC. C cell-specific overexpression of p25 caused rapid C cell hyperplasia leading to lethal MTC, which was arrested by repre...

  14. Mechanisms of calcium transport in small intestine. Progress report, March 1, 1976--September 30, 1977. [Chickens, rats, lead

    Energy Technology Data Exchange (ETDEWEB)

    DeLuca, H.F.

    1977-01-01

    Progress is reported on the following research projects: subcellular location of 1,25-dihydroxyvitamin D/sub 3/(1,25-(OH)/sub 2/D/sub 3/) in intestine of chickens; studies on receptor proteins in intestine for 1,25-(OH)/sub 2/D3; studies on intestinal cytosol receptors in chickens and rats; control of intestinal calcium transport; effect of calcitonin on 25-OH-D/sub 3/-1-hydroxylase; isolation and identification of the active principle of Solonum glaucophyllum, the South American plant that causes metastatic calcification and death to grazing animals; and studies on lead transport in vitro and in vivo. (HLW)

  15. Spectroscopic characterization of bone tissue of experimental animals after glucocorticoid treatment and recovery period

    Science.gov (United States)

    Mitić, Žarko J.; Najman, Stevo J.; Cakić, Milorad D.; Ajduković, Zorica R.; Ignjatović, Nenad L.; Nikolić, Ružica S.; Nikolić, Goran M.; Stojanović, Sanja T.; Vukelić, Marija Đ.; Trajanović, Miroslav D.

    2014-09-01

    The influence of glucocorticoids on the composition and mineral/organic content of the mandible in tested animals after recovery and healing phase was investigated in this work. The results of FTIR analysis demonstrated that bone tissue composition was changed after glucocorticoid treatment. The increase of calcium, magnesium, phosphorus content and mineral part of bones was statistically significant in recovery phase and in treatment phase that included calcitonin and thymus extract. Some changes also happened in the organic part of the matrix, as indicated by intensity changes for already present IR bands and the appearance of new IR bands in the region 3500-1300 cm-1.

  16. Relationship between disorders of bone metabolism and osteoporosis and osteopetrosis in patients during hemodialysis%血液透析患者骨代谢异常与骨质疏松、骨硬化的相关分析

    Institute of Scientific and Technical Information of China (English)

    辛华玲; 郑宁华; 蒋丽; 姜志明; 姜有贵

    2001-01-01

    @@Background:Disorders of bone metabolism such as osteoporosis,osteomalacia,osteopetrosis,and osteitis fibrosa are main clinical manifestations in patients with ureamia.It was reported that immunodificiency was involved in disordrs of bone metabolism. Subjects:50 patients with ureamia underwent hemodialysis and 50 healthy subjects.There was no significant difference in age,sex between two groups. Design:Serum calcium,serum inorganic phosphorus,BGP,human calcitonin(H-CT),vitamine D,parathyroid hormone(PTH-M),T lymphocytes subtype were evaluated for healthy subjects and patients with ureamia before and after hemodialysis.

  17. Circulating levels of neuropeptides (CGRP, VIP, NPY) in patients with fulminant hepatic failure

    DEFF Research Database (Denmark)

    Strauss, Gitte Irene; Edvinsson, L; Larsen, F S;

    2001-01-01

    The present study investigated the circulating levels and cerebral fluxes of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) and their relation to cerebral blood flow (CBF) during normoventilation and hyperventilation in patients with fulminant...... in FHF than in cirrhosis, 87 (55-218) vs. 29 (21-42) pmol/L, and 11 (6-29) vs. 5 (3-9)pmol/L, respectively. NPY was normal, none of the measures were related to CBF, and there was no detectable net brain fluxes. Hyperventilation did not alter any of the measures. CGRP and VIP in FHF seem to reflect...

  18. Novel strategies in drug discovery of the calcium-sensing receptor based on biased signaling

    DEFF Research Database (Denmark)

    Thomsen, Alex Rojas Bie; Smajilovic, Sanela; Bräuner-Osborne, Hans

    2012-01-01

    A hallmark of chronic kidney disease is hyperphosphatemia due to renal phosphate retention. Prolonged parathyroid gland exposure to hyperphosphatemia leads to secondary hyperparathyroidism characterized by hyperplasia of the glands and excessive secretion of parathyroid hormone (PTH), which cause...... of hypocalcemia by virtue of it not affecting calcitonin secretion. The present review will focus on recent advancements in understanding signaling and biased signaling of the CaSR, and how that may be utilized to discover new and smarter drugs targeting the CaSR....

  19. Impact of dietary aromatic amino acids on osteoclastic activity.

    Science.gov (United States)

    Refaey, Mona El; Zhong, Qing; Ding, Ke-Hong; Shi, Xing-Ming; Xu, Jianrui; Bollag, Wendy B; Hill, William D; Chutkan, Norman; Robbins, Richard; Nadeau, Hugh; Johnson, Maribeth; Hamrick, Mark W; Isales, Carlos M

    2014-08-01

    We had shown that aromatic amino acid (phenylalanine, tyrosine, and tryptophan) supplementation prevented bone loss in an aging C57BL/6 mice model. In vivo results from the markers of bone breakdown suggested an inhibition of osteoclastic activity or differentiation. To assess osteoclastic differentiation, we examined the effects of aromatic amino acids on early /structural markers as vitronectin receptor, calcitonin receptor, and carbonic anhydrase II as well as, late/functional differentiation markers; cathepsin K and matrix metalloproteinase 9 (MMP-9). Our data demonstrate that the aromatic amino acids down-regulated early and late osteoclastic differentiation markers as measured by real time PCR. Our data also suggest a link between the vitronectin receptor and the secreted cathepsin K that both showed consistent effects to the aromatic amino acid treatment. However, the non-attachment related proteins, calcitonin receptor, and carbonic anhydrase II, demonstrated less consistent effects in response to treatment. Our data are consistent with aromatic amino acids down-regulating osteoclastic differentiation by suppressing remodeling gene expression thus contributing initially to the net increase in bone mass seen in vivo.

  20. Metastatic medullary thyroid cancer: a dramatic response to a systemic chemotherapy (temozolomide and capecitabine regimen

    Directory of Open Access Journals (Sweden)

    Lacin S

    2015-05-01

    Full Text Available Sahin Lacin, Ece Esin, Yusuf Karakas, Suayib Yalcin Department of Medical Oncology, Institute of Cancer, Hacettepe University, Ankara, Turkey Abstract: A 40-year-old male patient presented with increasing serum levels of calcitonin and CEA. He underwent potential curative surgery for medullary thyroid carcinoma, 3 years ago and then 7 months later he had metastasectomy and cervical lymph node dissection for recurrent disease. On admission he had multiple metastatic skin nodules on the chest wall and positron emission tomography–computed tomography revealed multiple visceral metastases as well. The patient had not received any systemic treatment up to that time; therefore, we considered systemic treatment with the new tyrosine kinase inhibitors (vandetanib, cabozantinib, etc. However, since these drugs are only available after cytotoxic chemotherapy, we started temozolomide and capecitabine chemotherapy. After two courses of the treatment all skin nodules disappeared and CEA and calcitonin levels normalized, radiological imaging showed a good partial response. Keywords: medullary thyroid cancer, capecitabine, temozolomide, chemotherapy

  1. Medical Management of Osteoporosis for Elective Spine Surgery.

    Science.gov (United States)

    Hassanzadeh, Hamid; Puvanesarajah, Varun; Dalkin, Alan C

    2016-05-01

    Over 50 million Americans have low bone mass. Poor bone quality is known to complicate spinal fusion surgery, which relies on strong bony purchase to be effective. Unfortunately, many spine surgeons do not perform routine workups for either osteoporosis or osteomalacia. Effective screening and risk factor assessment can allow for appropriate medical management of osteoporosis in the perioperative setting, improving outcomes. Medical management can be grouped into several different categories: vitamins and minerals, bisphosphonates, recombinant parathyroid hormone, estrogen replacement or modification, inhibitors of receptor activator of nuclear factor κ-B ligand (RANKL), and calcitonin. Calcium and vitamin D supplements are the least expensive to prescribe, with minimal side effects and promising animal studies, and thus should be provided to most osteoporotic patients. Recombinant parathyroid hormone can also be considered, as clinical studies have demonstrated impressive results in spine fusion patients. Bisphosphonates, estrogen therapy or selective estrogen receptor modulators, and calcitonin should all be avoided in this patient population given unproven benefit and potentially harmful side-effect profiles. Denosumab is potentially an option, but may not be first line given the general lack of supporting data for its use in perioperative management of spine surgery patients. PMID:27100945

  2. [THE MARKERS OF BONE TISSUE METABOLISM. THE REFERENCE VALUES FOR THE KHANTY-MANSI AUTONOMOUS OKRUG-YUGRA].

    Science.gov (United States)

    Kutchin, R V; Nenenko, N D; Tchernitsina, N V; Maksimova, T A

    2016-03-01

    The article defines reference values of particular markers of metabolism of bone tissue common to residents of the Khanty-Mansi Autonomous Okrug-Yugra. The enzyme-linked immunosorbent assay was applied to analyze blood serum of 86 patients (43 males, 43 females) detecting concentration of C-tailed telopeptide of collagen type I, osteocalcin, calcitonin, parathyroid hormone and 1.25(OH)2 vitamin D. The following reference values were derived. The C-tailed telopeptide (ng/ml): 0.111 (0.071-0.162) for females and 0.146 (0.066-0.255) for males. The osteocalcin (ng/ml): 20.6 (12.9-33.0) for females and 27.6 (12.0-61.9) for males. Calcitonin (pg/ml) - 2.55 (1.90-3.76); parathyroid hormone (pg/ml) - 39 (13-88); 1.25(OH)2 vitamin D (pg/ml) - 10.5 (3.9-46.4). It was also noted that decreasing of average indicators of vitamin D level and increasing of level of parathyroid hormone among residents of the Khanty-Mansi Autonomous Okrug-Yugra can cause increasing of intensity of accumulation of minerals in bone tissue as compared with residents of middle latitudes. PMID:27506104

  3. Regulation of CYP27B1 mRNA Expression in Primary Human Osteoblasts.

    Science.gov (United States)

    van der Meijden, K; van Essen, H W; Bloemers, F W; Schulten, E A J M; Lips, P; Bravenboer, N

    2016-08-01

    The enzyme 1α-hydroxylase (gene CYP27B1) catalyzes the synthesis of 1,25(OH)2D in both renal and bone cells. While renal 1α-hydroxylase is tightly regulated by hormones and 1,25(OH)2D itself, the regulation of 1α-hydroxylase in bone cells is poorly understood. The aim of this study was to investigate in a primary human osteoblast culture whether parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcitonin, calcium, phosphate, or MEPE affect mRNA levels of CYP27B1. Our results show that primary human osteoblasts in the presence of high calcium concentrations increase their CYP27B1 mRNA levels by 1.3-fold. CYP27B1 mRNA levels were not affected by PTH1-34, rhFGF23, calcitonin, phosphate, and rhMEPE. Our results suggest that the regulation of bone 1α-hydroxylase is different from renal 1α-hydroxylase. High calcium concentrations in bone may result in an increased local synthesis of 1,25(OH)2D leading to an enhanced matrix mineralization. In this way, the local synthesis of 1,25(OH)2D may contribute to the stimulatory effect of calcium on matrix mineralization. PMID:27016371

  4. Management of advanced medullary thyroid cancer.

    Science.gov (United States)

    Hadoux, Julien; Pacini, Furio; Tuttle, R Michael; Schlumberger, Martin

    2016-01-01

    Medullary thyroid cancer arises from calcitonin-producing C-cells and accounts for 3-5% of all thyroid cancers. The discovery of a locally advanced medullary thyroid cancer that is not amenable to surgery or of distant metastases needs careful work-up, including measurement of serum calcitonin and carcinoembryonic antigen (and their doubling times), in addition to comprehensive imaging to determine the extent of the disease, its aggressiveness, and the need for any treatment. In the past, cytotoxic chemotherapy was used for treatment but produced little benefit. For the past 10 years, tyrosine kinase inhibitors targeting vascular endothelial growth factor receptors and RET (rearranged during transfection) have been used when a systemic therapy is indicated for large tumour burden and documented disease progression. Vandetanib and cabozantinib have shown benefits on progression-free survival compared with placebo in this setting, but their toxic effect profiles need thorough clinical management in specialised centres. This Review describes the management and treatment of patients with advanced medullary thyroid cancer with emphasis on current targeted therapies and perspectives to improve patient care. Most treatment responses are transient, emphasising that mechanisms of resistance need to be better understood and that the efficacy of treatment approaches should be improved with combination therapies or other drugs that might be more potent or target other pathways, including immunotherapy. PMID:26608066

  5. The 13th quality control survey for radioisotopes in vitro tests in Japan, 1991

    Energy Technology Data Exchange (ETDEWEB)

    1992-11-01

    This paper presents the results of the 13th quality control nationwide survey. Of 568 hospitals performing RI in vitro tests as of December 1991, 280 (49.3%) participated in this survey. The following 37 items were examined: ACTH, 17[alpha]-hydroxyprogesterone, [alpha]-fetoprotein, aldosterone, [beta]2-microglobulin, CA 125, CA 15-3, CA 19-9, calcitonin, CEA, cortisol, C-peptide, digoxin, esteradiol, ferritin, free triiodothyronine (T[sub 3]), free thyroxine (T[sub 4]), FSH, gastrin, GH, glucagon, IgE, insulin, LH, PAP, progesterone, prolactin, PTH, somatomedin C, T[sub 3], T[sub 4], T[sub 3] uptake, TBG, testosterone, thyroglobulin, tissue polypeptide antigen, and TSH. Reliability and safety of measurement values were evaluated based on protein components of serum samples, spontaneous reliability test, time-dependent reliability test, repeated freezing-dissolution test, and serial change test after freezing. 'Within kit variation' between facilities was great especially for ACTH, CA 15-3, CA 19-9, free T[sub 4], calcitonin, gastrin, and testosterone, and was favorable for [beta][sub 2]-microglobulin, CA 125, digoxin, cortisol, IgE, T[sub 3], T[sub 4], T[sub 3] uptake, and TBG. It was noted that there was a great difference in measurement values of free T[sub 3] and free-T[sub 4] between RIA kits and non-isotopic kits. (N.K.).

