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Sample records for vascular calcitonin gene-related

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  2. Colonic vascular conductance increased by Daikenchuto via calcitonin gene-related peptide and receptor-activity modifying protein 1.

    Science.gov (United States)

    Kono, Toru; Koseki, Takashi; Chiba, Shinichi; Ebisawa, Yoshiaki; Chisato, Naoyuki; Iwamoto, Jun; Kasai, Shinichi

    2008-11-01

    Daikencyuto (DKT) is a traditional Japanese medicine (Kampo) and is a mixture of extract powders from dried Japanese pepper, processed ginger, ginseng radix, and maltose powder and has been used as the treatment of paralytic ileus. DKT may increase gastrointestinal motility by an up-regulation of the calcitonin gene-related peptide (CGRP). CGRP is also the most powerful vasoactive substance. In the present study, we investigated whether DKT has any effect on the colonic blood flow in rats. Experiments were performed on fasted anesthetized and artificially ventilated Wistar rats. Systemic mean arterial blood pressure and heart rate were recorded. Red blood cell flux in colonic blood flow was measured using noncontact laser tissue blood flowmetry, and colonic vascular conductance (CVC) was calculated as the ratio of flux to mean arterial blood pressure. We examined four key physiological mechanisms underlying the response using blocker drugs: CGRP1 receptor blocker (CGRP(8-37)), nitric oxide synthase inhibitor, vasoactive intestinal polypeptide (VIP) receptor blocker ([4-Cl-DPhe6, Leu17]-VIP), and substance P receptor blocker (spantide). Reverse transcription-polymerase chain reaction was used for the detection of mRNA of calcitonin receptor-like receptor, receptor-activity modifying protein 1, the component of CGRP 1 receptor and CGRP. After laparotomy, a cannula was inserted into the proximal colon to administer the DKT and to measure CVC at the distal colon. Intracolonal administration of DKT (10, 100, and 300 mg/kg) increased CVC (basal CVC, 0.10 mL/mmHg) from the first 15-min observation period (0.14, 0.17, and 0.17 mL/mmHg, respectively) and with peak response at either 45 min (0.17 mL/mmHg by 10 mg/kg), or 75 and 60 min (0.23 and 0.21 mL/mmHg by 100 and 300 mg/kg, respectively). CGRP(8-37) completely abolished the DKT-induced hyperemia, whereas nitric oxide synthase inhibitor partially attenuated the DKT-induced hyperemia. [4-Cl-DPhe6, Leu17]-VIP and spantide

  3. Effects of salmon calcitonin and calcitonin gene related peptide ...

    African Journals Online (AJOL)

    The aim of this investigation was to examine and compare the effects of calcitonin gene related peptide (CGRP) and salmon calcitonin (sCT) on gastric lesions and mucosal barrier components such as mucus and phospholipids in rats exposed to cold + restraint stress (CRS). Twenty-eight Wistar albino rats (150 – 200 g) ...

  4. Calcitonin gene-related peptide and calcitonin in man

    International Nuclear Information System (INIS)

    Fischer, J.A.; Henke, H.; Petermann, J.B.; Tschopp, F.A.

    1985-01-01

    Calcitonin gene-related peptide has been identified in the human brain, spinal cord, pituitary and thyroid glands as assessed by RIA and RRA. An immunoreactive and receptoractive peak coeluting with synthetic hCGRP on gel permeation chromatography and HPLC has been recognized. The levels measured by RRA are generally higher than those by RIA. Different characteristics of hCGRP and sCT binding sites and the distinct regional distribution evaluated with membranes and receptor autoradiography indicate separate receptors of the two peptides. Our results suggest different physiological roles of CGRP and CT in the central nervous system which remain to be discovered. (Auth.)

  5. Calcitonin gene-related peptide and pain

    DEFF Research Database (Denmark)

    Schou, Wendy Sophie; Ashina, Sait; Amin, Faisal Mohammad

    2017-01-01

    and cerebrospinal fluid in subjects with musculoskeletal pain. A randomized clinical trial on monoclonal antibody, which selectively binds to and inhibits the activity of CGRP (galcanezumab) in patients with osteoarthritis knee pain, failed to demonstrate improvement of pain compared with placebo. No studies......BACKGROUND: Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP is involved in migraine pathophysiology but its role in non-headache pain has not been...... clarified. METHODS: We performed a systematic literature search on PubMed, Embase and ClinicalTrials.gov for articles on CGRP and non-headache pain covering human studies including experimental studies and randomized clinical trials. RESULTS: The literature search identified 375 citations of which 50...

  6. Serotonin, calcitonin and calcitonin gene-related peptide in acute pancreatitis

    DEFF Research Database (Denmark)

    Wahlstrøm, Kirsten Lykke; Novovic, Srdan; Ersbøll, Annette Kjær

    2017-01-01

    OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients with alco......OBJECTIVE: The aim of this study was to investigate plasma levels of serotonin, calcitonin and calcitonin gene-related peptide (CGRP) in the course of acute pancreatitis (AP) taking organ failure, etiology and severity into consideration. MATERIAL AND METHODS: Sixty consecutive patients...... dysfunction. We hypothesize that serotonin plays a pathogenic role in the compromised pancreatic microcirculation, and calcitonin a role as a biomarker of severity in AP....

  7. Calcitonin gene-related peptide antagonism and cluster headache

    DEFF Research Database (Denmark)

    Ashina, Håkan; Newman, Lawrence; Ashina, Sait

    2017-01-01

    Calcitonin gene-related peptide (CGRP) is a key signaling molecule involved in migraine pathophysiology. Efficacy of CGRP monoclonal antibodies and antagonists in migraine treatment has fueled an increasing interest in the prospect of treating cluster headache (CH) with CGRP antagonism. The exact...... role of CGRP and its mechanism of action in CH have not been fully clarified. A search for original studies and randomized controlled trials (RCTs) published in English was performed in PubMed and in ClinicalTrials.gov . The search term used was "cluster headache and calcitonin gene related peptide......" and "primary headaches and calcitonin gene related peptide." Reference lists of identified articles were also searched for additional relevant papers. Human experimental studies have reported elevated plasma CGRP levels during both spontaneous and glyceryl trinitrate-induced cluster attacks. CGRP may play...

  8. Calcitonin-gene related peptide and cerebral vasospasm.

    Science.gov (United States)

    Schebesch, Karl-Michael; Herbst, Andreas; Bele, Sylvia; Schödel, Petra; Brawanski, Alexander; Stoerr, Eva-Maria; Lohmeier, Annette; Kagerbauer, Simone Maria; Martin, Jan; Proescholdt, Martin

    2013-04-01

    The pathophysiology of arterial vasospasm following subarachnoid hemorrhage (SAH) is poorly understood and the contribution of endogenous neuropeptides has not been sufficiently elucidated. Recently, we detected an excessive release of vasoconstrictive neuropeptide Y (NPY) in SAH patients and identified a significant correlation of NPY cerebrospinal fluid (CSF) levels with vasospasm-related ischemia. Here, we present the results of an experimental study on the possible role of the potent endogenous vasodilator calcitonin-gene related peptide (CGRP) in the acute stage of SAH. Twelve consecutive patients with SAH were included. Seven patients had severe arterial vasospasm, confirmed by transcranial doppler-sonography (TCD). Prospectively, CSF was collected from day 1 to day 10 after onset of the SAH. The levels of CGRP were determined in a competitive enzyme immunoassay and were correlated with the clinical course and hemodynamic changes. A cohort of 29 patients without CNS disease served as a control. CGRP was significantly higher in SAH patients compared with the control group (p<0.05). From day 1 to day 4, the CGRP levels in patients without vasospasm were significantly higher than the levels of CGRP in patients with vasospasm (p<0.05). These patients did not develop cerebral ischemia. The significantly increased levels of the CGRP during the first days after onset of the SAH in the non-vasospasm group indicate a potential protective role of CGRP. CGRP may alleviate arterial vasoconstriction and thus protect the brain from vasospasm and subsequent ischemia. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors.

    Science.gov (United States)

    Poyner, David R; Sexton, Patrick M; Marshall, Ian; Smith, David M; Quirion, Remi; Born, Walter; Muff, Roman; Fischer, Jan A; Foord, Steven M

    2002-06-01

    The calcitonin family of peptides comprises calcitonin, amylin, two calcitonin gene-related peptides (CGRPs), and adrenomedullin. The first calcitonin receptor was cloned in 1991. Its pharmacology is complicated by the existence of several splice variants. The receptors for the other members the family are made up of subunits. The calcitonin-like receptor (CL receptor) requires a single transmembrane domain protein, termed receptor activity modifying protein, RAMP1, to function as a CGRP receptor. RAMP2 and -3 enable the same CL receptor to behave as an adrenomedullin receptor. Although the calcitonin receptor does not require RAMP to bind and respond to calcitonin, it can associate with the RAMPs, resulting in a series of receptors that typically have high affinity for amylin and varied affinity for CGRP. This review aims to reconcile what is observed when the receptors are reconstituted in vitro with the properties they show in native cells and tissues. Experimental conditions must be rigorously controlled because different degrees of protein expression may markedly modify pharmacology in such a complex situation. Recommendations, which follow International Union of Pharmacology guidelines, are made for the nomenclature of these multimeric receptors.

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

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  12. Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin.

    Science.gov (United States)

    Schlereth, Tanja; Schukraft, Jonas; Krämer-Best, Heidrun H; Geber, Christian; Ackermann, Tatiana; Birklein, Frank

    2016-10-01

    Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction. Different concentrations of SP (ranging from 10 -5 M to 10 -9 M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10 -9 M and CGRP 10 -6 M. As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10 -9 M and inhibited with co-application of CGRP10 -6 M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10 -6 M was added, the PPE significantly increased. Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10 -6 M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    Objective: The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine w...... without aura. This indicates that the pathophysiologic pathways underlying migraine headache in FHM may be different from the common types of migraine and questions whether CGRP antagonists would be effective in the treatment of FHM patients Udgivelsesdato: 2008/9/9...