  6. Value of 111In-DTPA-D-Phe-1-octreotide (111In-OCT) and 99mTc-dimercaptosuccinic acid (99mTc-DMSA-V) scans in medullary thyroid carcinoma (MTC)

    International Nuclear Information System (INIS)

    Background: Although serum calcitonin and CEA are sensitive indicators for the presence of MTC, the localization of tumor sites continuous to be a diagnostic challenge, especially, when calcitonin is elevated after curative surgery and conventional radiological techniques fail to disclose the tumor site(s). Methods: In an approach to localize MTC lesions we performed comparative studies in 31 patients with MTC using 99mTc-DMSA(V) and 111In-OCT. Results: 111In-OCT localized the primary tumor in 11 of 17 patients (64 %). In 3 of 6 patients (50 %) with suspected recurrent/metastatic MTC 111In-OCT failed to demonstrate a pathological uptake. 99mTc-DMSA(V) whole body studies detected in 10 of 17 patients (71 %) the primary tumors, whereas in 2 of 3 (66 %) patients with suspected recurrent disease the tumor sites were demonstrable. 99mTc-DMSA(V) scan was able to detect the tumor sites in 3 patients with negative 111In-OCT scans. In 1 of patients the 111In-OCT scan was superior to the 99mTc-DMSA(V) scan. Conclusions: We conclude that 99mTc-DMSA(V) and 111In-OCT studies may be useful for the localization of primary MTC lesions, while both imaging techniques have limited sensitivity in the detection of recurrent disease. A combined use of both scans in patients with MTC is mandatory if all conventional imaging modalities fail to demonstrate the tumor sites. (author)

  7. High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors

    Directory of Open Access Journals (Sweden)

    Messlinger Karl

    2009-04-01

    Full Text Available Abstract Background Morphine and its derivatives are key drugs in pain control. Despite its well-known analgesic properties morphine at high concentrations may be proalgesic. Particularly, short-lasting painful sensations have been reported upon dermal application of morphine. To study a possible involvement of TRP receptors in the pro-nociceptive effects of morphine (0.3 – 10 mM, two models of nociception were employed using C57BL/6 mice and genetically related TRPV1 and TRPA1 knockout animals, which were crossed and generated double knockouts. Hindpaw skin flaps were used to investigate the release of calcitonin gene-related peptide indicative of nociceptive activation. Results Morphine induced release of calcitonin gene-related peptide and sensitized the release evoked by heat or the TRPA1 agonist acrolein. Morphine activated HEK293t cells transfected with TRPV1 or TRPA1. Activation of C57BL/6 mouse dorsal root ganglion neurons in culture was investigated with calcium imaging. Morphine induced a dose-dependent rise in intracellular calcium in neurons from wild-type animals. In neurons from TRPV1 and TRPA1 knockout animals activation by morphine was markedly reduced, in the TRPV1/A1 double knockout animals this morphine effect was abrogated. Naloxone induced an increase in calcium levels similar to morphine. The responses to both morphine and naloxone were sensitized by bradykinin. Conclusion Nociceptor activation and sensitization by morphine is conveyed by TRPV1 and TRPA1.

  8. Intermedin protects against myocardial ischemia-reperfusion injury in hyperlipidemia rats.

    Science.gov (United States)

    Yang, S M; Liu, J; Li, C X

    2014-10-20

    Hyperlipidemia is a well-established risk factor for the development of coronary atherosclerosis, while intermedin (IMD) has been identified as a novel calcitonin/calcitonin gene-related peptide family member involved in cardiovascular protection. However, whether IMD protects against hyperlipidemia-associated myocardial ischemia/reperfusion (MI/R) injury is unknown. We established a hyperlipidemia model using Sprague-Dawley rats, and created a MI/R condition by ligating the cardiac left circumflex artery. The possible pathophysiological role of IMD and its physiological function in MI/R was further studied. The level of IMD significantly decreased in hyperlipidemia rats (P hyperlipidemia rats compared to the sham-operated rats (P hyperlipidemia rats (P hyperlipidemia-associated MI/R injury. Additional IMD could protect cardiac myocytes against MI/R injury via reduction of apoptosis and inflammation in the hyperlipidemia rat model, and thus, it may play a potential role as a novel therapeutic target for cardiac ischemic injury in hyperlipidemic patients.

  9. Evaluation of symptomatic slow-acting drugs in osteoarthritis using the GRADE system

    Directory of Open Access Journals (Sweden)

    Rizzoli René

    2008-12-01

    Full Text Available Abstract Background Symptomatic slow-acting drugs (SYSADOA have been largely studied over the last decade. The objective of this study is to prepare a document providing recommendations for the use of SYSADOA in osteoarthritis (OA. Methods The following interventions were taken into consideration: avocado/soybean unsaponifiables, chondroitin sulfate, diacereine, glucosamine sulfate, hyaluronic acid, oral calcitonin, risedronate, strontium ranelate. Recommendations were based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation system. The GRADE system is based on a sequential assessment of the quality of evidence, followed by assessment of the balance between benefits versus downsides and subsequent judgment about the strength of recommendations. Results Chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid have demonstrated pain reduction and physical function improvement with very low toxicity, with moderate to high quality evidence. Even if pre-clinical data and some preliminary in vivo studies have suggested that oral calcitonin and strontium ranelate could be of potential interest in OA, additional well-designed studies are needed. Conclusion In the benefit/risk ratio, the use of chondroitin sulfate, diacereine, glucosamine sulfate, avocado/soybean unsaponifiables and hyaluronic acid could be of potential interest for the symptomatic management of OA.

  10. Pathophysiological study of diarrhoea in a patient with medullary thyroid carcinoma. Evidence against a secretory mechanism and for the role of shortened colonic transit time.

    Science.gov (United States)

    Rambaud, J C; Jian, R; Flourié, B; Hautefeuille, M; Salmeron, M; Thuillier, F; Ruskoné, A; Florent, C; Chaoui, F; Bernier, J J

    1988-01-01

    Intubation techniques and scintigraphic studies were used to determine the origin and mechanism of diarrhoea in a patient with medullary thyroid carcinoma, high plasma immunoreactive calcitonin and normal circulating serotonin, substance P and prostaglandins E2 and F2 alpha. Normal function of the small intestine was found for the following: (a) absorption tests; (b) water and electrolyte absorption in the proximal jejunum; (c) 24 hour flow rate and composition of fluid entering the colon and (d) gastric emptying rate and small intestinal progression of a normal meal. By contrast, colonic function was markedly impaired in three ways: (a) water absorption was decreased by half; (b) as the main excreted solutes were organic acids, a large electrolyte gap was recorded in faecal water, and (c) colonic transit time of the meal marker was very short, and was in agreement with the rapid transit of ingested radioopaque markers. These data strongly suggest that decreased absorption in the colon secondary to a motor disturbance is the main mechanism of diarrhoea in this case of medullary thyroid carcinoma, while calcitonin induced small intestinal fluid secretion suggested earlier is either non-existent, or only of minor importance. PMID:3371722

  11. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    Science.gov (United States)

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia.

  12. Fluorescently labeled adrenomedullin allows real-time monitoring of adrenomedullin receptor trafficking in living cells.

    Science.gov (United States)

    Schönauer, Ria; Kaiser, Anette; Holze, Cathleen; Babilon, Stefanie; Köbberling, Johannes; Riedl, Bernd; Beck-Sickinger, Annette G

    2015-12-01

    The human adrenomedullin (ADM) is a 52 amino acid peptide hormone belonging to the calcitonin family of peptides, which plays a major role in the development and regulation of cardiovascular and lymphatic systems. For potential use in clinical applications, we aimed to investigate the fate of the peptide ligand after binding and activation of the adrenomedullin receptor (AM1), a heterodimer consisting of the calcitonin receptor-like receptor (CLR), a G protein-coupled receptor, associated with the receptor activity-modifying protein 2 (RAMP2). Full length and N-terminally shortened ADM peptides were synthesized using Fmoc/tBu solid phase peptide synthesis and site-specifically labeled with the fluorophore carboxytetramethylrhodamine (Tam) either by amide bond formation or copper(I)-catalyzed azide alkyne cycloaddition. For the first time, Tam-labeled ligands allowed the observation of co-internalization of the whole ligand-receptor complex in living cells co-transfected with fluorescent fusion proteins of CLR and RAMP2. Application of a fluorescent probe to track lysosomal compartments revealed that ADM together with the CLR/RAMP2-complex is routed to the degradative pathway. Moreover, we found that the N-terminus of ADM is not a crucial component of the peptide sequence in terms of AM1 internalization behavior. PMID:26767744

  13. Cinacalcet attenuates hypercalcemia observed in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors.

    Science.gov (United States)

    Colloton, Matthew; Shatzen, Edward; Wiemann, Bernadette; Starnes, Charlie; Scully, Sheila; Henley, Charles; Martin, David

    2013-07-15

    Excessive secretion of parathyroid hormone-related protein (PTHrP) by tumors stimulates bone resorption and increases renal tubular reabsorption of calcium, resulting in hypercalcemia of malignancy. We investigated the ability of cinacalcet, an allosteric modulator of the calcium-sensing receptor, to attenuate hypercalcemia by assessing its effects on blood ionized calcium, serum PTHrP, and calcium-sensing receptor mRNA in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors. Cinacalcet effectively decreased hypercalcemia in a dose- and enantiomer-dependent manner; furthermore, cinacalcet normalized phosphorus levels, but did not affect serum PTHrP. Ribonuclease protection assay results demonstrated presence of PTHrP receptor, but not calcium-sensing receptor mRNA in C26-DCT tumors. The mechanism by which cinacalcet lowered serum calcium was investigated in parathyroidectomized rats (i.e., without PTH) made hypercalcemic by PTHrP. Cinacalcet attenuated PTHrP-mediated elevations in blood ionized calcium, which were accompanied by increased plasma calcitonin. Taken together these results suggest that the cinacalcet-mediated decrease in serum calcium is not the result of a direct effect on tumor cells, but rather is the result of increased calcitonin release. In summary, cinacalcet effectively reduced tumor-mediated hypercalcemia and corrected hypophosphatemia in mice. Further investigation of cinacalcet for treatment of hypercalcemia of malignancy is warranted.

  14. Absorption-enhancing effects of gemini surfactant on the intestinal absorption of poorly absorbed hydrophilic drugs including peptide and protein drugs in rats.

    Science.gov (United States)

    Alama, Tammam; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-29

    In general, the intestinal absorption of small hydrophilic molecules and macromolecules like peptides, after oral administration is very poor. Absorption enhancers are considered to be one of the most promising agents to enhance the intestinal absorption of drugs. In this research, we focused on a gemini surfactant, a new type of absorption enhancer. The intestinal absorption of drugs, with or without sodium dilauramidoglutamide lysine (SLG-30), a gemini surfactant, was examined by an in situ closed-loop method in rats. The intestinal absorption of 5(6)-carboxyfluorescein (CF) and fluorescein isothiocyanate-dextrans (FDs) was significantly enhanced in the presence of SLG-30, such effect being reversible. Furthermore, the calcium levels in the plasma significantly decreased when calcitonin was co-administered with SLG-30, suggestive of the increased intestinal absorption of calcitonin. In addition, no significant increase in the of lactate dehydrogenase (LDH) activity or in protein release from the intestinal epithelium was observed in the presence of SLG-30, suggestive of the safety of this compound. These findings indicate that SLG-30 is an effective absorption-enhancer for improving the intestinal absorption of poorly absorbed drugs, without causing serious damage to the intestinal epithelium. PMID:26707414

  15. Enhancement of local bone remodeling in osteoporotic rabbits by biomimic multilayered structures on Ti6Al4V implants.

    Science.gov (United States)

    Huang, Ling; Luo, Zhong; Hu, Yan; Shen, Xinkun; Li, Menghuan; Li, Liqi; Zhang, Yuan; Yang, Weihu; Liu, Peng; Cai, Kaiyong

    2016-06-01

    To enhance long-term survival of titanium implants in patients with osteoporosis, chitosan/gelatin multilayers containing bone morphogenetic protein 2(BMP2) and an antiosteoporotic agent of calcitonin (CT) are deposited on the Ti6Al4V (TC4) implants through layer-by-layer (LBL) electrostatic assembly technique. Here, the obtained titanium alloy implant (TC4/LBL/CT/BMP2) can regulate the release of loaded calcitonin and BMP2 agents in a sustaining manner to accelerate the bone formation and simultaneously inhibit bone resorption. In vitro results show that the bone-related cells on TC4/LBL/CT/BMP2 present the lowest production level of tartrate resistant acid phosphatase (TRAP) but the highest (p strength and favorable bone-implant osseointegration. Overall, this study establishes a simple and profound methodology to fabricate a biofunctional TC4 implant for the treatment of local osteoporotic fractures in vivo. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1437-1451, 2016. PMID:26822259

  16. Occurrence of a CGRP-like molecule in siki (Centroscymnus coelolepsis) hydrolysate of industrial origin.

    Science.gov (United States)

    Martínez-Alvarez, Oscar; Guimas, Laurence; Delannoy, Charles; Fouchereau-Peron, Martine

    2007-07-11

    Fish protein hydrolysates (FPH) may have potential as bioactive components in functional foods as nutraceuticals. This study focused on the identification of calcitonin gene-related peptide (CGRP) molecules in FPH. CGRP is a neuropeptide belonging to the calcitonin/CGRP family and is known as potent arterial and venous vasodilator in humans. Hydrolysates of industrial origin were prepared from siki (Centroscymnus coelolepsis) heads and were analyzed for the presence of CGRP-like molecules using specific radioimmunoassays and radioreceptorassays. The biological activity of the CGRP-related molecules was assessed by their ability to stimulate the adenylate cyclase activity in rat liver membranes. They were finally purified using gel exclusion chromatography and high-performance liquid chromatography (HPLC). These molecules presented a molecular weight around 1500-2500 Da and were obtained with a purification factor of 79. The incorporation of FPH with CGRP-like molecules in functional foods could lead to the development of new useful products for health and nutrition markets. PMID:17579425

  17. Bone metabolism in thyroidectomized patients

    International Nuclear Information System (INIS)

    The bone mineral content in the patients who had undergone operation for thyroid carcinoma was measured by quantitative CT. Thirty-eight cases were enrolled as the subjects. All cases were papillary adenocarcinoma of the thyroid. The totally thyroidectomized group consisted of 3 males and 14 females, and the non-totally thyroidectomized group (post-lobectomy) 3 males and 18 females. Thirty-eight healthy males and females were assigned to the control group. For evaluation of bone mineral content, quantitative CT was used and bone mineral content in the patient's lumbar vertebrae was measured. Concurrently, bone metabolic parameter in serum was determined. No significant difference was observed in the mean bone mineral content among the above three groups. To make correction by sex and age, BMC-index was defined as the value that the bone mineral content in each case was divided by the standard mean by the same age and sex. No significant difference was observed in BMC-index among the above three groups. No significant correlation was observed in serum calcitonin level with the bone mineral content and BMC-index. It suggests that no influence is exerted on bone metabolism if serum calcitonin is maintained in the physiological level. (author)

  18. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    Science.gov (United States)

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia. PMID:6150555

  19. Parathyroid adenoma arising within the sternocleidomastoid muscle: a rare complication of autotransplantation.

    Science.gov (United States)

    Touska, Philip; Srikanthan, Ahgi; Amarasinghe, Kavita; Jawad, Susan

    2016-01-01

    A 19-year-old patient presented with slowly enlarging, painless, left-sided cervical mass. She had a background of multiple endocrine neoplasia 2B and had undergone a total thyroidectomy for medullary thyroid carcinoma during childhood. A cervical recurrence was therefore suspected. Ultrasonographic and MRI examination revealed a well-defined lesion within the left sternocleidomastoid muscle. Further evaluation with sestamibi and single-photon emission CT revealed elevated tracer uptake within the lesion. Cytological analysis, following ultrasound-guided sampling, revealed absent staining for calcitonin and blood samples confirmed a normal serum calcitonin level; however, the serum parathyroid hormone level was elevated. Overall, summative findings were consistent with a diagnosis of a parathyroid adenoma arising within the left sternocleidomastoid muscle. Given that this is not a location for a physiological parathyroid tissue, the adenoma might have arisen within the autotransplanted parathyroid tissue, injected into the muscular sheath during thyroidectomy. The clinical, radiological and pathological features are considered in this article. PMID:27440844

  20. Smoking, calcium, calcium antagonists, and aging.

    Science.gov (United States)

    Nicita-Mauro, V

    1990-01-01

    Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action. PMID:2226675

  1. The Anti-Osteoporotic Drug Preferences of Physiatrists: A Multicenter Descriptive Study

    Directory of Open Access Journals (Sweden)

    Yeşim Gökçe Kutsal

    2012-08-01

    Full Text Available Aim: The purpose of this multicenter descriptive study is to determine the preferences of physiatrists in our country for anti-osteoporotic drugs in patients with primary and secondary osteoporosis. Materials and Methods: This study was carried out in 10 provinces of Turkey. The diagnosis of osteoporosis was based on World Health Organization criteria using dual-energy x-ray absorptiometry. Patients with a spine and/or hip T-score ≤-2.5 were considered as osteoporotic. 714 patients over 18 years old with primary or secondary osteoporosis were included in the study. In addition to socio-demographic characteristics and chronic use of medications and/or additional systemic diseases that cause secondary osteoporosis were questioned and antiosteoporotic drugs that are recommended by their physicians were recorded.Results: The physicians’ preferred vitamin D and calcium as the prior treatment both in primary and secondary osteoporosis. The most commonly used anti-osteoporotic agent was alendronate from the biphosphonate group. It was followed by ibandronate, risedronate, strontium ranelate, calcitonin, zoledronate, raloxifene, parathyroid hormone (PTH and hormone replacement therapy (HRT in the primary osteoporosis and risedronate, ibandronate, calcitonin, strontium ranelate, zoledronate, PTH, HRT and raloxifene in the secondary osteoporosis, respectively. Conclusion: The physician should choose the most suitable treatment for the patient based on fracture risk, medical history, previous treatments for osteoporosis, concomitant diseases, treatment-induced risks and benefits, and the relation between financial cost and potential benefit. (Turkish Journal of Osteoporosis 2012;18: 42-6

  2. Tumour markers in germ cell tumours and thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mann, K.

    1988-02-01

    In patients with germ cell tumours of gonadal and extragonadal origin both markers, human chorionic gonadotropin (hCG) and alphafetoprotein (AFP) are madatory for diagnosis and control of treatment. In seminoma, we found preoperatively elevated levels of hCG(+hCG-..beta..) in 42/349 patients (12%) up to 1200 mlU/ml using a polyclonal radioimmunoassay (1. IRP hCG standard 75/537). Lactatedehydrogenase can be useful in marker negative patients. Serum levels reflect tumour burden even if not highly specific. Presently, placental alkaline phosphatase is under discussion for seminoma. However, commercial kits are not available. As a relatively high secretion of hCG/..beta../hCG was found in gestational trophoblastic diseases, this parameters may be useful for differential diagnosis in pregnancy. In the follow-up of patients with differentiated thyroid carcinoma the determination of thyroglobulin (Tg) in combination with ultrasound of the thyroid and X-ray of the chest is sufficient. For Tg-determination thyroid hormone replacement therapy must be discontinued only in rare single cases with borderline levels, which need radioiodtesting additionally. Calcitonin is the most important marker in medullary thyroid carcinoma. Pentagastrin stimulated calcitonin as screening test is necessary, if multiple endocrine adenomatosis or the familial forms are suspected. In single cases benefit came from new scintigraphic methods such as /sup 131/I-metaiodo-benzylguanidine or /sup 201/thallium-chloride.

  3. Osteoporosis in the jawbones: a correlative factor of primary trigeminal neuralgia?

    Science.gov (United States)

    Liu, Li; Wang, Hu; Liu, Na; Yang, Qianmei; Luo, En

    2014-01-01

    Trigeminal neuralgia (TN), a neuropathic disorder of one or both of the trigeminal nerves, occurs most often in people over age 50. Extreme, sporadic, sudden burning or shock-like face pain in common activities greatly lowers quality of life. The precise cause of primary TN remains unknown, but it may be caused by vascular pressing on the trigeminal nerve in its root entry zone (REZ), demyelinization of trigeminal sensory fibers, or jawbone cavity. Accordingly, many treatments carry risks of adverse effects, recurrence, and complications. TN and osteoporosis have similar high-risk populations and a common influential factor - emotional stress - is also closed related to primary TN for calcitonin gene-related peptide and calcitonin. Jawbone cavity, which is a possible pathogenesis of TN, may be another form of jawbone osteoporosis. Therefore, we hypothesized that osteoporosis in jaws could be a correlative factor of primary TN. If this hypothesis is verified, it may suggest specific new ideas for the early preventive treatment of primary TN. PMID:25141822

  4. Aerosol delivered radiolabeled antibodies to ectopic lung carcinoma antigens in scintigraphic tumour detection

    International Nuclear Information System (INIS)

    Biologically specific antibodies offer increased specificity of inhalation scintigraphy in pulmonary malignancy at present limited to detection of airways obstruction. Polypeptide ectopic antigens produced by epithelial lung tumours provide a targeting focus for radiolabeled antibodies. Image resolution using the intravenous route is poor due to the small proportion of the dose targeting to the tumor site and ineffective clearance of the background. The inhalation route minimizes non-specific distribution and utilizes mucociliary clearance as a contrast enhancement mechanism. Mucociliary deposition is cleared more effectively than alveolar deposition. Submicronic aerosol droplets produced by airlet nebulisers ensure peripheral airways penetration and deposition. Affinity purified polyclonal goat antibodies against calcitonin labeled with 150 MBq of Tc-99m are delivered to the lungs to produce dynamic images over 24 hours. Pure synthetic human calcitonin ensures production of monospecific antibodies that can be affinity purified. Labeling with Tc-99m by stannous chloride reduction is effected on the solid phase Sepharose beads. An antibody-antigen concentration gradient over a small distance can be provided with radiolabeled antibodies from aerosol deposition. Histologically neoplastic cells are typically separated from the mucous layer by bronchial mucosa and a thin uninvolved lamina. A localised high concentration of labile antigen is present in extra-cellular spaces at the tumour site. A study is progressing to determine if specific antibody-antigen agglutination contributes towards localised impairment of mucociliary clearance at tumour sites creating contrast

  5. Somatostatin and medullary thyroid carcinoma: potential value in diagnosis and therapy

    International Nuclear Information System (INIS)

    In a prospective study, somatostatin receptor scintigraphy (SRS) was performed in 21 patients with clinical evident tumor tissue or with minimal residual disease. Except liver metastases, all known or proven mass lesions could be delineated by means of SRS, indicating the presence of somatostatin receptors. False-positive results with respect to MTC metastases were obtained by the coincidental occurence of chronic infection sites and receptor expressing tumors other than MTC. In minimal residual disease, a high correlation was found between the results of SRS and determination of calcitonin gradient in selective venous catheterization. Treatment of advanced stages of MTC is a further field of interest. In a therapeutic study no beneficial effect on preexisting diarrhea was observed. A therapeutic effect on tumor growth could not be demonstrated as indicated by a further increase of the calcitonin levels. Further studies are required to evaluate the potential value of somatostatin and its analogs in diagnostic work-up and therapy in patients with MTC. (orig./MG)

  6. Expression of different neuropeptide receptors on osteoblast surface%成骨细胞表面不同神经肽受体的表达

    Institute of Scientific and Technical Information of China (English)

    张学敏; 马文辉; 时述山; 张卫平; 冯志军; 李亚非; 贾恒川; 胡兴茂; 郑晓华

    2011-01-01

    背景:大量研究表明神经因素可调节骨代谢,迄今为止已发现5 种神经肽参与骨代谢过程.目的:观察正常人成骨细胞表面不同神经肽受体的表达.方法:分别以降钙素基因相关肽、酪氨酸羟化酶、P 物质、神经肽Y 的单克隆抗体进行免疫组化染色,观察各种肽类受体在成骨细胞表面的表达情况.另外,利用计算机图像分析系统对染色灰度进行半定量分析.结果与结论:正常人成骨细胞表面有神经肽Y、P物质、酪氨酸羟化酶、降钙素基因相关肽受体表达,这些因子可以通过与相应的受体结合影响细胞生物学特性.不同因子免疫组化染色的灰度值由小到大依次为神经肽Y、降钙素基因相关肽、酪氨酸羟化酶、P物质,神经肽是成骨细胞活性的重要调节因子.%BACKGROUND: A large number of studies have demonstrated that neuropeptide can regulate bone metabolism. There have been five neuropeptides found to participate in the process of bone metabolism.OBJECTIVE: To observe the expression of different neuropeptides on the surface of osteoblasts of healthy adults.METHODS: Calcitonin gene-related peptide, tyrosine hydroxylase, P substance, neuropeptide Y monoclonal antibodies were used for immunohistochemical staining to observe the expression of various neuropeptide receptors on the surface of osteoblasts.In addition, semi-quantitative analysis of staining gray scale was performed through the use of computer image analysis system.RESULTS AND CONCLUSION: Neuropeptide Y, P substance and calcitonin gene-related peptide receptor expression was observed on the surface of osteoblasts of healthy adults and these factors influence cellular biological characteristics after binding with corresponding receptors. The gray value from low to high was in the following sequence, neuropeptide Y, calcitonin gene-related peptide, tyrosine hydroxylase, P substance. Results showed that neuropeptide is an important

  7. Receptors for sensory neuropeptides in human inflammatory diseases: Implications for the effector role of sensory neurons

    International Nuclear Information System (INIS)

    Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues

  8. Host response biomarkers in sepsis: the role of procalcitonin.

    Science.gov (United States)

    Vincent, Jean-Louis; Van Nuffelen, Marc; Lelubre, Christophe

    2015-01-01

    Procalcitonin is the prohormone of calcitonin and present in minute quantities in health. However, during infection, its levels rise considerably and are correlated with the severity of the infection. Several assays have been developed for measurement of procalcitonin levels; in this article, we will briefly present the PCT-sensitive Kryptor(®) test (Brahms, Hennigsdorf, Germany), one of the most widely used assays for procalcitonin in recent studies. Many studies have demonstrated the value of procalcitonin levels for diagnosing sepsis and assessing disease severity. Procalcitonin levels have also been successfully used to guide antibiotic administration. However, procalcitonin is not specific for sepsis, and values need to be interpreted in the context of a full clinical examination and the presence of other signs and symptoms of sepsis.

  9. Q-T interval (QTc) in patients with cirrhosis: relation to vasoactive peptides and heart rate

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Gülberg, V.; Fuglsang, Stefan;

    2007-01-01

    ) and calcitonin gene-related peptide (CGRP) in patients with cirrhosis. In addition, we studied problems with HR correction of QT. MATERIAL AND METHODS: Forty-eight patients with cirrhosis and portal hypertension were studied during a haemodynamic investigation. Circulating levels of ETs and CGRP were determined......OBJECTIVE: Prolonged Q-T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET-1 and ET-3......, but not to the elevated powerful vasoconstrictor (ET-1) or vasodilator (CGRP, ET-3) peptides. The problems with correction of the QT for elevated HR in cirrhosis are complex, and the lowest HR should be applied for determination of the QT....

  10. Q-T interval (QT(C)) in patients with cirrhosis: relation to vasoactive peptides and heart rate

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Gülberg, V; Fuglsang, S;

    2007-01-01

    ) and calcitonin gene-related peptide (CGRP) in patients with cirrhosis. In addition, we studied problems with HR correction of QT. MATERIAL AND METHODS: Forty-eight patients with cirrhosis and portal hypertension were studied during a haemodynamic investigation. Circulating levels of ETs and CGRP were determined......OBJECTIVE: Prolonged Q-T interval (QT) has been reported in patients with cirrhosis who also exhibit profound abnormalities in vasoactive peptides and often present with elevated heart rate (HR). The aim of this study was to relate QT to the circulating level of endothelins (ET-1 and ET-3......, but not to the elevated powerful vasoconstrictor (ET-1) or vasodilator (CGRP, ET-3) peptides. The problems with correction of the QT for elevated HR in cirrhosis are complex, and the lowest HR should be applied for determination of the QT....

  11. [Algodystrophy--Sudeck syndrome].