  14. 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.

  15. Peripartal alterations of calcitonin gene-related peptide and minerals in dairy cows affected by milk fever.

    Science.gov (United States)

    Zebeli, Qendrim; Beitz, Donald C; Bradford, Barry J; Dunn, Suzanna M; Ametaj, Burim N

    2013-03-01

    Milk fever, a metabolic disease of dairy cattle, is associated with perturbations of calcium homeostasis, the pathogenesis of which is not yet completely understood. The aim of this study was to investigate plasma concentrations of calcitonin gene-related peptide and selected minerals and metabolites in periparturient cows with and without milk fever. Plasma concentrations of calcitonin gene-related peptide, as well as calcium, phosphate, magnesium, iron, glucose, lactate, and cortisol, were determined in multiple plasma samples from Jersey cows with and without spontaneous milk fever. Cows affected by milk fever (n = 5) had lower concentrations of calcitonin gene-related peptide (P = .038) and inorganic phosphate (P cows tended to have lower calcium concentrations (P = .071). Magnesium, iron, lactate, glucose, and cortisol concentrations were comparable between both groups of cows (P > .10). Around the day of calving, plasma concentrations of lactate, glucose, and cortisol increased and the concentration of iron decreased in all cows (P ≤ .01). Despite the limited number of cows evaluated, this report is the first to indicate lowered concentrations of calcitonin gene-related peptide as part of the metabolic changes during milk fever in cows. Further work with a larger cohort of animals is warranted to understand the precise role of calcitonin gene-related peptide and the potential associations with disturbances in plasma minerals typically observed during milk fever. © 2013 American Society for Veterinary Clinical Pathology.

  16. Calcitonin gene related family peptides: importance in normal placental and fetal development.

    Science.gov (United States)

    Yallampalli, Chandra; Chauhan, Madhu; Endsley, Janice; Sathishkumar, Kunju

    2014-01-01

    Synchronized molecular and cellular events occur between the uterus and the implanting embryo to facilitate successful pregnancy outcome. Nevertheless, the molecular signaling network that coordinates strategies for successful decidualization, placentation and fetal growth are not well understood. The discovery of calcitonin/calcitonin gene-related peptides (CT/CGRP) highlighted new signaling mediators in various physiological processes, including reproduction. It is known that CGRP family peptides including CGRP, adrenomedulin and intermedin play regulatory functions during implantation, trophoblast proliferation and invasion, and fetal organogenesis. In addition, all the CGRP family peptides and their receptor components are found to be expressed in decidual, placental and fetal tissues. Additionally, plasma levels of peptides of the CGRP family were found to fluctuate during normal gestation and to induce placental cellular differentiation, proliferation, and critical hormone signaling. Moreover, aberrant signaling of these CGRP family peptides during gestation has been associated with pregnancy disorders. It indicates the existence of a possible regulatory role for these molecules during decidualization and placentation processes, which are known to be particularly vulnerable. In this review, the influence of the CGRP family peptides in these critical processes is explored and discussed.

  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

    The distribution of nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) was investigated by immunohistochemistry in nipples and mammary glands from lactating and non-lactating rats and compared to the immunoreactivity of other neuropeptides including substance P (SP), neuropepti...... in the nipples of the pregnant (day 10) rats exceeded almost ninefold the maximum concentration of SP (7.7 +/- 2.0 pmol/g).(ABSTRACT TRUNCATED AT 250 WORDS)....... 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. Effect of prepro-calcitonin gene-related peptide-expressing endothelial progenitor cells on pulmonary hypertension.

    Science.gov (United States)

    Zhao, Qiang; Liu, Zixiong; Wang, Zhe; Yang, Cheng; Liu, Jun; Lu, Jun

    2007-08-01

    Calcitonin gene-related peptide (CGRP) is a potent smooth muscle cell proliferation inhibitor and vasodilator. It is now believed that CGRP plays an important role in maintaining a low pulmonary vascular resistance. We evaluated the therapeutic effect of intravenously administered CGRP-expressing endothelial progenitor cells (EPCs) on left-to-right shunt-induced pulmonary hypertension in rats. Endothelial progenitor cells were obtained from cultured human peripheral blood mononuclear cells. The genetic sequence for CGRP was subcloned into cultured EPCs by human expression plasmid. Pulmonary hypertension was established in immunodeficient rats with an abdominal aorta to inferior vena cava shunt operation. The transfected EPCs were injected through the left jugular vein at 10 weeks after the shunt operation. Mean pulmonary artery pressure and total pulmonary vascular resistance were detected with right cardiac catheterization at 4 weeks. The distribution of EPCs in the lung tissue was examined with immunofluorescence technique. Histopathologic changes in the structure of the pulmonary arteries was observed with electron microscopy and subjected to computerized image analysis. The lungs of rats transplanted with CGRP-expressing EPCs demonstrated a decrease in both mean pulmonary artery pressure (17.64 +/- 0.79 versus 22.08 +/- 0.95 mm Hg; p = 0.018) and total pulmonary vascular resistance (1.26 +/- 0.07 versus 2.45 +/- 0.18 mm Hg x min/mL; p = 0.037) at 4 weeks. Immunofluorescence revealed that intravenously administered cells were incorporated into the pulmonary vasculature. Pulmonary vascular remodeling was remarkably attenuated with the administration of CGRP-expressing EPCs. The transplantation of CGRP-expressing EPCs may effectively attenuate established pulmonary hypertension and exert reversal effects on pulmonary vascular remodeling. Our findings suggest that the therapy based on the combination of both CGRP transfection and EPCs may be a potentially useful

  19. 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

    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...

  20. Carotid blood flow distribution, haemodynamics and inotropic responses following calcitonin gene-related peptide in the pig

    NARCIS (Netherlands)

    E.M. van Gelderen (E.); X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractThe sensory neuropeptide, calcitonin gene-related peptide (α-CGRP), has been implicated in the pathogenesis of migraine headache. The present study aimed to evaluate the effects of intracarotid infusions of human α-CGRP (10, 30 and 100 pmol/kg · min; n = 8), as compared to that of saline

  1. Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

    Science.gov (United States)

    Gangula, P R; Wimalawansa, S J; Yallampalli, C

    1997-04-01

    We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

  2. Bio-Oss® modified by calcitonin gene-related peptide promotes osteogenesis in vitro.

    Science.gov (United States)

    Li, Yuanjing; Yang, Lan; Zheng, Zhichao; Li, Zhengmao; Deng, Tian; Ren, Wen; Wu, Caijuan; Guo, Lvhua

    2017-11-01

    Bio-Oss ® and α-calcitonin gene-related peptide (CGRP) are involved in osteogenesis. However, it has remained to be assessed how α-CGRP affects the effect of Bio-Oss. In the present study, primary osteoblasts were incubated with α-CGRP, Bio-Oss, α-GGRP-Bio-Oss or mimic-α-CGRP. The proliferation rate, mineralization nodules, alkaline phosphatase (ALP) activity and the expression of osteogenic genes were measured by a Cell Counting Kit-8 assay, Alizarin Red-S staining, ALP activity detection and reverse-transcription quantitative PCR as well as western blot analysis, respectively. The proliferation rate, ALP activity and the number of mineralization nodules were significantly increased in the α-CGRP-modified Bio-Oss group compared to that in the Bio-Oss group. The mRNA and protein levels of osteocalcin, Runt-related transcription factor-2 and ALP were significantly upregulated in the α-CGRP-Bio-Oss group compared with those in the Bio-Oss group. Furthermore, the effect of mimic-α-CGRP on osteogenesis was reduced as it carried a mutation. In conclusion, the present study was the first to demonstrate that Bio-Oss modified with CGRP contributed to osteogenesis and may provide a novel formulation applied in the clinic for restoration of large bone defects.

  3. Analysis of plasma edothelin and calcitonin gene-related peptide in aged patients undergoing laparoscopic cholecystectomy

    International Nuclear Information System (INIS)

    Sun Wei; Zhu Gaohong; Wei Jiangliang; Hu Jianwei

    2011-01-01

    Objective: To investigate the effects of laparoscopic cholecystectomy on the plasma levels of endothelin and calcitonin gene-related peptide (CGRP)in elderly patients. Methods: Sixty patients undergoing elective laoaroscopic cholecystectomy were divided into 65 years old group according to their ages (30 cases in each group). The plasma levels of endothelin and CGRP were measured before surgery, after intubation, at the time of gallbladder removal, immediately after surgery and 24 hours after surgery by radioimmunoassay. Results: There was no significant difference in endothelin levels between the two groups before the surgery (t=0.971, P>0.05). The endothelin levels in both groups gradually increased after the intubation, but more significantly in the > 65 years old group (t=4.258, P 65 years old group (t=5.134, P 65 years old group continued to increase, but it decreased in the 0.05). The CGRP levels had not significantly changed during the perioperative period in the 65 years old group, CGRP levels decreased after anaesthesia, but increased during the surgery, and then reached the highest level at the time of the surgery completed. CGRP levels were significant difference between the two groups after intubation and immediately after surgery (t=4.084 and t=4.085, P<0.05). Conclusion: The levels of endothelin and CGRP had significantly changed elderly patients than those in young patients, especially for endothelin. (authors)

  4. Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract☆

    Science.gov (United States)

    Abbey, Marcie J.; Patil, Vinit V.; Vause, Carrie V.; Durham, Paul L.

    2008-01-01

    Ethnopharmacological relevance Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. Aim of the study To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. Results Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24 h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. Conclusions Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation. PMID:17997062

  5. Repression of calcitonin gene-related peptide expression in trigeminal neurons by a Theobroma cacao extract.

    Science.gov (United States)

    Abbey, Marcie J; Patil, Vinit V; Vause, Carrie V; Durham, Paul L

    2008-01-17

    Cocoa bean preparations were first used by the ancient Maya and Aztec civilizations of South America to treat a variety of medical ailments involving the cardiovascular, gastrointestinal, and nervous systems. Diets rich in foods containing abundant polyphenols, as found in cocoa, underlie the protective effects reported in chronic inflammatory diseases. Release of calcitonin gene-related peptide (CGRP) from trigeminal nerves promotes inflammation in peripheral tissues and nociception. To determine whether a methanol extract of Theobroma cacao L. (Sterculiaceae) beans enriched for polyphenols could inhibit CGRP expression, both an in vitro and an in vivo approach was taken. Treatment of rat trigeminal ganglia cultures with depolarizing stimuli caused a significant increase in CGRP release that was repressed by pretreatment with Theobroma cacao extract. Pretreatment with Theobroma cacao was also shown to block the KCl- and capsaicin-stimulated increases in intracellular calcium. Next, the effects of Theobroma cacao on CGRP levels were determined using an in vivo model of temporomandibular joint (TMJ) inflammation. Capsaicin injection into the TMJ capsule caused an ipsilateral decrease in CGRP levels. Theobroma cacao extract injected into the TMJ capsule 24h prior to capsaicin treatment repressed the stimulatory effects of capsaicin. Our results demonstrate that Theobroma cacao extract can repress stimulated CGRP release by a mechanism that likely involves blockage of calcium channel activity. Furthermore, our findings suggest that the beneficial effects of diets rich in cocoa may include suppression of sensory trigeminal nerve activation.

  6. 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.

  7. Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide.

    Science.gov (United States)

    Szklany, Kirsten; Ruiter, Evelyn; Mian, Firoz; Kunze, Wolfgang; Bienenstock, John; Forsythe, Paul; Karimi, Khalil

    2016-01-01

    The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body's internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4+ T cell: neuron interaction through the release of neuropeptide CGRP.

  8. Pharmacologic study of C-terminal fragments of frog skin calcitonin gene-related peptide.

    Science.gov (United States)

    Ladram, Ali; Besné, Isabelle; Breton, Lionel; de Lacharrière, Olivier; Nicolas, Pierre; Amiche, Mohamed

    2008-07-01

    The calcitonin gene-related peptide from the skin of the frog Phyllomedusa bicolor (pbCGRP) is a 37-residue neuropeptide that differs from human alpha CGRP (halphaCGRP) at 16 positions. The affinities of the C-terminal fragments of pbCGRP and halphaCGRP were evaluated in SK-N-MC cells: pbCGRP(8-37) (K(i)=0.2nM) and pbCGRP(27-37) (K(i)=95nM) were, respectively, 3 times and 20 times more potent than the human fragments halphaCGRP(8-37) and halphaCGRP(27-37). Their antagonistic potencies were measured in SK-N-MC and Col 29 cells, and the rat vas deferens. pbCGRP(8-37) inhibited the halphaCGRP-stimulated production of cAMP by SK-N-MC and Col 29 cells 3 to 4 times more strongly than halphaCGRP(8-37). Thus pbCGRP(8-37) is the most potent CGRP-1 competitive antagonist of all the natural sequences reported to date. pbCGRP(27-37) was also as potent as [D(31), A(34), F(35)] halphaCGRP(27-37), a prototypic antagonist analog derived from structure-activity relationship studies of halphaCGRP(8-37).

  9. Acupuncture as Treatment of Hot Flashes and the Possible Role of Calcitonin Gene-Related Peptide

    Directory of Open Access Journals (Sweden)

    Anna-Clara E. Spetz Holm

    2012-01-01

    Full Text Available The mechanisms behind hot flashes in menopausal women are not fully understood. The flashes in women are probably preceded by and actually initiated by a sudden downward shift in the set point for the core body temperature in the thermoregulatory center that is affected by sex steroids, β-endorphins, and other central neurotransmitters. Treatments that influence these factors may be expected to reduce hot flashes. Since therapy with sex steroids for hot flashes has appeared to cause a number of side effects and risks and women with hot flashes and breast cancer as well as men with prostate cancer and hot flashes are prevented from sex steroid therapy there is a great need for alternative therapies. Acupuncture affecting the opioid system has been suggested as an alternative treatment option for hot flashes in menopausal women and castrated men. The heat loss during hot flashes may be mediated by the potent vasodilator and sweat gland activator calcitonin gene-related peptide (CGRP the concentration of which increases in plasma during flashes in menopausal women and, according to one study, in castrated men with flushes. There is also evidence for connections between the opioid system and the release of CGRP. In this paper we discuss acupuncture as a treatment alternative for hot flashes and the role of CGRP in this context.

  10. 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.

  11. Calcitonin gene-related peptide modulates heat nociception in the human brain - An fMRI study in healthy volunteers

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  12. [Clinical significance of calcitonin gene-related peptide level before and after treatment in patients with chronic periodontitis].

    Science.gov (United States)

    Yan, Ying; Xiang, Xue-Rong; Wang, Chun; Ye, Guo; Fan, Xiao-Ping

    2016-08-01

    To explore the clinical significance of calcitonin gene-related peptide (CGRP) levels in patients with chronic periodontitis before and after treatment, and to detect the calcitonin gene-related peptide content in human venous blood. Thirty healthy controls and thirty patients with mild, moderate, severe periodontitis were enrolled from August 2014 to June 2015.CGRP level in the patients' peripheral blood was detected by ELISA. Three months after periodontal treatment, CGRP level in mild, moderate, severe periodontitis patients' peripheral blood was re-examined by ELISA. Then the correlation between calcitonin gene-related peptide and inflammation of chronic periodontitis was analyzed with SPSS 22.0 software package. The content of CGRP in healthy controls was significantly higher than that in patients with periodontitis. With the aggravation of periodontal inflammation, blood level of CGRP decreased gradually, and the lowest was in patients with severe periodontitis (Pperiodontal treatment, CGRP content was significantly higher compared with that before treatment (Pperiodontitis (P>0.05). The level of CGRP in venous blood decreased with the increasing severity of chronic periodontitis, and CGRP was negatively correlated with the degree of inflammation of chronic periodontitis. CGRP may be involved in the occurrence and development of chronic periodontitis. CGRP content in serum of patients with chronic periodontitis after treatment was significantly increased, CGRP may be used as the basis for clinical detection of chronic periodontitis.

  13. The diagnosis value of endothelin, calcitonin gene-related peptide and the ratio in diabetic nephropathy

    International Nuclear Information System (INIS)

    Li Lusheng; Zhao Xin; Chi Liuying; Yang Xixiu; Mao Hongyu

    2007-01-01

    Objective: To evaluate the diagnosis value of Endothelin (ET), Calcitonin gene-related peptide(CGRP) and theratio in diabetic nephropathy(DN). Methods: To choose 54 healthy as the control group and 124 patients with diabetes or DN as test group. According to urinary albumin excretion rate (uAER), the test group was divided into three groups, which were diabetes group of normalalbuminmia (group A), early DN (group B) and clinical DN and renal failure group( group C ). Plasma concentration of ET and CGRP were measured with radioimmunossay for those in the Control group and patients with diabetes or DN. Results: The level of ET was significantly higher in diabetic nephropathy than that in the control group (P<0.01), and there was positive correlation between ET and uAER(r=0.591, P<0.01). The plasma level of CGRP was significantly lower in diabetic nephropathy than that in the control group (P<0.01), and there was negative correlation between CGRP and uAER(r-0.389, P<0.05). The level of ET, CGRP and ET/CGRP ratio have evidently changed with the uAER rised. Conclusion: (1)The level of ET, CGRP and type 2 diabetic nephropathy are closely related, and which probably plays a role in the development of DN. (2)ET/CGRP ratio, as a new way for diagnosis, can even more reflecte the seriousness of DN. (3)This experiment provide us a new way for the prevention and treatment of DN with extrinsic CGRP. (authors)

  14. In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle.

    Science.gov (United States)

    Pohl, M; Collin, E; Bourgoin, S; Clot, A M; Hamon, M; Cesselin, F; Le Bars, D

    1992-10-01

    The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha-calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres.

  15. Isolation, structure, synthesis, and activity of a new member of the calcitonin gene-related peptide family from frog skin and molecular cloning of its precursor.

    Science.gov (United States)

    Seon, A A; Pierre, T N; Redeker, V; Lacombe, C; Delfour, A; Nicolas, P; Amiche, M

    2000-02-25

    Calcitonin gene-related peptide has been extracted from the skin exudate of a single living specimen of the frog Phyllomedusa bicolor and purified to homogeneity by a two-step protocol. A total volume of 250 microl of exudate yielded 380 microg of purified peptide. Mass spectrometric analysis and gas phase sequencing of the purified peptide as well as chemical synthesis and cDNA analysis were consistent with the structure SCDTSTCATQRLADFLSRSGGIGSPDFVPTDVSANSF amide and the presence of a disulfide bridge linking Cys(2) and Cys(7). The skin peptide, named skin calcitonin gene-related peptide, differs significantly from all other members of the calcitonin gene-related peptide family of peptides at nine positions but binds with high affinity to calcitonin gene-related peptide receptors in the rat brain and acts as an agonist in the rat vas deferens bioassay with potencies equal to those of human CGRP. Reverse transcriptase-polymerase chain reaction coupled with cDNA cloning and sequencing demonstrated that skin calcitonin gene-related peptide isolated in the skin is identical to that present in the frog's central and enteric nervous systems. These data, which indicate for the first time the existence of calcitonin gene-related peptide in the frog skin, add further support to the brain-skin-gut triangle hypothesis as a useful tool in the identification and/or isolation of mammalian peptides that are present in the brain and other tissues in only minute quantities.