    Science.gov (United States)

    Moroń, K; Misterka, S; Ciesielska, A; Dorobisz, U

    1993-01-01

    Modern views are presented on the development of algodystrophy illustrated with own material with a detailed description of characteristic cases. In the whole material of 175 patients, four age groups, and two groups according to trauma site (hand and foot) were isolated. All patients were subjected to clinical, X-ray, and some to radioisotope examinations. Greatest number of cases of algodystrophy was found in the age group over 60 years which confirmed the observations of other authors. On the basis of the presented material the authors think that of greatest importance are early diagnosis, treatment with of greatest importance are early diagnosis, treatment with analgesics, blood flow improving drugs, and salmon calcitonin, and rehabilitation treatment. It seems also that treatment with magnetic field may be beneficial--however, too small material of patients makes general conclusions impossible. PMID:7504376

  12. Effects of Compound Rhubarb Pill on Plasma D-lactate and Procalctionin Expressions in Patients with Sepsis%复方大黄片对脓毒症患者血浆 D-乳酸及前降钙素表达的影响

    Institute of Scientific and Technical Information of China (English)

    施伟民

    2014-01-01

    Objective:To study the compound big porn plasma D-lactic acid in patients with sepsis and the former ex-press the effect of calcitonin .Methods:February 2013 to February 2014 ,our hospital surgical of 55 patients with sep-sis ,rhubarb treatment group (30 cases) and non rhubarb treatment group (25 cases) .Rhubarb treatment group given compound rhubarb ,3g/second ,1/8h ,with routine therapy and routine therapy including antibiotics ,shope deep ,Sin-gapore and Thailand can cure;assure the normal supply of water and electrolyte ,and nutrition .The rhubarb treatment group given conventional treatment .Two groups of cases before and after treatment 1d ,4d to determine patients plasma D-lactic acid and calcitonin level changes .Results:The treatment group before treatment the patient’s level of plasma D-lactic acid and calcitonin level before ,with the rhubarb treatment group ,there was no significant difference (P>0.05) , 1d ,4d after treatment plasma D-lactic acid levels rhubarb treatment group was lower than that of rhubarb treatment group (P0.05) .4 days after treatment of two groups of cases before the plasma calcitonin level comparison results of rhubarb treatment group significantly below the rhubarb treatment group as a result ,there is significant difference (P<0.01) . Conclusion:The compound rhubarb could improve intestinal permeability in patients with sepsis ,reduce bacteria trans-location .%目的:研究复方大黄片对脓毒症患者血浆D-乳酸及前降钙素表达的影响。方法:2013年2月-2014年2月入住我院外科的脓毒症患者55例,分为大黄治疗组(30例)和非大黄治疗组(25例)。大黄治疗组给予复方大黄片3g/次,1次/8h服用,附带常规治疗,常规治疗包括抗生素、舒普深、特治星、泰能;保证水和电解质以及营养的正常供给。非大黄治疗组只给予常规治疗。两组病例治疗前和治疗后1d、4d测定血浆D-乳酸和前降钙素水平变化情况。结

  13. Therapeutical uses of 131I

    International Nuclear Information System (INIS)

    Physiology of thyroid gland, pathology of thyroid , papillary, follicular cancer is considered together as differentiated thyroid cancer with very good results under therapy with iodine, invitro determination of calcitonin, search of metastasis, anaplastic carcinoma, as indifferentiated carcinoma with similar results as medullary carcinoma. This work gives a protocol for therapeutical use of 131I , in hyperthyroidism due to Graves-Basedow disease, thyrotoxic adenoma or Plummer disease, toxic multi nodular goiter, subacute thyroiditis. Is studied too the treatment with pharmaceuticals, surgery and radioactive iodine. A recommended use of each and protocol for iodine administration, fixed dose technique, dose estimation,absorbed dose, recommendations about when to use and not use 131I are included in this work

  14. 降钙素原在儿童社区获得性肺炎的临床应用%The role of procalcitonin in children with community acquired pneumonia

    Institute of Scientific and Technical Information of China (English)

    萨日娜; 王爱琼

    2013-01-01

    降钙素原(procalcitonin,PCT)是降钙素的前体物质,是近年来新发现的诊断细菌感染的指标。在儿童社区获得性肺炎中检测其血清浓度,可用于早期估计感染病原体的种类,评价感染的严重程度,指导用药及判断预后等。%Procalcitonin (PCT), a precursor of hormone calcitonin, is used as an indicator of bacterial infections in recent years. PCT plays an important role in early identiifcation of pathogens, evaluation of the severity of infection, medication guidance and prognosis judgment in children with community acquired pneumonia.

  15. The value of the immunohistochemistry in a case of gastric neuroendocrine tumor and thyroid metastasis.

    Science.gov (United States)

    Poiană, Cătălina; Carşote, Mara; Ardeleanu, Carmen; Terzea, Dana; Avramescu, Elena Taina; Neamţu, M C; Miulescu, Rucsandra Dănciulescu

    2011-01-01

    Thyroid metastasis is atypical. We present a 70-year-old female case that was first diagnosed as gastric cancer after surgical approach. Two years later a thyroidectomy was performed and the immunohistochemistry (IHC) profile revealed a neuroendocrine tumor (NET): poorly differentiated neuroendocrine carcinoma (with small cells), with positive reaction for SYN, CROMO, negative for calcitonin, TTF1 and thyreoglobulin. The Ki-67 index was 25%. Considering the unusual metastasis, the IHC exam of the stomach tumor was performed pointing the same features as the thyroid findings. This proved that the thyroid tumor was a metastasis from a primary gastric neoplasia. This is an unusual case of NET because of the thyroid involvement. Nevertheless, the IHC exam played the major role in elucidating the diagnosis and the prognosis of the case. PMID:21424054

  16. Hypercalcemia and altered biochemical bone markers in post-bone marrow transplantation osteopetrosis: a case report and literature review.

    Science.gov (United States)

    Kulpiya, Alisa; Mahachoklertwattana, Pat; Pakakasama, Samart; Hongeng, Suradej; Poomthavorn, Preamrudee

    2012-08-01

    Autosomal recessive osteopetrosis is a rare disorder of bone resorption defect that results in generalized sclerotic bones and bone marrow failure. Allogeneic BMT is the only treatment for cure. One of the complications following a successful BMT is hypercalcemia that is a unique complication in this group of patients. We report a three-yr-old boy with osteopetrosis who developed hypercalcemia following the successful BMT. His maximal calcium level was 13.3 mg/dL. Markedly increased both bone formation and resorption markers were demonstrated along with hypercalcemia. These findings indicated an active donor-derived osteoclastic function and thus bone resorption following the successful donor engraftment in the patient. Treatment with hyperhydration, furosemide and bone resorption inhibitors, calcitonin, and bisphosphonate led to normalization of the serum calcium level. Bone resorption but not bone formation marker was persistently elevated despite having normocalcemia during a 16.5-month follow-up period. PMID:21323826

  17. Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache

    DEFF Research Database (Denmark)

    Kruuse, Christina Rostrup; Frandsen, E; Schifter, S;

    2004-01-01

    Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine...... whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from...... migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce...

  18. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia.

    Science.gov (United States)

    Roman, Carolyn W; Derkach, Victor A; Palmiter, Richard D

    2016-01-01

    The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRP(PBN)) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRP(PBN) neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRP(PBN) neurons to promote anorexia. PMID:27301688

  19. PACAP-38 infusion causes sustained vasodilation of the middle meningeal artery in the rat

    DEFF Research Database (Denmark)

    Bhatt, Deepak K; Gupta, Saurabh; Olesen, Jes;

    2014-01-01

    BACKGROUND: In healthy human volunteers and in migraineurs, pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) infusion caused sustained vasodilation of the middle meningeal artery (MMA) and an immediate as well as a delayed headache. All the study subjects experienced facial flushing....... Mast cells (MCs) might have a role in the long-lasting effect of PACAP-38 infusion. We hypothesized that in mast cell-depleted (MCD) rats the vascular responses to PACAP-38 would be lesser than in control rats because of a lack of vasodilatory products released during MC degranulation. METHODS: MCs...... were depleted by chronic treatment with compound 48/80. The effect of 20 minutes' intravenous (i.v.) infusion of calcitonin gene-related peptide (CGRP), PACAP-38, PACAP(6-38) (PAC-1 receptor antagonist) and PACAP-27 on the diameter of the MMA and on mean arterial blood pressure (MABP) in control...

  20. Emerging migraine treatments and drug targets

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2011-01-01

    Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5......-hydroxytrypamine (5-HT)(1F) receptor agonists, which are in late-stage development. Nitric oxide antagonists are also in development. New forms of administration of sumatriptan might improve efficacy and reduce side effects. Botulinum toxin A has recently been approved for the prophylaxis of chronic migraine....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development. The...

  1. Neurochemical characterization of the vestibular nerves in women with vulvar vestibulitis syndrome.

    Science.gov (United States)

    Bohm-Starke, N; Hilliges, M; Falconer, C; Rylander, E

    1999-01-01

    Women with vulvar vestibulitis syndrome (VVS) have a distinct burning pain provoked by almost any stimuli in the area around the vaginal introitus. In a previous study we observed an increased number of intraepithelial free nerve endings in women with VVS. The aim of the present study was to neurochemically characterize the superficial nerves in the vulvar vestibular mucosa of women with VVS. Immunohistochemical methods were used to detect neuropeptides normally found in various types of nerve fibers. Calcitonin gene-related peptide, which is known to exist in nociceptive afferent nerves, was the only neuropeptide detected in the superficial nerves of the vestibular mucosa. These findings confirm our previous theory that the free nerve endings within the epithelium are nociceptors. PMID:10592432

  2. Significance of measurement of vascular endothelial substances (ET, AT-II and CGRP) in coal mine drillers

    International Nuclear Information System (INIS)

    Objective: To study the effects of hand-arm vibration on the releasing of vascular endothelial substances. Methods: The plasma concentrations of endothelin (ET), angiotensin II (AngII) and calcitonin gene-related peptide (CGRP) were measured by RIA in coal mine drillers with various vibration-exposed duration. Results: With the prolongation of vibration-exposed duration, the plasma concentrations of ET and Ang II increased significantly (p<0.05, p<0.01), whereas the plasma concentrations of CGRP decreased significantly (p<0.05, p<0.01). Conclusion: Long time exposure to hand-arm vibration result in changes of releasing of vascular endothelial substances, which could be related to the vibration-induced vascular impairment and vibration-induced white finger

  3. Migraine in the era of precision medicine.

    Science.gov (United States)

    Zhang, Lv-Ming; Dong, Zhao; Yu, Sheng-Yuan

    2016-03-01

    Migraine is a common neurovascular disorder in the neurologic clinics whose mechanisms have been explored for several years. The aura has been considered to be attributed to cortical spreading depression (CSD) and dysfunction of the trigeminovascular system is the key factor that has been considered in the pathogenesis of migraine pain. Moreover, three genes (CACNA1A, ATP1A2, and SCN1A) have come from studies performed in individuals with familial hemiplegic migraine (FHM), a monogenic form of migraine with aura. Therapies targeting on the neuropeptids and genes may be helpful in the precision medicine of migraineurs. 5-hydroxytryptamine (5-HT) receptor agonists and calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated efficacy in the acute specific treatment of migraine attacks. Therefore, ongoing and future efforts to find new vulnerabilities of migraine, unravel the complexity of drug therapy, and perform biomarker-driven clinical trials are necessary to improve outcomes for patients with migraine. PMID:27127758

  4. Reduced responsiveness of cutaneous microcirculation in essential hypertension--a pilot study

    DEFF Research Database (Denmark)

    Lindstedt, Isak H; Edvinsson, Marie-Louise; Edvinsson, Lars

    2006-01-01

    on their medication. METHOD: The local cutaneous forearm blood flow was measured by Laser-Doppler flowmetry. The blood flow response to local warming (44 degrees C), to the endothelium-dependent vasodilator acetylcholine (ACh), or to the endothelium-independent dilators sodium nitroprusside (SNP) and calcitonin gene......-related peptide (CGRP) administered by iontophoresis were determined. Inflammatory markers and NT-pro brain natriuretic peptide (NT-proBNP) levels in plasma was also measured. Electrocardiograms (ECG) were evaluated and the subjects answered a lifestyle questionnaire. RESULTS: The percentage change in vasodilator...... response to CGRP was significantly lower in the hypertensives compared with normotensives, 285% (95% CI 86-484) vs 764% (95% CI 366-1162) of baseline, p warming was 2191% (95% CI 1574-2807) in normotensives vs 1384% (95% CI 852-1917) in the hypertensives, p

  5. The Role of Cgrp-Receptor Component Protein (Rcp in Cgrp-Mediated Signal Transduction

    Directory of Open Access Journals (Sweden)

    M. A. Prado

    2001-01-01

    Full Text Available The calcitonin gene-related peptide (CGRP-receptor component protein (RCP is a 17-kDa intracellular peripheral membrane protein required for signal transduction at CGRP receptors. To determine the role of RCP in CGRP-mediated signal transduction, RCP was depleted from NIH3T3 cells using antisense strategy. Loss of RCP protein correlated with loss of cAMP production by CGRP in the antisense cells. In contrast, loss of RCP had no effect on CGRP-mediated binding; therefore RCP is not acting as a chaperone for the CGRP receptor. Instead, RCP is a novel signal transduction molecule that couples the CGRP receptor to the cellular signal transduction machinery. RCP thus represents a prototype for a new class of signal transduction proteins that are required for regulation of G protein-coupled receptors.

  6. Lessons learned from the clinical development of oral peptides.

    Science.gov (United States)

    Karsdal, Morten Asser; Riis, Bente Juul; Mehta, Nozer; Stern, William; Arbit, Ehud; Christiansen, Claus; Henriksen, Kim

    2015-05-01

    The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken to date with these oral formulations. Special interest is given to oral salmon calcitonin (CT), glucagon-like peptide-1 (GLP-1), insulin, PYY-(3-36), recombinant human parathyroid hormone (rhPTH(1-31)-NH2) and PTH(1-34), by different technologies. The issues addressed include (i) interaction with water, (ii) interaction with food, (iii) diurnal variation, (iv) inter- and intra-subject variability, (v) correlation between efficacy and exposure and (vi) key deliverables of different technologies. These key lessons may aid research in the development of other oral formulations. PMID:25408230

  7. Neutron diffraction studies of amphipathic helices in phospholipid bilayers

    International Nuclear Information System (INIS)

    The structural feature which is thought to facilitate the interaction of many peptides with phospholipid bilayers is the ability to fold into an amphipathic helix. In most cases the exact location and orientation of this helix with respect to the membrane is not known, and may vary with factors such as pH and phospholipid content of the bilayer. The growing interest in this area is stimulated by indications that similar interactions can contribute to the binding of certain hormones to their cell-surface receptors. We have been using the techniques of neutron diffraction from stacked phospholipid bilayers in an attempt to investigate this phenomenon with a number of membrane-active peptides. Here we report some of our findings with three of these: the bee venom melittin; the hormone calcitonin; and a synthetic peptide representing the ion channel fragment of influenza A M2 protein

  8. Anti-inflammatory actions of acupuncture

    Directory of Open Access Journals (Sweden)

    Freek J. Zijlstra

    2003-01-01

    Full Text Available Acupuncture has a beneficial effect when treating many diseases and painful conditions, and therefore is thought to be useful as a complementary therapy or to replace generally accepted pharmacological intervention. The attributive effect of acupuncture has been investigated in inflammatory diseases, including asthma, rhinitis, inflammatory bowel disease, rheumatoid arthritis, epicondylitis, complex regional pain syndrome type 1 and vasculitis. Large randomised trials demonstrating the immediate and sustained effect of acupuncture are missing. Mechanisms underlying the ascribed immunosuppressive actions of acupuncture are reviewed in this communication. The acupuncture-controlled release of neuropeptides from nerve endings and subsequent vasodilative and anti-inflammatory effects through calcitonine gene-related peptide is hypothesised. The complex interactions with substance P, the analgesic contribution of β-endorphin and the balance between cell-specific pro-inflammatory and anti-inflammatory cytokines tumour necrosis factor-α and interleukin-10 are discussed.