  16. Calcitonin Gene-Related Peptide Induces HIV-1 Proteasomal Degradation in Mucosal Langerhans Cells.

    Science.gov (United States)

    Bomsel, Morgane; Ganor, Yonatan

    2017-12-01

    The neuroimmune dialogue between peripheral neurons and Langerhans cells (LCs) within mucosal epithelia protects against incoming pathogens. LCs rapidly internalize human immunodeficiency virus type 1 (HIV-1) upon its sexual transmission and then trans -infect CD4 + T cells. We recently found that the neuropeptide calcitonin gene-related peptide (CGRP), secreted mucosally from peripheral neurons, inhibits LC-mediated HIV-1 trans -infection. In this study, we investigated the mechanism of CGRP-induced inhibition, focusing on HIV-1 degradation in LCs and its interplay with trans -infection. We first show that HIV-1 degradation occurs in endolysosomes in untreated LCs, and functionally blocking such degradation with lysosomotropic agents results in increased trans -infection. We demonstrate that CGRP acts via its cognate receptor and at a viral postentry step to induce faster HIV-1 degradation, but without affecting the kinetics of endolysosomal degradation. We reveal that unexpectedly, CGRP shifts HIV-1 degradation from endolysosomes toward the proteasome, providing the first evidence for functional HIV-1 proteasomal degradation in LCs. Such efficient proteasomal degradation significantly inhibits the first phase of trans -infection, and proteasomal, but not endolysosomal, inhibitors abrogate CGRP-induced inhibition. Together, our results establish that CGRP controls the HIV-1 degradation mode in LCs. The presence of endogenous CGRP within innervated mucosal tissues, especially during the sexual response, to which CGRP contributes, suggests that HIV-1 proteasomal degradation predominates in vivo Hence, proteasomal, rather than endolysosomal, HIV-1 degradation in LCs should be enhanced clinically to effectively restrict HIV-1 trans -infection. IMPORTANCE During sexual transmission, HIV-1 is internalized and degraded in LCs, the resident antigen-presenting cells in mucosal epithelia. Yet during trans -infection, infectious virions escaping degradation are transferred

  17. Multiple affinity forms of the calcitonin gene-related peptide receptor in rat cerebellum

    International Nuclear Information System (INIS)

    Chatterjee, T.K.; Fisher, R.A.

    1991-01-01

    Binding of 125I-calcitonin gene-related peptide (125I-CGRP) to rat cerebellum membranes and the sensitivity to guanine nucleotides of binding were investigated. Cerebellum binding sites labeled by 125I-CGRP appear to be highly specific, inasmuch as CGRP inhibited binding with an IC50 of 100 pM but other peptides were inactive or much less active in displacing 125I-CGRP from these sites. 125I-CGRP binding sites in cerebellum membranes were saturable and of high affinity. Scatchard analysis of the saturation binding data revealed a homogeneous population of binding sites, with a KD of 224 ± 28 pM and Bmax of 131 ± 15 fmol/mg of protein. In the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) (100 microM), a single population of binding sites, with a KD of 464 ± 77 pM and Bmax of 100 ± 14 fmol/mg of protein, was observed. The kinetics of association of 125I-CGRP with cerebellum membranes were monophasic at all ligand concentrations tested. However, the observed association rate constant (kobs) was not dependent on [125I-CGRP] in a linear fashion in either the absence or the presence of GTP gamma S (100 microM). The kinetics of dissociation of 125I-CGRP from cerebellum membranes were multiexponential, with fast and slow dissociating components having rate constants of 0.34 ± 0.01 and 0.025 ± 0.001 min-1, respectively. The fast dissociating component represented 60 ± 2% of the total specific binding sites. Dissociation of 125I-CGRP from cerebellum sites was much faster in the presence of GTP gamma S (100 microM) but still exhibited dissociation from two affinity components. The rate constants for these components of dissociation were 0.67 ± 0.03 and 0.077 ± 0.007 min-1, with the faster dissociating component representing 66 ± 1% of the total specific binding sites

  18. Calcitonin Gene-Related Peptide Reduces Taste-Evoked ATP Secretion from Mouse Taste Buds.

    Science.gov (United States)

    Huang, Anthony Y; Wu, Sandy Y

    2015-09-16

    Immunoelectron microscopy revealed that peripheral afferent nerve fibers innervating taste buds contain calcitonin gene-related peptide (CGRP), which may be as an efferent transmitter released from peripheral axon terminals. In this report, we determined the targets of CGRP within taste buds and studied what effect CGRP exerts on taste bud function. We isolated mouse taste buds and taste cells, conducted functional imaging using Fura-2, and used cellular biosensors to monitor taste-evoked transmitter release. The findings showed that a subset of Presynaptic (Type III) taste cells (53%) responded to 0.1 μm CGRP with an increase in intracellular Ca(2+). In contrast, Receptor (Type II) taste cells rarely (4%) responded to 0.1 μm CGRP. Using pharmacological tools, the actions of CGRP were probed and elucidated by the CGRP receptor antagonist CGRP(8-37). We demonstrated that this effect of CGRP was dependent on phospholipase C activation and was prevented by the inhibitor U73122. Moreover, applying CGRP caused taste buds to secrete serotonin (5-HT), a Presynaptic (Type III) cell transmitter, but not ATP, a Receptor (Type II) cell transmitter. Further, our previous studies showed that 5-HT released from Presynaptic (Type III) cells provides negative paracrine feedback onto Receptor (Type II) cells by activating 5-HT1A receptors, and reducing ATP secretion. Our data showed that CGRP-evoked 5-HT release reduced taste-evoked ATP secretion. The findings are consistent with a role for CGRP as an inhibitory transmitter that shapes peripheral taste signals via serotonergic signaling during processing gustatory information in taste buds. The taste sensation is initiated with a highly complex set of interactions between a variety of cells located within the taste buds before signal propagation to the brain. Afferent signals from the oral cavity are carried to the brain in chemosensory fibers that contribute to chemesthesis, the general chemical sensitivity of the mucus

  19. Effects of endogenous nitric oxide on adrenergic nerve-mediated vasoconstriction and calcitonin gene-related peptide-containing nerve-mediated vasodilation in pithed rats.

    Science.gov (United States)

    Yamawaki, Kousuke; Zamami, Yoshito; Kawasaki, Hiromu; Takatori, Shingo

    2017-05-05

    Vascular adrenergic nerves mainly regulate the tone of blood vessels. Calcitonin gene-related peptide-containing (CGRPergic) vasodilator nerves also participate in the regulation of vascular tone. Furthermore, there are nitric oxide (NO)-containing (nitrergic) nerves, which include NO in blood vessels as vasodilator nerves, but it remains unclear whether nitrergic nerves participate in vascular regulation. The present study investigated the role of nitrergic nerves in vascular responses to spinal cord stimulation (SCS) and vasoactive agents in pithed rats. Wistar rats were anesthetized and pithed, and vasopressor responses to SCS and injections of norepinephrine were observed. To evaluate vasorelaxant responses, the BP was increased by a continuous infusion of methoxamine with hexamethonium to block autonomic outflow. After the elevated BP stabilized, SCS and injections of acetylcholine (ACh), sodium nitroprusside (SNP), and CGRP were intravenously administered. We then evaluated the effects of the NO synthase (NOS) inhibitor, N-ω-nitro-L-arginine methylester hydrochloride (L-NAME), on these vascular responses. Pressor responses to SCS and norepinephrine in pithed rats were enhanced by L-NAME, while the combined infusion of L-NAME and L-arginine had no effect on these responses. L-NAME infusion significantly increased the release of norepinephrine evoked by SCS. In pithed rats with artificially increased BP and L-NAME infusion, depressor response to ACh (except for 0.05nmol/kg) was suppressed and SNP (only 2nmol/kg) was enhanced. However, depressor responses to SCS and CGRP were similar to control responses. The present results suggest endogenous NO regulates vascular tone through endothelium function and inhibition of adrenergic neurotransmission, but not through CGRPergic nerves. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Calcitonin gene-related peptide promotes the wound healing of human bronchial epithelial cells via PKC and MAPK pathways.

    Science.gov (United States)

    Zhou, Yong; Zhang, Min; Sun, Guo-Ying; Liu, Yong-Ping; Ran, Wen-Zhuo; Peng, Li; Guan, Cha-Xiang

    2013-06-10

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide derived from the calcitonin gene. CGRP is widely distributed in the central and peripheral neuronal systems. In the lung, CGRP could modulate dendritic cell function, stimulate proliferation of alveolar epithelial cells and mediate lung injury in mice. In this study, we investigated the effect of CGRP on the wound healing of human bronchial epithelial cells (HBECs) in vitro. The results showed that CGRP accelerated the recovery of wound area of monolayer HBECs in a dose-dependent manner. CGRP inhibited the lipopolysaccharide-induced apoptosis in HBECs. The percentage of S phase and G2/M phase was increased in HBECs after CGRP treatment. CGRP upregulated the expression of Ki67 in a dose-dependent manner. Some pathway inhibitors were used to investigate the signal pathway in which CGRP was involved. We found out that PKC pathway inhibitor (H-7) and MAPK pathway inhibitor (PD98059) could partially attenuate the effect of CGRP, which indicated that CGRP might promote the wound healing of HBECs via PKC and/or MAPK dependent pathway by accelerating migration and proliferation, and inhibiting apoptosis. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. 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

    BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo-contro...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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 migrai...

  3. [The effect of calcitonin gene-related peptide on collagen accumulation in pulmonary arteries of rats with hypoxic pulmonary arterial hypertension].

    Science.gov (United States)

    Li, Xian-Wei; Du, Jie; Li, Yuan-Jian

    2013-03-01

    To observe the effect of calcitonin gene-related peptide (CGRP) on pulmonary vascular collagen accumulation in hypoxia rats in order to study the effect of CGRP on hypoxic pulmonary vascular structural remodeling and its possible mechanism. Rats were acclimated for 1 week, and then were randomly divided into three groups: normoxia group, hypoxia group, and hypoxia plus capsaicin group. Pulmonary arterial hypertension was induced by hypoxia in rats. Hypoxia plus capsaicin group, rats were given capsaicin (50 mg/(kg x d), s.c) 4 days before hypoxia to deplete endogenous CGRP. Hypoxia (3% O2) stimulated proliferation of pulmonary arterial smooth muscle cells (PASMCs) and proliferation was measured by BrdU marking. The expression levels of CGRP, phosphorylated ERK1/2 (p-ERK1/ 2), collagen I and collagen III were detected by real-time PCR or Western blot. Right ventricle systolic pressure (RVSP) and mean pulmonary arterial pressure (mPAP) of pulmonary arterial hypertension (PAH) rats induced by hypoxia were higher than those of normoxia rats. By HE and Masson staining, it was demonstrated that hypoxia also significantly induced hypertrophy of pulmonary arteries and increased level of collagen accumulation. Hypoxia dramatically decreased the CGRP level and increased the expression of p-ERK1/2, collagen I, collagen III in pulmonary arteries. All these effects of hypoxia were further aggravated by pre-treatment of rats with capsaicin. CGRP concentration-dependently inhibited hypoxia-induced proliferation of PASMCs, markedly decreased the expression of p-ERK1/2, collagen I and collagen III. All these effects of CGRP were abolished in the presence of CGRP8-37. These results suggest that CGRP might inhibit hypoxia-induced PAH and pulmonary vascular remodeling, through inhibiting phosphorylation of ERK1/2 and alleviating the collagen accumulation of pulmonary arteries.

  4. Effects of NSAIDs on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Trigeminal Ganglia

    Directory of Open Access Journals (Sweden)

    Vittorio Vellani

    2017-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to treat migraine, but the mechanisms of their effects in this pathology are not fully elucidated. The trigeminal ganglia and calcitonin gene-related peptide (CGRP have been implicated in the pathophysiology of migraine. The release of CGRP and prostaglandin E2 (PGE2 from freshly isolated rat trigeminal ganglia was evaluated after oral administration of nimesulide, etoricoxib, and ketoprofen, NSAIDs with different pharmacological features. Thirty minutes after oral administration, nimesulide, 10 mg/Kg, decreased the GCRP release induced by an inflammatory soup, while the other NSAIDs were ineffective at this point in time. Two hours after oral nimesulide (5 and 10 mg/Kg and ketoprofen (10 mg/Kg, but not of etoricoxib, a significant decrease in the CGRP release was observed. All drugs reduced PGE2, although with some differences in timing and doses, and the action on CGRP does not seem to be related to PGE2 inhibition. The reduction of CGRP release from rat trigeminal ganglia after nimesulide and ketoprofen may help to explain the mechanism of action of NSAIDs in migraine. Since at 30 minutes only nimesulide was effective in reducing CGRP release, these results suggest that this NSAID may exert a particularly rapid effect in patients with migraine.

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

    International Nuclear Information System (INIS)

    Mak, J.C.; Barnes, P.J.

    1988-01-01

    125 I-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 125 I-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

  6. Activation of calcitonin gene-related peptide receptor during ozone inhalation contributes to airway epithelial injury and repair.

    Science.gov (United States)

    Oslund, Karen L; Hyde, Dallas M; Putney, Leialoha F; Alfaro, Mario F; Walby, William F; Tyler, Nancy K; Schelegle, Edward S

    2009-10-01

    The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP(8-37)) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5'-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP(8-37) had significantly reduced epithelial injury in terminal bronchioles and reduced epithelial proliferation in proximal airways and terminal bronchioles. Bronchoalveolar lavage and sections of terminal bronchioles showed no significant difference in the number of neutrophils emigrating into airways in CGRP(8-37)-treated rats. The airway epithelial cell line, HBE-1, showed no difference in the number of oxidant stress positive cells during exposure to hydrogen peroxide and a range of CGRP(8-37) doses, demonstrating no antioxidant effect of CGRP(8-37). We conclude that activation of CGRP receptors during ozone inhalation contributes to airway epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

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

    Science.gov (United States)

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

    2005-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Cady Ryan J

    2011-12-01

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

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

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    Qin Yang

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

  10. Calcitonin gene-related peptide: neuroendocrine communication between the pancreas, gut, and brain in regulation of blood glucose.

    Science.gov (United States)

    Pendharkar, Sayali A; Walia, Monika; Drury, Marie; Petrov, Maxim S

    2017-11-01

    Calcitonin gene-related peptide (CGRP), a ubiquitous neuropeptide, plays a diverse and intricate role in chronic low-grade inflammation, including conditions such as obesity, type 2 diabetes, and diabetes of the exocrine pancreas. Diabetes of exocrine pancreas is characterised by chronic hyperglycemia and is associated with persistent low-grade inflammation and altered secretion of certain pancreatic and gut hormones. While CGRP may regulate glucose homeostasis and the secretion of pancreatic and gut hormones, its role in chronic hyperglycemia after acute pancreatitis (CHAP) is not known. The aim of this study was to investigate the association between CGRP and CHAP. Fasting blood samples were collected to measure insulin, HbA1c, CGRP, amylin, C-peptide, glucagon, pancreatic polypeptide (PP), somatostatin, gastric inhibitory peptide, glicentin, glucagon-like peptide-1 and 2, and oxyntomodulin. Modified Poisson regression analysis and linear regression analyses were conducted. Five statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 patients were recruited. CGRP was significantly associated with CHAP in all five models (P-trend <0.005). Further, it was significantly associated with oxyntomodulin (P<0.005) and glucagon (P<0.030). Oxyntomodulin and glucagon independently contributed 9.7% and 7%, respectively, to circulating CGRP variance. Other pancreatic and gut hormones were not significantly associated with CGRP. CGRP is involved in regulation of blood glucose in individuals after acute pancreatitis. This may have translational implications in prevention and treatment of diabetes of the exocrine pancreas.

  11. Radioimmunoassay for calcitonin gene-related peptide and its measurement in sera of patients with thyroid disease

    International Nuclear Information System (INIS)

    Yoshida, Hiromi; Morii, Hirotoshi; Hamada, Noboru; Noh, Jaeduk; Ito, Kunihiko.

    1992-01-01

    To investigate serum levels of calcitonin gene-related peptide (CGRP), we developed a sensitive radioimmunoassay (RIA). RIA for CGRP in serum can present problems: the serum may degradate the tracer during incubation and suppress the antigen-antibody reaction. We avoided these problems by using aprotinin and CGRP-free serum instead of a buffer for the standard curve. We detected serum CGRP in all 39 healthy subjects when CGRP-free serum was not used for the standard curve, but 34 of these subjects had serum CGRP levels below the detection limit (<80 pmol/l) when CGRP-free serum was used for the standard curve. We defined the normal range for serum CGRP as below 100.8 pmol/l, which was the maximum level found in the healthy subjects. We studied serum levels of this peptide in patients with thyroid disease, because the thyroid may be one origin of circulating CGRP. Four of 10 patients with medullary thyroid carcinoma had elevated serum levels of CGRP. Seven of 24 patients with subacute thyroiditis had elevated serum levels of CGRP, but at least one year after clinical recovery, CGRP was undetectable in all. Seven of the 37 patients with hypothyroidism had elevated serum levels of CGRP. None of the patients with hyperthyroidism, adenomatous goiter, thyroid adenoma, or thyroid carcinoma had elevated serum CGRP levels. It is necessary to use a standard curve obtained by the addition of aprotinin and CGRP-free serum to the assay standards to measure serum CGRP levels. Some patients with subacute thyroiditis, hypothyroidism, or medullary thyroid carcinoma had elevated serum CGRP levels. (author)

  12. Localization of substance P, calcitonin gene related peptide and galanin in the nerve fibers of porcine cystic ovaries

    Directory of Open Access Journals (Sweden)

    Mariusz Majewski

    2012-01-01

    Full Text Available In a previous study, we showed that both the noradrenergic and cholinergic component of ovarian innervation is markedly changed in porcine cystic ovaries. The present study is aimed at elucidating the distribution pattern of substance P- (SP, calcitonin gene related peptide CGRP- and/or galanin (GAL-containing nerve fibers within porcine cystic ovaries. The status polycysticus was induced by dexamethasone phosphate disodium salt i.m. injections performed from the 7th until the 21st day of the first studied estrous cycle. During the same period of time, gilts of the control group received saline. All animals were slaughtered on the expected 11th day of the second studied estrous cycle, and their ovaries were collected. When compared to control gonad, a distinct difference in the distribution pattern and the density of SP-, CGRP- and/or GAL-immunoreactive (GAL-IR nerve fibers was observed. Thus, unlike in the control gonad, SP- and/or CGRP-IR perivascular nerve fibers were found to supply medullar blood vessels of polycystic ovary. Furthermore, the number of GAL-IR nerve fibers contributing to the ground plexus in polycystic ovaries was higher than that observed in the control gonads. Thus, as may be judged from the profound changes in the distribution pattern of differently chemically coded afferent terminals within polycystic gonads, it appears possible that neuropeptides released from these terminals may take part in the etiopathogenesis of this disorder. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 622–630

  13. Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs.

    Science.gov (United States)

    Ikegaki, I; Suzuki, Y; Satoh, S; Asano, T; Shibuya, M; Sugita, K

    1989-10-01

    The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 alpha (PGF2 alpha). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1-29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2 alpha-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.

  14. Healing of periodontal defects and calcitonin gene related peptide expression following inferior alveolar nerve transection in rats.