  9. Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders

    DEFF Research Database (Denmark)

    Petersen, K A; Birk, S; Petersen, Kenneth Ahrend;

    2009-01-01

    Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine....... However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 microg kg(-1) min(-1)) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura...... Doppler and the diameter of peripheral arteries by transdermal ultrasound (C-scan). ADM did not induce significantly more headache or migraine compared with placebo (P = 0.58). CBF was unaffected by ADM infusion (global CBF, P = 0.32 and rCBF(MCA), P = 0.38) and the same applied for the V(MCA) (P = 0...

  10. Expression of messenger RNAs for peptides and tyrosine hydroxylase in primary sensory neurons that innervate arterial baroreceptors and chemoreceptors.

    Science.gov (United States)

    Czyzyk-Krzeska, M F; Bayliss, D A; Lawson, E E; Millhorn, D E

    1991-08-01

    Retrograde fiber tracing and in situ hybridization were used to determine expression of mRNAs for preprotachykinin A (ppTA), calcitonin gene related peptide (CGRP), preproenkephalin A (ENK), neuropeptide tyrosine (NPY) and somatostatin (SOM) as well as tyrosine hydroxylase (TH) in the petrosal ganglia primary sensory neurons which innervate carotid sinus baroreceptors and carotid body chemoreceptors. Perfusion of the carotid sinus with the retrogradely transported dye (Fluoro-Gold) labeled primary sensory neurons in petrosal ganglion. Numerous somata in the petrosal ganglion labeled with dye contained mRNAs for all the above peptides, except SOM. Moreover, TH mRNA was found in a substantial number of retrogradely labeled cells in the petrosal ganglion. This study provides information concerning which of the numerous peptides identified in sensory neurons of petrosal ganglion may be involved in modulation of the arterial baroreceptor and chemoreceptor reflexes. PMID:1681484

  11. Arterial hypertension and chronic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S

    2005-01-01

    , calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during......This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic...... the development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial...

  12. Increased arterial compliance in decompensated cirrhosis

    DEFF Research Database (Denmark)

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

    1999-01-01

    of the vasodilator, calcitonin gene-related peptide (CGRP) and mean arterial blood pressure (MAP). METHODS: Arterial compliance (COMPart=deltaV/deltaP) was determined as the stroke volume relative to pulse pressure (i.e. systolic minus diastolic blood pressure) during a haemodynamic evaluation of portal hypertension......BACKGROUND/AIMS: In patients with cirrhosis, the systemic circulation is hyperdynamic with low arterial blood pressure and reduced systemic vascular resistance. The present study was undertaken to estimate the compliance of the arterial tree in relation to severity of cirrhosis, circulating level.......1 x 10(-3) l/mmHg, respectively, p=0.03). The stroke volume did not change significantly with the severity of the disease, but pulse pressure decreased through class A, B, and C (79, 65, and 50 mmHg, respectively, p

  13. Wiping Out CGRP: Potential Cardiovascular Risks.

    Science.gov (United States)

    MaassenVanDenBrink, Antoinette; Meijer, Joris; Villalón, Carlos M; Ferrari, Michel D

    2016-09-01

    Migraine is a common episodic neurovascular brain disorder associated with increased risk of cardio- and cerebrovascular ischemia. Migraine headache is likely caused by activation of the trigeminovascular system and release of calcitonin gene-related peptide (CGRP). Monoclonal antibodies against CGRP or its receptor are currently being evaluated for the prevention of migraine attacks. Preliminary efficacy data are promising. However, because CGRP may act as a vasodilatory safeguard during cerebral and cardiac ischemia, CGRP blockade could transform transient mild ischemic events into full-blown infarcts. Here, we review the cerebro- and cardiovascular risks that might be associated with CGRP blockade and which clinical and preclinical studies should be conducted to better assess the potential safety issues of this new promising class of drug. PMID:27338837

  14. New drugs in migraine treatment and prophylaxis

    DEFF Research Database (Denmark)

    Edvinsson, Lars; Linde, Mattias

    2010-01-01

    Although the triptan drugs provide effective relief from migraine for many patients, a substantial number of affected individuals are unresponsive to these compounds, and such therapy can also lead to a range of adverse effects. Telcagepant represents a new class of antimigraine drug-the calcitonin...... of triptans. Comparisons with triptans in clinical trials for acute treatment of migraine attacks revealed clinical effects similar to those of triptans but better than those of placebo. Telcagepant might provide hope for those who have a poor response to, or are unable to use, older drugs. In patients who...... need prophylaxis because of frequent attacks of migraine, topiramate is a first-line drug for migraine prevention inmany countries; it is generally safe and reasonably well tolerated. Data suggest that topiramate could aid reversion of chronic migraine to episodic migraine....

  15. [Botulinum toxin type A in headache treatment : Established and experimental indications].

    Science.gov (United States)

    Gaul, C; Holle-Lee, D; Straube, A

    2016-08-01

    In recent years botulinum toxin type A has been used increasingly more in the treatment of specific headache disorders. Especially regarding chronic migraine with and without combined medication overuse, convincing randomized studies have proven the efficacy of this treatment option and have led to approval for this indication. Regarding other headache entities, such as episodic migraine, tension-type headache, trigeminal autonomic cephalalgia (TAC), neuralgic, neuropathic and myofascial pain, currently available scientific data on the efficacy of botulinum toxin type A are scarce and often ambiguous. The exact underlying mechanisms of the influence of botulinum toxin type A on the pathophysiology of headache are not completely clear but an influence on the release of calcitonin gene-related peptide (CGRP) seems to play a crucial role. This article summarizes the most important studies as well as experiences of treatment with botulinum toxin type A regarding different headache entities. PMID:27300190

  16. Thyroid c-cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Miller, Debra L; Styer, Eloise L; Stobaeus, Janeen K; Norton, Terry M

    2002-12-01

    A 3-yr-old African pygmy hedgehog (Atelerix albiventris) was submitted with dysphagia, weight loss, and tetraparesis. A palpable mass was found on the ventral neck. Histologic examination revealed replacement of the thyroid gland by a highly cellular, expansile, and infiltrative mass composed of lobules of polygonal cells separated by fine fibrovascular septa. Examination of ultrathin sections revealed tumor cells with few to many dense-core neuroendocrine granules, approximately 100-200 nm in diameter, and stromal amyloid. Immunohistochemical stains were positive for neuron-specific enolase. Only rare cells had positive immunohistochemical staining for calcitonin. Findings are consistent with a neuroendocrine tumor of C-cell origin. This is the first report of a C-cell carcinoma in a hedgehog. PMID:12564541

  17. Emerging migraine treatments and drug targets

    DEFF Research Database (Denmark)

    Olesen, Jes; Ashina, Messoud

    2011-01-01

    Migraine has a 1-year prevalence of 10% and high socioeconomic costs. Despite recent drug developments, there is a huge unmet need for better pharmacotherapy. In this review we discuss promising anti-migraine strategies such as calcitonin gene-related peptide (CGRP) receptor antagonists and 5......-hydroxytrypamine (5-HT)(1F) receptor agonists, which are in late-stage development. Nitric oxide antagonists are also in development. New forms of administration of sumatriptan might improve efficacy and reduce side effects. Botulinum toxin A has recently been approved for the prophylaxis of chronic migraine....... Tonabersat, a cortical spreading depression inhibitor, has shown efficacy in the prophylaxis of migraine with aura. Several new drug targets such as nitric oxide synthase, the 5-HT(1D) receptor, the prostanoid receptors EP(2) and EP(4), and the pituitary adenylate cyclase receptor PAC1 await development...

  18. 女性偏头脑相关因素及西比灵的防治研究%Prevention and Treatment of Migraine byFlunarizine (Sibelium)and the Related Factors

    Institute of Scientific and Technical Information of China (English)

    方燕南; 余剑; 林建雯; 李玲; 黄海威; 黄如训

    2001-01-01

    Objective To observe the relationship of sibelium between vasodilatlting and vasoconstricting factors, and the treating and preoeating effect of sibelium on migraine in women Methods 60 women wre randomly divided into the xueshuantong group( n= 30) and sibelium group(n = 30). We compared the therapeutic effect in the two groups, detected endothelins(ET) and calcitonin gene - related peptide (CGRP) in blood before and after treatment Results In sibelium group, the concentration of CGRP after treatment was lower than that before treatment.Sibelium lightened the extent of heodoche, reduced the duration of headache( both effciency rate of 93% ). Xueshuantong could only lighten the degree of headache(effuctive rate: 70% ). Conclusion Sibelium could control the attack of migraine in women without obvious side effect.

  19. Postmenopausal hormone replacement therapy--clinical implications

    DEFF Research Database (Denmark)

    Ravn, S H; Rosenberg, J; Bostofte, E

    1994-01-01

    in the urogenital tract. Women at risk of osteoporosis will benefit from hormone replacement therapy. The treatment should start as soon after menopause as possible and it is possible that it should be maintained for life. The treatment may be supplemented with extra calcium intake, vitamin D, and maybe calcitonin....... Physical activity should be promoted, and cigarette smoking reduced if possible. Women at risk of cardiovascular disease will also benefit from hormone replacement therapy. There is overwhelming evidence that hormone therapy will protect against both coronary heart disease and stroke......, and there is no increased risk of venous thrombosis or hypertension. A disadvantage of hormone replacement therapy is an increased risk of forming gall-bladder stones and undergoing cholecystectomy. Unopposed estrogen therapy gives a higher incidence of endometrial cancer in women with an intact uterus...

  20. Role of thallium-201 total-body scintigraphy in follow-up of thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A.; Delprat, C.C.; Marcuse, H.R.; de Vijlder, J.J.

    1986-12-01

    To evaluate the reliability of total-body scintigraphy using (/sup 201/Tl)chloride in postoperative follow-up of thyroid carcinoma, this procedure was performed in 326 patients after total thyroidectomy for thyroid carcinoma. The results were compared with those of 131I scintigraphy and thyroglobulin assays. /sup 201/Tl total-body scintigraphy was found to have the greatest sensitivity (94%), whereas /sup 131/I scintigraphy had the highest specificity (99%). It is shown that /sup 201/Tl total-body scintigraphy is a useful procedure in follow-up of thyroid cancer, however, the combination of parameters provides the greatest reliability. In medullary thyroid carcinoma, which is usually /sup 131/I negative, /sup 201/Tl total-body scintigraphy can be of great value for the localization of metastases which are indicated by elevated serum levels of calcitonin and carcinoembryonic antigen.

  1. The role of Cdk5 in neuroendocrine thyroid cancer.

    Science.gov (United States)

    Pozo, Karine; Castro-Rivera, Emely; Tan, Chunfeng; Plattner, Florian; Schwach, Gert; Siegl, Veronika; Meyer, Douglas; Guo, Ailan; Gundara, Justin; Mettlach, Gabriel; Richer, Edmond; Guevara, Jonathan A; Ning, Li; Gupta, Anjali; Hao, Guiyang; Tsai, Li-Huei; Sun, Xiankai; Antich, Pietro; Sidhu, Stanley; Robinson, Bruce G; Chen, Herbert; Nwariaku, Fiemu E; Pfragner, Roswitha; Richardson, James A; Bibb, James A

    2013-10-14

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from calcitonin-secreting parafollicular cells, or C cells. We found that Cdk5 and its cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity promotes MTC proliferation. A conditional MTC mouse model was generated and corroborated the role of aberrant Cdk5 activation in MTC. C cell-specific overexpression of p25 caused rapid C cell hyperplasia leading to lethal MTC, which was arrested by repressing p25 overexpression. A comparative phosphoproteomic screen between proliferating and arrested MTC identified the retinoblastoma protein (Rb) as a crucial Cdk5 downstream target. Prevention of Rb phosphorylation at Ser807/Ser811 attenuated MTC proliferation. These findings implicate Cdk5 signaling via Rb as critical to MTC tumorigenesis and progression. PMID:24135281

  2. Metabolic cleavage of cell-penetrating peptides in contact with epithelial models

    DEFF Research Database (Denmark)

    Tréhin, Rachel; Nielsen, Hanne Mørck; Jahnke, Heinz-Georg;

    2004-01-01

    We assessed the metabolic degradation kinetics and cleavage patterns of some selected CPP (cell-penetrating peptides) after incubation with confluent epithelial models. Synthesis of N-terminal CF [5(6)-carboxyfluorescein]-labelled CPP, namely hCT (human calcitonin)-derived sequences, Tat(47-57) and...... penetratin(43-58), was through Fmoc (fluoren-9-ylmethoxycarbonyl) chemistry. Metabolic degradation kinetics of the tested CPP in contact with three cell-cultured epithelial models, MDCK (Madin-Darby canine kidney), Calu-3 and TR146, was evaluated by reversed-phase HPLC. Identification of the resulting...... models and the CPP. The Calu-3 model exhibited the highest proteolytic activity. The patterns of metabolic cleavage of hCT(9-32) were similar in all three models. Initial cleavage of this peptide occurred at the N-terminal domain, possibly by endopeptidase activity yielding both the N- and the C...