    Science.gov (United States)

    Lv, Linlin; Wang, Yanzhi; Zhang, Jing; Zhang, Ting; Li, Shu

    2014-06-01

    The roles of nerve and neuropeptides in the process of bone formation and remolding have been studied previously. However, the effects of nervous system and neuropeptide on periodontal alveolar bone formation remained unknown. The aim of this study was to assess the effect of innervation on regeneration of alveolar bone and expression levels of calcitonin gene related peptide (CGRP) in periodontal tissues of rats, so as to have a better understanding of the effect of nerve and its related neuropeptide on periodontal tissue regeneration. Rats received transection of the left inferior alveolar nerve and a surgery to produce bilateral periodontal defect, then the alveolar tissue was obtained from animals of each group at week 1, 2, 4, 6 and 8 weeks after operation, respectively. Hematoxylin and eosin staining, and Masson staining were performed to evaluate the ability to restore and repair periodontal tissues at 4, 6 and 8 after surgery. Then new bone formation area and mineralized area were quantified using imagepro-plus6.0 software after pictures were taken under the microscope and SPSS17.0 was used for statistical analysis. Immunohistochemical staining was applied to investigate the expression of CGRP at 1, 2, 4, 6 and 8 weeks. Rats received transection of the left inferior alveolar nerve surgery and were then sacrificed at day 1, 3, 7, 14, 21, 28 after the operation. The change of CGRP expression in periodontal tissue was detected using immunohistochemical methods. The results showed that the volume of new bone formation was not significantly difference between the experimental and control groups, but the mineralized new bone area between the two groups was statistically significant. The level of CGRP expression was lower than normal at week 1, and then it began to rise in the next stage. The plateau, at higher than normal level, was reached at 6 weeks post-surgery. Results of transection of the left inferior alveolar nerve demonstrated the expression of CGRP

  15. 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......) participate in the myogenic control of MCA diameter. The present study investigated the contribution of Kv7.4 and Kv7.5 isoforms to myogenic and CGRP regulation of MCA diameter and determined whether they were affected in hypertensive animals....

  16. 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

    OBJECTIVE: The objective of this study was to explore the role of K(ATP) channels in vasodilatation induced by calcitonin gene-related peptide (CGRP), nitric oxide (NO), and transcranial electrical stimulation (TES) in intracranial arteries of rat. BACKGROUND: Dilatation of cerebral and dural...... CGRP, NO, and endogenous CGRP after electrical stimulation. Also diameter changes of pial arteries, mean arterial blood pressure and local cerebral blood flow by Laser Doppler flowmetry (LCBF(Flux)) were measured. RESULTS: CGRP, NO, and TES caused dilatation of the 2 arteries in vivo and in vitro...

  17. 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; 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...

  18. Receptor Activity-modifying Protein-directed G Protein Signaling Specificity for the Calcitonin Gene-related Peptide Family of Receptors.

    Science.gov (United States)

    Weston, Cathryn; Winfield, Ian; Harris, Matthew; Hodgson, Rose; Shah, Archna; Dowell, Simon J; Mobarec, Juan Carlos; Woodlock, David A; Reynolds, Christopher A; Poyner, David R; Watkins, Harriet A; Ladds, Graham

    2016-10-14

    The calcitonin gene-related peptide (CGRP) family of G protein-coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in a Gα s -mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gα s and Gα q but also identify a Gα i component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMP-dependent signaling bias among the Gα s , Gα i , and Gα q/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms......CGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained...... at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of αCGRP in hypertension may have been previously underestimated....

  20. Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

    Science.gov (United States)

    Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

    2015-11-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala. © 2015 International

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

    Science.gov (United States)

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

    2000-08-04

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

  2. The spatiotemporal relationships between chondroitin sulfate proteoglycans and terminations of calcitonin gene related peptide and parvalbumin immunoreactive afferents in the spinal cord of mouse embryos.

    Science.gov (United States)

    Wang, Liqing; Yu, Chao; Wang, Jun; Zhao, Hui; Chan, Sun-On

    2017-08-10

    Chondroitin sulfate (CS) proteoglycans (PGs) are a family of complex molecules in the extracellular matrix and cell surface that regulate axon growth and guidance during development of the central nervous system. In this study, the expression of CSPGs was investigated in the mouse spinal cord at late embryonic and neonatal stages using CS-56 antibody. CS immunoreactivity was observed abundantly in ventral regions of spinal cord of embryonic day (E) 15 embryos. At E16 to E18, CS expression spread dorsally, but never reached the superficial layers of the dorsal horn. This pattern was maintained until postnatal day 4, the latest stage examined. Antibodies against calcitonin gene related peptide (CGRP) and parvalbumin (PV) were employed to label primary afferents from nociceptors and proprioceptors, respectively. CGRP-immunoreactive fibers terminated in the superficial regions of the dorsal horn where CSPGs were weakly expressed, whereas PV-immunoreactive fibers were found in CSPG-rich regions in the ventral horn. Therefore, we conclude that CS expression is spatiotemporally regulated in the spinal cord, which correlates to the termination of sensory afferents. This pattern suggests a role of CSPGs on patterning afferents in the spinal cord, probably through a differential response of axons to these growth inhibitory molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Prevention of stress- or nitric oxide donor-induced medication overuse headache by a calcitonin gene-related peptide antibody in rodents.

    Science.gov (United States)

    Kopruszinski, Caroline Machado; Xie, Jennifer Yanhua; Eyde, Nathan Mackenzie; Remeniuk, Bethany; Walter, Sarah; Stratton, Jennifer; Bigal, Marcelo; Chichorro, Juliana Geremias; Dodick, David; Porreca, Frank

    2017-05-01

    Objective The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. Methods Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP antibody. Cutaneous allodynia (CA) was used as an outcome measure and CGRP blood and cerebrospinal fluid (CSF) levels were measured. Results BLS and NO donor challenge evoked delayed, long-lasting CA selectively in rats that were previously treated with sumatriptan or morphine. BLS produced a significant increase in CGRP in the plasma, but not CSF, in animals that were previously exposed to sumatriptan compared to saline controls. TEV48125 did not modify baseline tactile thresholds or produce behavioral side effects, but significantly inhibited both BLS- and NO donor-induced CA in animals that were previously primed with sumatriptan or morphine; an isotype control protein that does not bind CGRP had no effect. Interpretation These data suggest that acute migraine medications may promote MOH in susceptible individuals through CGRP-dependent mechanisms and that anti-CGRP antibodies may be a useful clinical strategy for the treatment of MOH.

  4. Hydrogen sulfide inhibits opioid withdrawal-induced pain sensitization in rats by down-regulation of spinal calcitonin gene-related peptide expression in the spine.

    Science.gov (United States)

    Yang, Hai-Yu; Wu, Zhi-Yuan; Bian, Jin-Song

    2014-09-01

    Hyperalgesia often occurs in opioid-induced withdrawal syndrome. In the present study, we found that three hourly injections of DAMGO (a μ-opioid receptor agonist) followed by naloxone administration at the fourth hour significantly decreased rat paw nociceptive threshold, indicating the induction of withdrawal hyperalgesia. Application of NaHS (a hydrogen sulfide donor) together with each injection of DAMGO attenuated naloxone-precipitated withdrawal hyperalgesia. RT-PCR and Western blot analysis showed that NaHS significantly reversed the gene and protein expression of up-regulated spinal calcitonin gene-related peptide (CGRP) in naloxone-treated animals. NaHS also inhibited naloxone-induced cAMP rebound and cAMP response element-binding protein (CREB) phosphorylation in rat spinal cord. In SH-SY5Y neuronal cells, NaHS inhibited forskolin-stimulated cAMP production and adenylate cyclase (AC) activity. Moreover, NaHS pre-treatment suppressed naloxone-stimulated activation of protein kinase C (PKC) α, Raf-1, and extracellular signal-regulated kinase (ERK) 1/2 in rat spinal cord. Our data suggest that H2S prevents the development of opioid withdrawal-induced hyperalgesia via suppression of synthesis of CGRP in spine through inhibition of AC/cAMP and PKC/Raf-1/ERK pathways.

  5. 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

    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...... extracts, CGRP-LI corresponded entirely to porcine CGRP plus smaller amounts of oxidised CGRP. Using isolated vascularly perfused segments of the ileum, we studied the release of CGRP-LI in response to electrical stimulation of the mixed extrinsic periarterial nerves and to infusion of different...... receive excitatory input by parasympathetic, possibly vagal, preganglionic fibres, via release of acetylcholine acting on nicotinic receptors. The stimulatory effect of capsaicin suggests that CGRP is also released from extrinsic sensory neurons....

  6. Pulsed Radiofrequency Applied to the Sciatic Nerve Improves Neuropathic Pain by Down-regulating The Expression of Calcitonin Gene-related Peptide in the Dorsal Root Ganglion

    Science.gov (United States)

    Ren, Hao; Jin, Hailong; Jia, Zipu; Ji, Nan; Luo, Fang

    2018-01-01

    Background: Clinical studies have shown that applying pulsed radiofrequency (PRF) to the neural stem could relieve neuropathic pain (NP), albeit through an unclear analgesic mechanism. And animal experiments have indicated that calcitonin gene-related peptide (CGRP) expressed in the dorsal root ganglion (DRG) is involved in generating and maintaining NP. In this case, it is uncertain whether PRF plays an analgesic role by affecting CGRP expression in DRG. Methods: Rats were randomly divided into four groups: Groups A, B, C, and D. In Groups C and D, the right sciatic nerve was ligated to establish the CCI model, while in Groups A and B, the sciatic nerve was isolated without ligation. After 14 days, the right sciatic nerve in Groups B and D re-exposed and was treated with PRF on the ligation site. Thermal withdrawal latency (TWL) and hindpaw withdrawal threshold (HWT) were measured before PRF treatment (Day 0) as well as after 2, 4, 8, and 14 days of treatment. At the same time points of the behavioral tests, the right L4-L6 DRG was sampled and analyzed for CGRP expression using RT-qPCR and an enzyme-linked immunosorbent assay (ELISA). Results: Fourteen days after sciatic nerve ligation, rats in Groups C and D had a shortened TWL (P 0.05). On the 8th and 14th days, the mRNA levels in Group D were restored to those of Groups A and B. Meanwhile, the CGRP content of Group D gradually dropped over time, from 76.4 pg/mg (Day 0) to 57.5 pg/mg (Day 14). Conclusions: In this study, we found that, after sciatic nerve ligation, rats exhibited apparent hyperalgesia and allodynia, and CGRP mRNA and CGRP contents in the L4-L6 DRG increased significantly. Through lowering CGRP expression in the DRG, PRF treatment might relieve the pain behaviors of NP. PMID:29333099

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Olfactory identification in patients with schizophrenia - the influence of β-endorphin and calcitonin gene-related peptide concentrations.