  3. Study on osteogenesis promoted by low sound pressure level infrasound in vivo and some underlying mechanisms.

    Science.gov (United States)

    Long, Hua; Zheng, Liheng; Gomes, Fernando Cardoso; Zhang, Jinhui; Mou, Xiang; Yuan, Hua

    2013-09-01

    To clarify the effects of low sound pressure level (LSPL) infrasound on local bone turnover and explore its underlying mechanisms, femoral defected rats were stabilized with a single-side external fixator. After exposure to LSPL infrasound for 30min twice everyday for 6 weeks, the pertinent features of bone healing were assessed by radiography, peripheral quantitative computerized tomography (pQCT), histology and immunofluorescence assay. Infrasound group showed a more consecutive and smoother process of fracture healing and modeling in radiographs and histomorphology. It also showed significantly higher average bone mineral content (BMC) and bone mineral density (BMD). Immunofluorescence showed increased expression of calcitonin gene related peptide (CGRP) and decreased Neuropeptide Y (NPY) innervation in microenvironment. The results suggested the osteogenesis promotion effects of LSPL infrasound in vivo. Neuro-osteogenic network in local microenvironment was probably one target mediating infrasonic osteogenesis, which might provide new strategy to accelerate bone healing and remodeling. PMID:23770453

  4. Effects of Compound Rhubarb Pill on Plasma D-lactate and Procalctionin Expressions in Patients with Sepsis%复方大黄片对脓毒症患者血浆 D-乳酸及前降钙素表达的影响

    Institute of Scientific and Technical Information of China (English)

    施伟民

    2014-01-01

    目的:研究复方大黄片对脓毒症患者血浆D-乳酸及前降钙素表达的影响。方法:2013年2月-2014年2月入住我院外科的脓毒症患者55例,分为大黄治疗组(30例)和非大黄治疗组(25例)。大黄治疗组给予复方大黄片3g/次,1次/8h服用,附带常规治疗,常规治疗包括抗生素、舒普深、特治星、泰能;保证水和电解质以及营养的正常供给。非大黄治疗组只给予常规治疗。两组病例治疗前和治疗后1d、4d测定血浆D-乳酸和前降钙素水平变化情况。结果:治疗前大黄治疗组患者的血浆D-乳酸水平和前降钙素水平与非大黄治疗组比较,差异无显著性( P>0.05);治疗1d、4d后血浆D-乳酸水平大黄治疗组明显低于非大黄治疗组(P<0.05)。治疗1d后两组血浆前降钙素水平无明显差异( P>0.05)。治疗4d后两组病例的血浆前降钙素水平比较结果中,大黄治疗组明显低于非大黄治疗组,差异存在显著性(P<0.01)。结论:复方大黄片能改善脓毒症患者的肠道通透性,减少细菌易位。%Objective:To study the compound big porn plasma D-lactic acid in patients with sepsis and the former ex-press the effect of calcitonin .Methods:February 2013 to February 2014 ,our hospital surgical of 55 patients with sep-sis ,rhubarb treatment group (30 cases) and non rhubarb treatment group (25 cases) .Rhubarb treatment group given compound rhubarb ,3g/second ,1/8h ,with routine therapy and routine therapy including antibiotics ,shope deep ,Sin-gapore and Thailand can cure;assure the normal supply of water and electrolyte ,and nutrition .The rhubarb treatment group given conventional treatment .Two groups of cases before and after treatment 1d ,4d to determine patients plasma D-lactic acid and calcitonin level changes .Results:The treatment group before treatment the patient’s level of plasma D-lactic acid and calcitonin level before ,with

  5. Oral delivery of proteins: progress and prognostication.

    Science.gov (United States)

    Shah, Rakhi B; Ahsan, Fakhrul; Khan, Mansoor A

    2002-01-01

    The delivery of proteins has gained momentum with the development of biotechnology sector that provided large-scale availability of therapeutic proteins. The availability is mostly due to the advances in recombinant DNA technology. The low oral bioavailability, however, continues to be a problem for several proteins because of their large molecular size, low permeation through biological membranes, and susceptibility to molecular changes in both biological and physical environments. The demand for effective delivery of proteins by the oral route has brought a tremendous thrust in recent years both in the scope and complexity of drug delivery technology. The important therapeutic proteins and peptides being explored for oral delivery include insulin, calcitonin, interferons, human growth hormone, glucagons, gonadotropin-releasing hormones, enkephalins, vaccines, enzymes, hormone analogs, and enzyme inhibitors. This article reviews the progress in oral delivery of these proteins, provides comments on the strategies to improve their oral bioavailability, and highlights their current market trends. PMID:12197608

  6. The blood-brain barrier in migraine treatment

    DEFF Research Database (Denmark)

    Edvinsson, L; Tfelt-Hansen, P

    2008-01-01

    to the central nervous system by diffusion, whereas other substances can cross the BBB by carrier-mediated influx transport, receptor-mediated transcytosis and absorptive-mediated transcytosis. Studies of drugs relevant to migraine pathophysiology and treatment have been examined with the pressurized......Salient aspects of the anatomy and function of the blood-barrier barrier (BBB) are reviewed in relation to migraine pathophysiology and treatment. The main function of the BBB is to limit the access of circulating substances to the neuropile. Smaller lipophilic substances have some access...... with special emphasize on the triptans and calcitonin gene-related peptide (CGRP). The human experimental headache model, especially the use of glycerol trinitrate (the nitric oxide model), and experiences with CGRP administrations utilize the systemic administration of the agonists with effects on other...

  7. Migraine.

    Science.gov (United States)

    Peck, K R; Johnson, Y L; Smitherman, T A

    2016-01-01

    This chapter presents an overview of migraine epidemiology and mechanisms. Migraine is a common and disabling neurologic disorder characterized by episodic attacks of severe head pain and other symptoms, including interference with activity, nausea, and sensitivity to light and sound. A number of risk factors for migraine onset and progression have been identified, including the presence of comorbid disorders and overuse of acute headache medications. Though the pathophysiology of migraine is complex and incompletely understood, advances in genetics research and clinical trials methodology offer promise for better understanding the underlying pathophysiologic mechanisms. These advances presently center on genomewide studies, development of antibodies targeting calcitonin gene-related peptide, and understanding the psychologic mechanisms that underlie the efficacy of some interventions. Studies of both pharmacologic and behavioral interventions for migraine and its common comorbidities also offer promise for understanding the neuroepidemiologic mechanisms of migraine. Clinical trials relevant to these mechanisms are reviewed, and methodologic considerations for future trials are discussed. PMID:27637964

  8. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    Science.gov (United States)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  9. Peptide Synthesis through Cell-Free Expression of Fusion Proteins Incorporating Modified Amino Acids as Latent Cleavage Sites for Peptide Release.

    Science.gov (United States)

    Liutkus, Mantas; Fraser, Samuel A; Caron, Karine; Stigers, Dannon J; Easton, Christopher J

    2016-05-17

    Chlorinated analogues of Leu and Ile are incorporated during cell-free expression of peptides fused to protein, by exploiting the promiscuity of the natural biosynthetic machinery. They then act as sites for clean and efficient release of the peptides simply by brief heat treatment. Dehydro analogues of Leu and Ile are similarly incorporated as latent sites for peptide release through treatment with iodine under cold conditions. These protocols complement enzyme-catalyzed methods and have been used to prepare calcitonin, gastrin-releasing peptide, cholecystokinin-7, and prolactin-releasing peptide prohormones, as well as analogues substituted with unusual amino acids, thus illustrating their practical utility as alternatives to more traditional chemical peptide synthesis. PMID:26918308

  10. Topical non-peptide antagonists of sensory neurotransmitters substance P and CGRP do not modify patch test and prick test reactions

    DEFF Research Database (Denmark)

    Wallengren, Joanna; Edvinsson, Lars

    2014-01-01

    developed. Their effect on the skin barrier was measured in terms of transepidermal water loss (TEWL) while permeation was calculated using permeation coefficients. Patch tests in patients allergic to nickel and prick test reactions to histamine were used as models. None of the treatments increased TEWL...... vasoconstriction in the skin but did not change the infiltration of nickel reactions. None of the treatments influenced the nickel patch test induced pruritus. The data suggest that the topical application of non-peptide antagonists penetrates the skin but does not inhibit contact dermatitis or pruritus.......Immunologic responses in the skin can be modulated by such neurotransmitters of sensory nerve fibers as substance P (SP) and calcitonin gene-related peptide (CGRP). The first-generation receptor antagonists were peptides with large molecules and had to be injected intracutaneously. The aim...

  11. A Case Report of Multiple Endocrine Neoplasia Type IIa Associated with Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2013-10-01

    Full Text Available Introduction: Multiple endocrine neoplasia type IIa (MEN IIa is an autosomal dominant syn-drome characterized bypheochromocytoma ,medullary thyroid carcinoma and hyperparathy-roidism. Pheochromocytoma approximately occurs in 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and becomes manifest like Cushing syndrome,although it is very rare. Case Report: We report a 26-year-old woman patient with severe muscle weakness, skin le-sions in extremity, hypertension, new onset diabetes and in the laboratory data hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. Conclusion: In the patients with hypertension, new onset diabetes and hypokalemia Cushing syndrome and pheochromocytoma should always be ruled out. (Sci J Hamadan Univ Med Sci 2013; 20 (3:260-265

  12. The future of osteoarthritis therapeutics: emerging biological therapy.

    Science.gov (United States)

    Mobasheri, A

    2013-12-01

    Biological therapy is a thriving area of research and development, and is well established for chronic forms of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, there is no clinically validated biological therapy for osteoarthritis (OA). Chronic forms of OA are increasingly viewed as an inflammatory disease. OA was largely regarded as a "wear and tear disease". However, the disease is now believed to involve "low grade" inflammation and the growth of blood vessels and nerves from the subchondral bone into articular cartilage. This realization has focused research effort on the development and evaluation of biological therapy that targets proinflammatory mediators, angiogenic factors and cytokines in articular cartilage, subchondral bone and synovium in chronic forms of OA. This review article provides an overview of emerging biological therapy for OA, and discusses recent molecular targets implicated in angiogenesis and neurogenesis and progress with antibody-based therapy, calcitonin, and kartogenin, the small molecule stimulator of chondrogenesis. PMID:24170255

  13. Migraine pathogenesis and state of pharmacological treatment options

    Directory of Open Access Journals (Sweden)

    Goadsby Peter J

    2009-11-01

    Full Text Available Abstract Migraine is a largely inherited disorder of the brain characterized by a complex, but stereotypical, dysfunction of sensory processing. Often the most obvious clinical symptom is head pain, but non-headache symptoms such as photophobia, phonophobia and nausea are clearly part of the typical presentation. This review discusses the current pathophysiological concepts of migraine and migraine aura, such as a possible brainstem dysfunction and cortical spreading depression. Acute and preventive migraine treatment approaches are briefly covered with a focus on shortcomings of the currently available treatment options. A number of different receptors, such as calcitonin gene-related peptide (CGRP, TRPV1 and glutamate receptors, are currently being targeted by potential novel migraine therapeutics. The prospects of this research are exciting and are likely to improve patient care.

  14. In vitro Leishmania major promastigote-induced macrophage migration is modulated by sensory and autonomic neuropeptides

    DEFF Research Database (Denmark)

    Ahmed, A A; Wahbi, A; Nordlind, K;

    1998-01-01

    the chemotactic activities of live, killed and sonicated Leishmania major promastigotes and of the promastigote culture supernatant as well as the L. major surface protease gp63 towards a murine macrophage cell line, Raw 264.7, were investigated, using the Boyden technique. The sensory neuropeptides SOM, CGRP...... and SP, and the autonomic neuropeptides VIP and NPY, were also investigated for possible modulatory effects on this chemotaxis, using the living promastigotes. Living promastigotes were the most efficient attractants for macrophages compared with other forms of the parasites. Prior incubation...... effect of calcitonin gene-related peptide was found at high concentrations, 10(-5) and 10(-6) M. Vasoactive intestinal peptide stimulated macrophage chemotactic activity at both a high, 10(-5) M, and at a low, 10(-9) M, concentration, the same concentration at which neuropeptide Y exerted its maximum...

  15. Role of neuropeptides in cardiomyopathies.

    Science.gov (United States)

    Dvorakova, Magdalena Chottova; Kruzliak, Peter; Rabkin, Simon W

    2014-11-01

    The role of neuropeptides in cardiomyopathy-associated heart failure has been garnering more attention. Several neuropeptides--Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP) and their receptors have been studied in the various types of cardiomyopathies. The data indicate associations with the strength of the association varying depending on the kind of neuropeptide and the nature of the cardiomyopathy--diabetic, ischemic, inflammatory, stress-induced or restrictive cardiomyopathy. Several neuropeptides appear to alter regulation of genes involved in heart failure. Demonstration of an association is an essential first step in proving causality or establishing a role for a factor in a disease. Understanding the complexity of neuropeptide function should be helpful in establishing new or optimal therapeutic strategies for the treatment of heart failure in cardiomyopathies.

  16. Determination of specific neuropeptides modulation time course in a rat model of osteoarthritis pain by liquid chromatography ion trap mass spectrometry.

    Science.gov (United States)

    Ferland, Catherine E; Pailleux, Floriane; Vachon, Pascal; Beaudry, Francis

    2011-12-01

    Animal models are useful to evaluate pharmacological therapies to alleviate joint pain. The present study characterized central neuropeptides modulation in the monoiodoacetate (MIA) rat model. Animals receiving a single 3mg MIA injection were euthanized at 3, 7, 14, 21 and 28 days post injection. Spinal cords were analyzed by liquid chromatography ion trap mass spectrometry. Up-regulations of the calcitonin gene-related peptide and substance P were observed starting on days 7 and 28 respectively, whereas big dynorphin(₁₋₃₂) content decreased significantly on day 14 in comparison to control animals (P<0.05). Preclinical drug evaluations using this model should be conducted between 7 and 21 days post injection when the lesions resemble most to human osteoarthritis.

  17. 骨折愈合相关神经肽的研究进展

    Institute of Scientific and Technical Information of China (English)

    李宏键; 徐世莲

    2007-01-01

    神经肽(neuropeptide,NP)是在骨折创伤时由感觉神经释放,参与组织细胞增殖、分化的调控。目前发现骨组织中含有的神经肽有降钙素基因相关肽(calcitonin gene-related peptide,CGRP)、P物质(substance P,SP)、血管活性肠肽(vasoactive intestinal polypeptide,VIP)、神经肽Y(neuropeptide Y,NPY)和腺苷酸环化酶激活肽(adenylate cyclase activating polypeptide,ACAP)、蛋白基因产物(protein geneproduct 9.5,PGP9.5)和酪氨酸羟化酶(tyrosine hydroxylase,TH)等。

  18. Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment.

    Science.gov (United States)

    Hegbrant, J; Thysell, H; Ekman, R

    1992-01-01

    The fasting plasma levels of 10 vasoactive regulatory peptides were measured by radioimmunoassay in 23 stable patients with chronic renal failure receiving regular hemodialysis treatment (RDT) and compared with those of healthy controls. The plasma concentrations of arginine vasopressin, atrial natriuretic peptide, beta-endorphin, methionine-enkephalin, motilin, neuropeptide Y, substance P, and vasoactive intestinal peptide were increased. The plasma level of calcitonin gene-related peptide was not statistically different from that of the controls. The plasma concentration of gamma 2-melanocyte-stimulating hormone was lowered in the RDT-patients. The arterial blood pressure correlated with the plasma levels of motilin and neuropeptide Y. We conclude that patients with chronic renal failure receiving RDT have increased concentrations of 8 out of 10 measured vasoactive regulatory peptides. The elevated levels of vasoactive peptides may contribute to the adaptation of the cardiovascular system to impaired renal function.

  19. Hyalinizing trabecular adenoma--a case report with FNAC histologic, MIB-1 proliferative index and immunohistochemical findings.

    Science.gov (United States)

    Karak, A K; Sahoo, M; Bhatnagar, D

    1998-10-01

    Hyalinizing trabecular adenoma is a recently described benign thyroid tumor, almost exclusively occurring in females. The morphological features of this entity overlap with both papillary and medullary carcinoma to varying extent. This, in turn, creates a situation of serious diagnostic pitfall particularly for a false positive diagnosis of papillary carcinoma in fine needle aspiration (FNA) cytology. False consideration of medullary carcinoma is also possible by the unwary especially if staining for Congo red and/or immunostaining for calcitonin is not resorted to. At histologic level, the distinctive architectural pattern is however of great help and thus poses a much lesser danger of misdiagnosis. We relate here our experience in a recently encountered case of hyalinizing trabecular adenoma and describe detailed FNA cytologic and histologic findings along with immunohistochemical profile using a panel of eight monoclonal antibodies. The tumor proliferative potential has also been assessed using MIB-1 (Ki-67) immunostaining. The various pros and cons of diagnostic pitfalls are discussed. PMID:9866913

  20. Neutron diffraction studies of amphipathic helices in phospholipid bilayers

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, J.P.; Gilchrist, P.J. [Univ. of Edinburgh (United Kingdom); Duff, K.C. [Univ. of Edinburgh Medical School (United Kingdom); Saxena, A.M. [Brookhaven National Laboratory, Upton, NY (United States)

    1994-12-31

    The structural feature which is thought to facilitate the interaction of many peptides with phospholipid bilayers is the ability to fold into an amphipathic helix. In most cases the exact location and orientation of this helix with respect to the membrane is not known, and may vary with factors such as pH and phospholipid content of the bilayer. The growing interest in this area is stimulated by indications that similar interactions can contribute to the binding of certain hormones to their cell-surface receptors. We have been using the techniques of neutron diffraction from stacked phospholipid bilayers in an attempt to investigate this phenomenon with a number of membrane-active peptides. Here we report some of our findings with three of these: the bee venom melittin; the hormone calcitonin; and a synthetic peptide representing the ion channel fragment of influenza A M2 protein.

  1. 降钙素预防激素性股骨头坏死的实验研究

    Institute of Scientific and Technical Information of China (English)

    甘霖; 韩树峰

    2013-01-01

      Objective According to the theory of glucocorticoid-induced avascular necrosis of the osteoporosis, experimental research and treatment of osteoporosis drug salmon calcitonin for glucocorticoid-induced avascular necrosis of the early prevention, and to explore its mechanism. Methods 18 healthy adult SD rats were randomly divided into three groups, Group A:horse serum+dexamethasone;group B:horse serum salmon+dexamethasone+Salmon calcitonin+Compound Calcium Amino Acid Chelate Capsules;C groups:blank control group. A group was injected horse serum 20 ml/(kg•times) by tail vein, twice in total, and interval of 3 weeks between the two injection.Two weeks after the second round of horse serum injection, A group were given gastric lavage with dexamethasone injection for three days, 20 mg/kg•day. In addition to the part same as group A, group B in another horse serum 1 day intramuscular injection salmon calcitonin 10 u/kg•d, and Compound Calcium Amino Acid Chelate Capsules lavage 250 mg/kg•d;Blank control group in the corresponding time same parts injection and gastric same amount of saline solution. Results-Group A‘s femoral head compared with group B has more obvious bone cell necrosis, medullary cavity hematopoietic cells have decreased significantly, the activity of A and B group were osteonecrosis after repair, but group B more clearly. Conclusion Salmon calcitonin Compound Calcium Amino Acid Chelate Capsules, for glucocorticoid-induced avascular necrosis of the early have certain prevention and promote its repair effect.%  目的根据激素性股骨头坏死的骨质疏松理论,实验性研究治疗骨质疏松药物鲑鱼降钙素对于早期激素性股骨头坏死的预防作用,并探讨其机制。方法将18只成年健康SD大鼠随机分为3组,A组:马血清+地塞米松,B组:马血清+地塞米松+鲑鱼降钙素+乐力,C组:空白对照组。A组经尾静脉注射马血清20 mL/(kg·次),共两次,间隔3周,

  2. IUPHAR Review 1

    DEFF Research Database (Denmark)

    Harmar, Anthony J; Fahrenkrug, Jan; Gozes, Illana;

    2012-01-01

    (GHRH). VIP and PACAP exert their actions through three G protein-coupled receptors (GPCRs) - PAC(1) , VPAC(1) and VPAC(2) - belonging to class B (also referred to as class II, or secretin receptor-like GPCRs). This family comprises receptors for all peptides structurally related to VIP and PACAP......, and also receptors for parathyroid hormone, corticotropin-releasing factor, calcitonin and related peptides. PAC(1) receptors are selective for PACAP, whereas VPAC(1) and VPAC(2 ) respond to both VIP and PACAP with high affinity. VIP and PACAP play diverse and important roles in the CNS, with functions...... in the control of circadian rhythms, learning and memory, anxiety and responses to stress and brain injury. Recent genetic studies also implicate the VPAC(2) receptor in susceptibility to schizophrenia and the PAC(1) receptor in post-traumatic stress disorder. In the periphery, VIP and PACAP play important roles...

  3. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia.

    Science.gov (United States)

    Roman, Carolyn W; Derkach, Victor A; Palmiter, Richard D

    2016-06-15

    The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRP(PBN)) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRP(PBN) neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRP(PBN) neurons to promote anorexia.

  4. Analysis of origin and growth of the thyroid gland in zebrafish.

    Science.gov (United States)

    Alt, Burkhard; Reibe, Saskia; Feitosa, Natalia M; Elsalini, Osama A; Wendl, Thomas; Rohr, Klaus B

    2006-07-01

    The zebrafish thyroid gland shows a unique pattern of growth as a differentiated endocrine gland. Here, we analyze the onset of differentiation, the contribution of lineages, and the mode of growth of this gland. The expression of genes involved in hormone production and the establishment of epithelial polarity show that differentiation into a first thyroid follicle takes place early during embryonic development. Thyroid follicular tissue then grows along the pharyngeal midline, initially independently of thyroid stimulating hormone. Lineage analysis reveals that thyroid follicle cells are exclusively recruited from the pharyngeal endoderm. The ultimobranchial bodies that merge with the thyroid in mammals form separate glands in zebrafish as visualized by calcitonin precursor gene expression. Mosaic analysis suggests that the first thyroid follicle differentiating at 55 hours postfertilization corresponds later to the most anterior follicle and that new follicles are added caudally.

  5. Glukokortikoid-induzierte Osteoporose

    Directory of Open Access Journals (Sweden)

    Gasser RW

    2001-01-01

    Full Text Available Die Osteoporose ist eine gravierende Nebenwirkung einer langfristigen Glukokortikoid-Therapie. Steroide wirken sich negativ auf den Knochenstoffwechsel aus, vorwiegend durch Hemmung der Osteoblastenaktivität, durch Verminderung der enteralen Kalziumabsorption, durch Steigerung der renalen Kalziumausscheidung sowie durch einen steroidinduzierten Hypogonadismus. Eine langfristige Steroidtherapie führt zu einer Abnahme der Knochendichte und in der Folge zu einer erhöhten Frakturinzidenz. Die Glukokortikoid-induzierte Osteoporose ist potentiell reversibel, daher sind präventive und therapeutische Maßnahmen bei jeder langfristigen Glukokortikoid-Therapie (5 mg oder mehr Prednison-Äquivalent über 3 oder mehr Monate erforderlich. Bisphosphonate sind die derzeit wirksamsten Medikamente in Prävention und Therapie der Glukokortikoid-induzierten Osteoporose. Eine Basistherapie mit Kalzium und Vitamin D sollte grundsätzlich erfolgen. Effektiv ist eine Hormonersatztherapie bei postmenopausalen Frauen. Adjuvant stehen Vitamin D-Metabolite und Calcitonin zur Verfügung.

  6. Thyroid Cancer in children and adolescents

    International Nuclear Information System (INIS)

    24 cases were revised, of patient with thyroid tumors in the period understood between 1983 and 1995. Of these tumors 14 were papillars, 3 medullar, 3 children with high levels of thyro calcitonine, 2 with follicular adenomas, a boy with hyperplasia and a doubtful cytology to the one who two years later it was made a total thyroidectomy. Most of the patients were bigger than the 10 years, globally there was not great difference in the distribution for sex, being lightly bigger the number of patient of feminine sex; in the medullar, the relationship was of 2:1 feminine: Masculine, similar to that reported in the literature. To the date, they are alive and without illness 12 patients; 3 evolve with lung metastasis, 2 (with lung metastasis) they abandoned the controls, 3 died with illness and 1 present metastasis and cardiac illness. Iodine131 was used in eleven patients

  7. Codon Y791F mutations in a large kindred: is prophylactic thyroidectomy always indicated?

    DEFF Research Database (Denmark)

    Vestergaard, Peter; Vestergaard, Else Marie; Brockstedt, Helle;

    2007-01-01

    BACKGROUND: RET proto-oncogene mutations are associated with medullary thyroid carcinomas usually requiring preventive thyroidectomy in gene carriers. We present a large kindred with the Y791F mutation in the RET proto-oncogene that did not have medullary thyroid carcinomas. PATIENTS AND METHODS......: Eight members of a Danish family with the Y791F mutation participated. All gene carriers underwent pentagastrin testing, and measurements of serum calcitonin. In the index person, exons 10, 11, and 13-16 of the RET proto-oncogene were screened. In the rest of the individuals only exon 13 was analysed......-gene carriers (0.55 +/- 0.86 pmol/l, n = 6, 2 P = 0.29). None showed signs of primary hyperparathyroidism or phaeochromocytoma. CONCLUSIONS: The Y791F RET proto-oncogene mutation may have a low penetrance. In selected cases, prophylactic thyroidectomy may be replaced by watchful waiting with repeated...

  8. Immunohistochemical study on distribution of endocrine cells in gastrointestinal tract of flower fish (Pseudophoxinus antalyae)

    Institute of Scientific and Technical Information of China (English)

    Kenan (C)inar; Nurgül (S)enol; M Rü(s)tü (O)zen

    2006-01-01

    AIM:To detect distribution and relative frequency of endocrine cells in gastrointestinal tract of flower fish (Pseudophoxinus antalyae ).METHOIS:The intestinal tract of flower fish was divided into four portions from proximal to distal;the enlarged area after oesophagus and anterior, middle and posterior intestine. Immunohistochemical method using the peroxidase anti-peroxidase complex was employed.All antisera between four portions of flower fish were compared using ANOVA.RESULTS:Eleven types of gut endocrine cells were determined; they were immunoreactive for calcitonin gene related peptide, substance P, vasoactive intestinal peptide, bombesin, somatostatin-14, secretin, TrkA, TrkB,TrkC, neurotensin, neuropeptide Y, which were found in almost all portions of the gastrointestinal tract.CONCLUSION:The regional distribution and relative frequency of immunoreactive cells in the flower fish,Pseudophoxinus antalyae, are essentially similar to those of other fish.

  9. Genetically and functionally defined NTS to PBN brain circuits mediating anorexia

    Science.gov (United States)

    Roman, Carolyn W.; Derkach, Victor A.; Palmiter, Richard D.

    2016-01-01

    The central nervous system controls food consumption to maintain metabolic homoeostasis. In response to a meal, visceral signals from the gut activate neurons in the nucleus of the solitary tract (NTS) via the vagus nerve. These NTS neurons then excite brain regions known to mediate feeding behaviour, such as the lateral parabrachial nucleus (PBN). We previously described a neural circuit for appetite suppression involving calcitonin gene-related protein (CGRP)-expressing PBN (CGRPPBN) neurons; however, the molecular identity of the inputs to these neurons was not established. Here we identify cholecystokinin (CCK) and noradrenergic, dopamine β-hydroxylase (DBH)-expressing NTS neurons as two separate populations that directly excite CGRPPBN neurons. When these NTS neurons are activated using optogenetic or chemogenetic methods, food intake decreases and with chronic stimulation mice lose body weight. Our optogenetic results reveal that CCK and DBH neurons in the NTS directly engage CGRPPBN neurons to promote anorexia. PMID:27301688

  10. 应用A549细胞单层模型研究蛋白多肽类药物肺部吸收的特性%Transport of proteins and peptides across human cultured alveolar A549 cell monolayers

    Institute of Scientific and Technical Information of China (English)

    王智瑛; 张悦; 张强

    2004-01-01

    Aim An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway peptides or proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium in vivo. Methods Human lung adenocareinoma A549 cells formed continuous monolayers with growing polycarbonate filters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out after 6 days in culture. The transport of peptides or proteins with MW 3 400 - 22 000 was studied in cultured human lung adenocareinoma A549 cell monolayers at different conditions. Results The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2×10-6 to 5×10-6 cm·s-1 and exhibited good inverse correlation with molecule weight. No concentration, direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Papp of rhGH in the BA direction (2.25×10-6 cm·s-1) was significantly less than that in the reverse direction. ThePapp values of rhGH were concentration and temperature independent in the AB direction. Conclusion These findings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin, and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers via a paracellular pathway by passive diffusion mechanism.

  11. Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice.