    Science.gov (United States)

    Urban-Kowalczyk, M; Śmigielski, J; Strzelecki, D

    2017-03-01

    The relationship between the olfactory system and emotional processing is an area of growing interest in schizophrenia research. Both the orbitofrontal cortex and amygdala are involved in the processing of olfactory information, and olfactory deficits may be also influenced by endogenous opioids and calcitonin gene-related peptide (CGRP), which is probably involved in dopaminergic transmission. However, the relationship between endorphins and dopaminergic transmission has not been fully explored. Odor identification performance and valence interaction was evaluated among 50 schizophrenic patients and 50 controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). All study participants were subjected to the University of Pennsylvania Smell Identification Test (UPSIT), blood β-endorphin (BE) and CGRP measurement. Insignificantly higher BE concentrations were observed in the patient group, while significantly higher UPSIT scores were seen in controls (mean UPSIT 32.48 vs 26.82). The patients demonstrated significantly more identification errors for pleasant (P=0.000) and neutral (P=0.055) odors than for unpleasant odors. Patients with higher BE concentrations made more identification errors concerning pleasant (R s =-0.292; P=0.04) and neutral odors (R s =-0.331; P=0.019). Although the concentration of CGRP was significantly higher in the patient sample (Pidentification by valence for pleasant and neutral odors (UPSIT n/16: R s =-0.450, P=0.001; UPSIT n/15: R s =-0.586, P=0.000), and a weak negative correlation between PANSS N score and identification of unpleasant odors (UPSIT n/9: R s =-0.325, P=0.021). Schizophrenic patients present a unique pattern of smell identification characterized by aberrant hedonic ratings for pleasant odors but not unpleasant ones. Individuals with predominant negative symptoms and higher BE concentrations are most able to identify negative odors. Copyright © 2016 Elsevier Masson SAS. All rights

  9. Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP).

    Science.gov (United States)

    Karami, Masoume; Bathaie, S Zahra; Tiraihi, Taqi; Habibi-Rezaei, Mehran; Arabkheradmand, Jalil; Faghihzadeh, Soghrat

    2013-12-15

    Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (plocomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2±2.3 to 1140.3±4.5pg/ml due to SCI and reached 789.1±2.7pg/ml after crocin treatment. These changes were significant at the level of p<0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain. Copyright © 2013 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

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

    2015-09-01

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

  11. Calcitonin gene-related peptide and somatostatin releases correlated with the area under the lafutidine concentration-time curve in human plasma.

    Science.gov (United States)

    Ikawa, K; Shimatani, T; Azuma, Y; Inoue, M; Morikawa, N

    2006-08-01

    To examine the effects of the histamine H(2)-receptor antagonist, lafutidine, at clinical dosage (10 mg tablet after a standardized meal) on plasma levels of the gastrointestinal peptides, calcitonin gene-related peptide (CGRP), somatostatin and gastrin. Six healthy male volunteers ate a standardized meal, and received either lafutidine orally at a dose of 10 mg or water only (control). Blood samples were taken before and up to 4 h after the drug administration. Plasma lafutidine concentrations were determined by high pressure liquid chromatography. Pharmacokinetic analysis of lafutidine was performed using one-compartmental model. The levels of immunoreactive substances of plasma CGRP, somatostatin and gastrin were measured by enzyme immunoassay, and the amount of peptide release was calculated by the trapezoidal method. Lafutidine significantly increased plasma CGRP levels at 1, 1.5, 2.5 and 4 h and the total amount of CGRP release (192 +/- 14.0 pg.h/mL) compared with the control group (128 +/- 21.5 pg.h/mL). Lafutidine significantly increased the plasma somatostatin levels at 1 and 1.5 h, and the total amount of somatostatin released (107 +/- 18.2 pg.h/mL) compared with the control (78.4 +/- 7.70 pg.h/mL). The area under the drug concentration-time curve (AUC) from 0 to 4 h after administration correlated well with the Delta-CGRP and Delta-somatostatin release but not with total amount of gastrin released. However, plasma gastrin levels were significantly elevated at 1.5 h after drug administration. Lafutidine at clinical dosage increases plasma CGRP and the somatostatin. The amounts released correlated with the AUC of lafutidine in humans. These results suggest that the increased release of CGRP and somatostatin may contribute to its gastroprotective and anti-acid secretory effect.

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

    Directory of Open Access Journals (Sweden)

    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

  13. Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab

    Directory of Open Access Journals (Sweden)

    Giamberardino MA

    2017-12-01

    Full Text Available Maria Adele Giamberardino,1,* Giannapia Affaitati,1,* Raffaele Costantini,2 Francesco Cipollone,3,* Paolo Martelletti4,* 1Department of Medicine and Science of Aging, Headache Center, Geriatrics Clinic and Ce.S.I.-Met, “G. D’Annunzio” University of Chieti, Chieti, Italy; 2Department of Medical, Oral and Biotechnological Sciences, Institute of Surgical Pathology, “G. D’Annunzio” University of Chieti, Chieti, Italy; 3Department of Medicine and Science of Aging, Medical Clinic and Ce.S.I.-Met, “G. D’Annunzio” University of Chieti, Chieti, Italy; 4Department of Clinical and Molecular Medicine, Regional Referral Headache Center, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy *These authors contributed equally to this work Abstract: Migraine is a highly disabling neurological condition, and preventative treatment still remains problematic, due to aspecificity of the majority of the currently available prophylactic drugs. Calcitonin-gene-related peptide (CGRP plays a crucial role in migraine pathophysiology; agents aimed at blocking its activity have, therefore, been developed in recent years, among which are monoclonal antibodies (mAbs against CGRP, to prevent migraine. Erenumab is the only mAb that targets the CGRP receptor instead of the ligand, with high specificity and affinity of binding. This review will report on the most recent data on erenumab characteristics and on the results of clinical trials on its employment in the prevention of episodic migraine (4–14 monthly migraine days: one Phase II and two Phase III trials (completed and one Phase III trial (ongoing. Monthly subcutaneous administration (70 mg or 140 mg of erenumab vs placebo for 3–6 months showed significantly higher efficacy in reducing the mean monthly number of migraine days and the use of migraine-specific medication, and in decreasing physical impairment and impact of migraine on everyday activities (P<0.001. A favorable safety profile

  14. 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-rela...

  15. The effect and safety of monoclonal antibodies to calcitonin gene-related peptide and its receptor on migraine: a systematic review and meta-analysis.

    Science.gov (United States)

    Hou, Min; Xing, Haiyan; Cai, Yongqing; Li, Bin; Wang, Xianfeng; Li, Pan; Hu, Xiaolin; Chen, Jianhong

    2017-12-01

    Migraine has been recognized as one of the leading causes of disability in the 2013 Global Burden of Disease Study and seriously affects the quality of patients' life, current treatment options are not ideal. Monoclonal antibodies to calcitonin gene-related peptide and its receptor (CGRP-mAbs) appear more promising for migraine because of considerably better effect and safety profiles. The objective of this study is to systematically assess the clinical efficacy and safety of CGRP-mAbs for migraine therapy. A systematic literature search in PubMed, Cochrane Library and Baidu Scholar was performed to identify randomized controlled trials (RCTs), which compared the effect and safety of CGRP-mAbs with placebo on migraine. Regarding the efficacy, the reduction of monthly migraine days from baseline to weeks 1-4, 5-8, and 9-12; responder rates were extracted as the outcome measures of the effects of CGRP-mAbs. Regarding the safety, total adverse events, the main adverse events, and other adverse events were evaluated. We found significant reduction of monthly migraine days in CGRP-mAbs vs. placebo (weeks 1-4: SMD -0.49, 95% CI -0.61 to -0.36; weeks 5-8: SMD -0.43, 95% CI -0.56 to -0.30; weeks 9-12: SMD -0.37, 95% CI -0.49 to -0.24). 50% and 75% responder rates (OR 2.59, 95% CI 1.99 to 3.37; and OR 2.91, 95% CI 2.06 to 4.10) were significantly increased compared with placebo. There was no significant difference in total adverse events (OR 1.17, 95% CI 0.91 to 1.51), and the main adverse events including upper respiratory tract infection (OR 1.44, 95% CI 0.82 to 2.55), nasopharyngitis (OR 0.59, 95% CI 0.30 to 1.16), nausea (OR 0.61, 95% CI 0.29 to 1.32), injection-site pain (OR 1.73, 95% CI 0.95 to 3.16) and back pain (OR 0.97, 95% CI 0.49 to 1.90) were not obviously changed compared with placebo control, but the results showed significant increase of dizziness in CGRP-mAbs vs. placebo (OR 3.22, 95% CI 1.09 to 9.45). This meta-analysis suggests that CGRP-mAbs are

  16. mRNA expression of 5-hydroxytryptamine 1B, 1D, and 1F receptors and their role in controlling the release of calcitonin gene-related peptide in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, Dipak V; Ploug, Kenneth B; Hay-Schmidt, Anders

    2012-01-01

    Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the mRNA expres......Triptans, a family of 5-hydroxytryptamine (5-HT) 1B, 1D, and 1F receptor agonists, are used in the acute treatment of migraine attacks. The site of action and subtypes of the 5-HT(1) receptor that mediate the antimigraine effect have still to be identified. This study investigated the m......RNA expression of these receptors and the role of 5-HT(1) receptor subtypes in controlling the release of calcitonin gene-related peptide (CGRP) in rat dura mater, trigeminal ganglion (TG), and trigeminal nucleus caudalis (TNC). The mRNA for each receptor subtype was quantified by quantitative real...