    Directory of Open Access Journals (Sweden)

    Manyu Li

    Full Text Available Asthma is a chronic inflammatory disease affecting the lung, characterized by breathing difficulty during an attack following exposure to an environmental trigger. Calcitonin gene-related peptide (CGRP is a neuropeptide that may have a pathological role in asthma. The CGRP receptor is comprised of two components, which include the G-protein coupled receptor, calcitonin receptor-like receptor (CLR, and receptor activity-modifying protein 1 (RAMP1. RAMPs, including RAMP1, mediate ligand specificity in addition to aiding in the localization of receptors to the cell surface. Since there has been some controversy regarding the effect of CGRP on asthma, we sought to determine the effect of CGRP signaling ablation in an animal model of asthma. Using gene-targeting techniques, we generated mice deficient for RAMP1 by excising exon 3. After determining that these mice are viable and overtly normal, we sensitized the animals to ovalbumin prior to assessing airway resistance and inflammation after methacholine challenge. We found that mice lacking RAMP1 had reduced airway resistance and inflammation compared to wildtype animals. Additionally, we found that a 50% reduction of CLR, the G-protein receptor component of the CGRP receptor, also ameliorated airway resistance and inflammation in this model of allergic asthma. Interestingly, the loss of CLR from the smooth muscle cells did not alter the airway resistance, indicating that CGRP does not act directly on the smooth muscle cells to drive airway hyperresponsiveness. Together, these data indicate that signaling through RAMP1 and CLR plays a role in mediating asthma pathology. Since RAMP1 and CLR interact to form a receptor for CGRP, our data indicate that aberrant CGRP signaling, perhaps on lung endothelial and inflammatory cells, contributes to asthma pathophysiology. Finally, since RAMP-receptor interfaces are pharmacologically tractable, it may be possible to develop compounds targeting the RAMP1/CLR

  12. In situ hybridization for the study of gene expression in neuro-otologic research.

    Science.gov (United States)

    Wackym, P A; Popper, P; Ward, P H; Micevych, P E

    1990-10-01

    In situ hybridization histochemistry technology was developed for future application to neuro-otologic research. This method allowed the detection of cellular mRNA in tissue sections from the temporal bone or brainstem after cRNA/mRNA hybridization. To produce specific cRNA, single-stranded 35S-labeled cRNA (complimentary to target mRNA) is transcribed from commercially available plasmid vectors. These vectors contain promotor sequences for specific synthesis of RNA, and polylinker regions that will accept cloned DNA inserts for virtually any target nucleic acid sequence of interest. The protocol used in this research was optimized for studies that included concomitant immunohistochemical evaluation. The combination of in situ hybridization and immunohistochemistry provides the only method to correlate molecular information (gene expression) with biochemical or molecular markers, such as peptides or proteins (mRNA translation products) on individual cells in the temporal bone or brainstem. Using these techniques, we examined the distribution of the neuropeptide calcitonin gene-related peptide in rat temporal bone and brainstem sections using calcitonin gene-related peptide (CGRP) antisera and CGRP cRNA probes. We used in situ hybridization histochemistry with a cRNA probe complementary to the 3'-end noncoding sequence of the alpha CGRP mRNA and immunohistochemistry with a polyclonal antibody to the (TYR)CGRP23-37 to study the distribution of CGRP mRNA and CGRP-like immunoreactivity in the central and peripheral facial nerve. Numerous motoneuron cell bodies in the facial nucleus and accessory seventh nucleus and cell bodies in the gustatory geniculate ganglion were found to contain CGRP mRNA and the CGRP peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1701043

  13. Combined use of 111In-DTPA-D-Phe-1-Octreotide (OCT) and 123I-Vasoactive Intestinal Peptide (VIP) in the localization diagnosis of medullary thyroid carcinoma (MTC)

    International Nuclear Information System (INIS)

    Although serum calcitonin and CEA are sensitive indicators for the presence of medullary thyroid carcinoma (MTC), the localization of tumor sites may be very difficult. In an approach to localize MTC lesions we performed comparative in vivo studies in 12 patients with primary MTC and in 4 patients with suspected recurrent MTC using 123I-VIP (150 MBq/1 μg) and 111In-DTPA-D-Phe-1-octreotide (111In-OCT; 150 MBq/1 μg). Despite elevated calcitonin values in all patients with suspected recurrent or metastatic lesions, both ultrasound and computed tomography (CT) were unable to localize a tumor site. 111In-OCT localized the primary tumor in the thyroid gland in 7 of 11 patients (63.5%). In 2 of 4 patients (50%) with suspected recurrent MTC, pathological uptake of 111In-OCT in the mediastinum or liver was demonstrable. In none of the 11 patients did 123I-VIP-receptor scanning indicate primary, recurrent, or metastatic tumor lesions. In vitro binding studies showed an absence of high-affinity VIP receptors in MTC tissue, whereas high-affinity 111In-OCT receptors were present in 4 of 6, and low-affinity 123I-VIP as well as 111In-OCT receptors were present in 6 of 6 MTC tissue samples. We conclude that somatostatin receptor scanning using 111In-OCT may visualize primary MTC, but it has only a low sensitivity in the detection of recurrent disease. The 123I-VIP-receptor scan is not helpful in the localization diagnosis of primary or recurrent MTC

  14. Contributors to Secondary Osteoporosis in Patients Referred for Treatment with Teriparatide

    Directory of Open Access Journals (Sweden)

    İnan Anaforoğlu

    2013-12-01

    Full Text Available Purpose: Teriparatide is an anabolic agent belonging to a new class of antiosteoporosis drugs. The Turkish Social Security Institution covers teriparatide for patients with osteoporosis who have 2 osteoporotic fractures, are older than 65 years, and have a T-score of less than -4. We evaluated possible secondary contributors to osteoporosis in patients referred for treatment with this agent. Material and Method: All patients referred to our center for teriparatide treatment over 2 year were evaluated for clinical risk factors for osteoporosis, medical history, and medications. Results: Sixty-eight patients (63 women and 5 men, mean age:71.3±9.4 (50-89 years were referred. Twenty-nine patients (42.6% had received osteoporosis therapy before referral, consisting of bisphosphonate (n=20, strontium ranelate (n=6, calcitonin (n=2, or calcitonin and bisphosphonate (n=1. The mean duration of the previous therapy was 46.4± 38.5 (3-120 months. In all, 50 of the 68 patients (73.5%, including all of the men, had a contributor to secondary osteoporosis. Vitamin D deficiency was the most frequent contributor in 34 patients (52.3%. Other common contributors were hyperthyroidism and hypogonadism. Only 3 of 18 patients with hyperthyroidism and none of the patients with hypogonadism had been diagnosed previously, and 16 of the 24 patients receiving vitamin D supplementation still had deficiency of this vitamin. Discussion: Most of our patients had a contributor to secondary osteoporosis, which often had not been identified previously. Identifying and correcting such disorders might improve the treatment of osteoporosis and reduce the risk of subsequent fracture. Turk Jem 2013; 17: 98-101

  15. Synergistic antitumour activity of RAF265 and ZSTK474 on human TT medullary thyroid cancer cells

    Science.gov (United States)

    Bertazza, Loris; Barollo, Susi; Radu, Claudia Maria; Cavedon, Elisabetta; Simioni, Paolo; Faggian, Diego; Plebani, Mario; Pelizzo, Maria Rosa; Rubin, Beatrice; Boscaro, Marco; Pezzani, Raffaele; Mian, Caterina

    2015-01-01

    Medullary thyroid cancer (MTC) is an aggressive malignancy responsible for up to 14% of all thyroid cancer-related deaths. It is characterized by point mutations in the rearranged during transfection (RET) proto-oncogene. The activated RET kinase is known to signal via extracellular signal regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K), leading to enhanced proliferation and resistance to apoptosis. In the present work, we have investigated the effect of two serine/threonine-protein kinase B-Raf (BRAF) inhibitors (RAF265 and SB590885), and a PI3K inhibitor (ZSTK474), on RET-mediated signalling and proliferation in a MTC cell line (TT cells) harbouring the RETC634W activating mutation. The effects of the inhibitors on VEGFR2, PI3K/Akt and mitogen-activated protein kinases signalling pathways, cell cycle, apoptosis and calcitonin production were also investigated. Only the RAF265+ ZSTK474 combination synergistically reduced the viability of treated cells. We observed a strong decrease in phosphorylated VEGFR2 for RAF265+ ZSTK474 and a signal reduction in activated Akt for ZSTK474. The activated ERK signal also decreased after RAF265 and RAF265+ ZSTK474 treatments. Alone and in combination with ZSTK474, RAF265 induced a sustained increase in necrosis. Only RAF265, alone and combined with ZSTK474, prompted a significant drop in calcitonin production. Combination therapy using RAF265 and ZSTK47 proved effective in MTC, demonstrating a cytotoxic effect. As the two inhibitors have been successfully tested individually in clinical trials on other human cancers, our preclinical data support the feasibility of their combined use in aggressive MTC. PMID:26081844

  16. Transient expression of somatostatin messenger RNA and peptide in the hypoglossal nucleus of the neonatal rat.

    Science.gov (United States)

    Seroogy, K B; Bayliss, D A; Szymeczek, C L; Hökfelt, T; Millhorn, D E

    1991-06-21

    The postnatal developmental expression of somatostatin mRNA and peptide in the rat hypoglossal nucleus was analyzed using immunocytochemical and in situ hybridization techniques. Both the neuropeptide and its cognate mRNA were found to be transiently present within a subpopulation of hypoglossal motoneurons during the neonatal period. At the day of birth, a large population of perikarya situated in caudal, ventral regions of the hypoglossal nucleus expressed somatostatin. By postnatal day 7, the number of hypoglossal somata which expressed somatostatin had diminished considerably, and by 2 weeks postnatal, only few such cell bodies were found. By 3-4 weeks postnatal, somatostatin peptide- and mRNA-containing hypoglossal motoneurons were rarely observed, and in the adult, they were never detected, despite the use of colchicine. A double-labeling co-localization technique was used to demonstrate that somatostatin, when present perinatally, always coexisted with calcitonin gene-related peptide in hypoglossal motoneurons. The latter peptide, in contrast to somatostatin, was expressed in large numbers of somata throughout the entire hypoglossal nucleus and persisted within the motoneurons throughout development into adulthood. These results demonstrate that somatostatin is transiently expressed in motoneurons of the caudal, ventral tier of the hypoglossal nucleus in the neonatal rat. The developmental disappearance of somatostatin is most likely not due to cell death; hypoglossal somata continue to express calcitonin gene-related peptide, with which somatostatin coexisted perinatally, a high levels throughout development. Thus, it appears that the regulation of somatostatin expression in hypoglossal neurons occurs at the level of gene transcription or mRNA stability/degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1680035

  17. A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium

    Directory of Open Access Journals (Sweden)

    Sparrow Malcolm P

    2005-10-01

    Full Text Available Abstract Background Pulmonary neuroendocrine cells (PNEC are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Methods Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1 undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5, sensory nerves (calcitonin gene related peptide, CGRP, and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP. The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. Results PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Conclusion Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.

  18. Incorporation of RANKL promotes osteoclast formation and osteoclast activity on β-TCP ceramics.

    Science.gov (United States)

    Choy, John; Albers, Christoph E; Siebenrock, Klaus A; Dolder, Silvia; Hofstetter, Wilhelm; Klenke, Frank M

    2014-12-01

    β-Tricalcium phosphate (β-TCP) ceramics are approved for the repair of osseous defects. In large defects, however, the substitution of the material by authentic bone is inadequate to provide sufficient long-term mechanical stability. We aimed to develop composites of β-TCP ceramics and receptor activator of nuclear factor κ-B ligand (RANKL) to enhance the formation of osteoclasts and promote cell mediated calcium phosphate resorption. RANKL was adsorbed superficially onto β-TCP ceramics or incorporated into a crystalline layer of calcium phosphate by the use of a co-precipitation technique. Murine osteoclast precursors were seeded onto the ceramics. After 15 days, the formation of osteoclasts was quantified cytologically and colorimetrically with tartrate-resistant acidic phosphatase (TRAP) staining and TRAP activity measurements, respectively. Additionally, the expression of transcripts encoding the osteoclast gene products cathepsin K, calcitonin receptor, and of the sodium/hydrogen exchanger NHA2 were quantified by real-time PCR. The activity of newly formed osteoclasts was evaluated by means of a calcium phosphate resorption assay. Superficially adsorbed RANKL did not induce the formation of osteoclasts on β-TCP ceramics. When co-precipitated onto β-TCP ceramics RANKL supported the formation of mature osteoclasts. The development of osteoclast lineage cells was further confirmed by the increased expression of cathepsin K, calcitonin receptor, and NHA2. Incorporated RANKL stimulated the cells to resorb crystalline calcium phosphate. Our in vitro study shows that RANKL incorporated into β-TCP ceramics induces the formation of active, resorbing osteoclasts on the material surface. Once formed, osteoclasts mediate the release of RANKL thereby perpetuating their differentiation and activation. In vivo, the stimulation of osteoclast-mediated resorption may contribute to a coordinated sequence of material resorption and bone formation. Further in vivo studies

  19. Localization of CGRP receptor components and receptor binding sites in rhesus monkey brainstem: A detailed study using in situ hybridization, immunofluorescence, and autoradiography.

    Science.gov (United States)

    Eftekhari, Sajedeh; Gaspar, Renee C; Roberts, Rhonda; Chen, Tsing-Bau; Zeng, Zhizhen; Villarreal, Stephanie; Edvinsson, Lars; Salvatore, Christopher A

    2016-01-01

    Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system and transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP, it is critical to identify the regions within the brainstem that process CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3)H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe nucleus, gracile nucleus, spinal trigeminal nucleus, and spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, trochlear nucleus, dorsal raphe nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens nucleus, and motor trigeminal nucleus; protein coexpression of CLR and RAMP1 was observed in these areas via immunofluorescence. [(3)H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that drugs inhibiting CGRP signaling may not be able to penetrate the central nervous system to antagonize receptors in these brain regions. PMID:26105175

  20. Comparison of 18F-DOPA, 18F-FDG and 68Ga-somatostatin analogue PET/CT in patients with recurrent medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    To retrospectively evaluate and compare 18F-FDG, 18F-DOPA and 68Ga-somatostatin analogues for PET/CT in patients with residual/recurrent medullary thyroid carcinoma (MTC) suspected on the basis of elevated serum calcitonin levels. Included in the study were 18 patients with recurrent MTC in whom functional imaging with the three tracers was performed. The PET/CT results were compared on a per-patient basis and on a per-lesion-basis. At least one focus of abnormal uptake was observed on PET/CT in 13 patients with 18F-DOPA (72.2% sensitivity), in 6 patients with 68Ga-somatostatin analogues (33.3%) and in 3 patients with 18F-FDG (16.7%) (p 18F-DOPA and 18F-FDG PET/CT (p 18F-DOPA and 68Ga-somatostatin analogue PET/CT (p = 0.04). Overall, 72 lesions were identified on PET/CT with the three tracers. 18F-DOPA PET/CT detected 85% of lesions (61 of 72), 68Ga-somatostatin analogue PET/CT 20% (14 of 72) and 18F-FDG PET/CT 28% (20 of 72). There was a statistically significant difference in the number of lymph node, liver and bone lesions detected with the three tracers (p 18F-DOPA PET/CT and 18F-FDG PET/CT (p 18F-DOPA PET/CT and 68Ga-somatostatin analogue PET/CT (p 18F-DOPA PET/CT seems to be the most useful imaging method for detecting recurrent MTC lesions in patients with elevated serum calcitonin levels, performing better than 18F-FDG and 68Ga-somatostatin analogue PET/CT. 18F-FDG may complement 18F-DOPA in patients with an aggressive tumour. (orig.)