  17. The Influence of Low Doses of Zearalenone and T-2 Toxin on Calcitonin Gene Related Peptide-Like Immunoreactive (CGRP-LI Neurons in the ENS of the Porcine Descending Colon

    Directory of Open Access Journals (Sweden)

    Krystyna Makowska

    2017-03-01

    Full Text Available The enteric nervous system (ENS can undergo adaptive and reparative changes in response to physiological and pathological stimuli. These manifest primarily as alterations in the levels of active substances expressed by the enteric neuron. While it is known that mycotoxins can affect the function of the central and peripheral nervous systems, knowledge about their influence on the ENS is limited. Therefore, the aim of the present study was to investigate the influence of low doses of zearalenone (ZEN and T-2 toxin on calcitonin gene related peptide-like immunoreactive (CGRP-LI neurons in the ENS of the porcine descending colon using a double immunofluorescence technique. Both mycotoxins led to an increase in the percentage of CGRP-LI neurons in all types of enteric plexuses and changed the degree of co-localization of CGRP with other neuronal active substances, such as substance P, galanin, nitric oxide synthase, and cocaine- and amphetamine-regulated transcript peptide. The obtained results demonstrate that even low doses of ZEN and T-2 can affect living organisms and cause changes in the neurochemical profile of enteric neurons.

  18. A Novel α-Calcitonin Gene-Related Peptide Analogue Protects Against End-Organ Damage in Experimental Hypertension, Cardiac Hypertrophy and Heart Failure

    DEFF Research Database (Denmark)

    Aubdool, Aisah A; Thakore, Pratish; Argunhan, Fulye

    2017-01-01

    cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist. The effect of the αAnalogue on Angiotensin II (AngII)-induced hypertension......, Western blot and histology. Results -The AngII-induced hypertension was attenuated by co-treatment with the αAnalogue (50nmol/kg/day, s.c., at a dose selected for lack of long term hypotensive effects at baseline). The αAnalogue protected against vascular, renal and cardiac dysfunction, characterised...... failure. It preserved heart function, assessed by echocardiography, whilst protecting against adverse cardiac remodelling and apoptosis. Moreover, treatment with the αAnalogue was well-tolerated with neither signs of desensitisation nor behavioural changes. Conclusions -These findings, in two distinct...

  19. Effects of glyceryl trinitrate and calcitonin-gene-related peptide on BOLD signal and arterial diameter –methodological studies by fMRI and MRA

    DEFF Research Database (Denmark)

    Asghar, Mohammed Sohail; Ashina, Messoud

    2013-01-01

    Over the last decades MRI has proved to be very useful in the field of drug development and discovery. Pharmacological MRI (phMRI) explores the interaction between brain physiology, neuronal activity and drugs[1]. The BOLD-signal is an indirect method to investigate brain activity by way...... of measuring task-related hemodynamic changes. Pharmacological substances that induce hemodynamic changes can therefore potentially alter the BOLD-signal that in turn falsely can be interpreted as changes in neuronal activity. It is therefore important to characterize possible effects of a pharmacological...... substance on the BOLD-response per see before that substance can be used in an fMRI experiment. Furthermore MR-angiography is useful in determining the vascular site-of-action of vasoactive substances....

  20. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

  1. Substance P and Calcitonin gene-related peptide expression in human periodontal ligament after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files.

    Science.gov (United States)

    Caviedes-Bucheli, J; Rios-Osorio, N; Rey-Rojas, M; Laguna-Rivero, F; Azuero-Holguin, M M; Diaz, L E; Curtidor, H; Castaneda-Ramirez, J J; Munoz, H R

    2018-05-17

    To quantify the Substance P (SP) and Calcitonin gene-related peptide (CGRP) expression in healthy human periodontal ligament from premolars after root canal preparation with Reciproc Blue, WaveOne Gold, XP EndoShaper and hand files. Fifty human periodontal ligament samples were obtained from healthy mandibular premolars where extraction was indicated for orthodontic reasons. Prior to extraction, 40 of these premolars were equally divided into four groups, and root canals were prepared using four different systems: Reciproc Blue, WaveOne Gold, XP EndoShaper, and a hand instrumentation technique. The remaining 10 healthy premolars were extracted without treatment and served as a negative control group. All periodontal ligament samples were processed, and SP and CGRP were measured by radioimmunoassay. The Kruskal-Wallis test was used to establish significant differences between groups and LSD post hoc comparisons were also performed. Greater SP and CGRP values were found in the hand instrumentation group, followed by the XP EndoShaper, WaveOne Gold and the Reciproc groups. The lower SP and CGRP values were for the healthy periodontal ligament group. The Kruskal-Wallis test revealed significant differences between groups (p 0.05). All the root canal preparation techniques tested increased SP and CGRP expression in human periodontal ligament, with hand files and XP EndoShaper instruments being associated with greater neuropeptide release compared to Reciproc Blue and WaveOne Gold files. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Effects of salmon calcitonin and calcitonin gene related peptide ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-04-20

    Apr 20, 2009 ... mucus and phospholipids in rats exposed to cold + restraint stress (CRS). .... and CGRP (10 µg/kg) were dissolved in sterile distilled water and injected ..... Liver. Physiol. 280: G470-G474. Allen A, Flemstrom G (2005).

  3. Effect of electroacupuncture on thermal pain threshold and expression of calcitonin-gene related peptide, substance P and γ-aminobutyric acid in the cervical dorsal root ganglion of rats with incisional neck pain.

    Science.gov (United States)

    Qiao, Li-Na; Liu, Jun-Ling; Tan, Lian-Hong; Yang, Hai-Long; Zhai, Xu; Yang, Yong-Sheng

    2017-08-01

    Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain. The pain model was established by making a longitudinal midline neck incision in 60 rats. Another 15 rats underwent sham surgery (normal group). Post-incision, 15 rats remained untreated (model group) and 45 rats underwent EA (frequency 2/100 Hz, intensity 1 mA) at bilateral LI18, LI4-PC6 or ST36-GB34 (n=15 each) for 30 min at 4 hours, 24 hours, and 48 hours post-surgery, followed by thermal pain threshold (PT) measurement. 30 min later, the rats were euthanased and cervical (C3-6) DRGs removed for measurement of immunoreactivity and mRNA expression of SP/CGRP and the GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67). Thermal PT was significantly lower in the model group versus the normal group and increased in the LI18 and LI4-PC6 groups but not the ST36-GB34 group compared with the model group. Additionally, EA at LI18 and LI4-PC6 markedly suppressed neck incision-induced upregulation of mRNA/protein expression of SP/CGRP, and upregulated mRNA/protein expression of GAD67 in the DRGs of C3-6 segments. EA at LI18/LI4-PC6 increases PT in rats with incisional neck pain, which is likely related to downregulation of pronociceptive mediators SP/CGRP and upregulation of the inhibitory transmitter GABA in the primary sensory neurons of cervical DRGs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Calcitonin blood test

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003699.htm Calcitonin blood test To use the sharing features on this page, please enable JavaScript. The calcitonin blood test measures the level of the hormone calcitonin in ...

  5. Assays for calcitonin receptors

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  6. Calcitonin Salmon Injection

    Science.gov (United States)

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

  7. Calcitonin Salmon Nasal Spray

    Science.gov (United States)

    Calcitonin salmon is used to treat osteoporosis in women who are at least 5 years past menopause and cannot ... a human hormone that is also found in salmon. It works by preventing bone breakdown and increasing ...

  8. Calcitonin gene-related peptide and migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Ashina, Messoud

    2014-01-01

    on CGRP and MA. METHODS: We performed a systematic literature search on MEDLINE for reports of CGRP and MA, covering basic science, animal and human studies as well as randomized clinical trials. RESULTS: The literature search identified 594 citations, of which 38 contained relevant, original data. Plasma...

  9. Increased circulating calcitonin in cirrhosis. Relation to severity of disease and calcitonin gene-related peptide

    DEFF Research Database (Denmark)

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

    2000-01-01

    circulating plasma concentrations of CT in patients with cirrhosis in relation to the severity of disease and the plasma level of CGRP. Moreover, the kinetics of CT was evaluated for different organ systems by determination of arteriovenous extraction. Thirty-nine patients with cirrhosis (Child...... system, lower extremities, or peripheral circulation, but there was a substantial rate of pulmonary disposal and clearance (P

  10. Digital gene expression analysis of corky split vein caused by boron deficiency in 'Newhall' Navel Orange (Citrus sinensis Osbeck for selecting differentially expressed genes related to vascular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Cheng-Quan Yang

    Full Text Available Corky split vein caused by boron (B deficiency in 'Newhall' Navel Orange was studied in the present research. The boron-deficient citrus exhibited a symptom of corky split vein in mature leaves. Morphologic and anatomical surveys at four representative phases of corky split veins showed that the symptom was the result of vascular hypertrophy. Digital gene expression (DGE analysis was performed based on the Illumina HiSeq™ 2000 platform, which was applied to analyze the gene expression profilings of corky split veins at four morphologic phases. Over 5.3 million clean reads per library were successfully mapped to the reference database and more than 22897 mapped genes per library were simultaneously obtained. Analysis of the differentially expressed genes (DEGs revealed that the expressions of genes associated with cytokinin signal transduction, cell division, vascular development, lignin biosynthesis and photosynthesis in corky split veins were all affected. The expressions of WOL and ARR12 involved in the cytokinin signal transduction pathway were up-regulated at 1(st phase of corky split vein development. Furthermore, the expressions of some cell cycle genes, CYCs and CDKB, and vascular development genes, WOX4 and VND7, were up-regulated at the following 2(nd and 3(rd phases. These findings indicated that the cytokinin signal transduction pathway may play a role in initiating symptom observed in our study.

  11. Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

    Directory of Open Access Journals (Sweden)

    Abimael González-Hernández

    2016-01-01

    Full Text Available Calcitonin gene-related peptide (CGRP is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP, the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor. This receptor is an atypical G-protein coupled receptor (GPCR composed of three functional proteins: (i the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein, (ii the activity-modifying protein type 1 (RAMP1, and (iii a receptor component protein (RCP. Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia. The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

  12. Calcitonin produces hypercalcemia in leopard sharks.

    Science.gov (United States)

    Glowacki, J; O'Sullivan, J; Miller, M; Wilkie, D W; Deftos, L J

    1985-02-01

    Calcitonin was detected by RIA in sera from four marine species, leopard sharks (Triakis semifasciata), horn sharks (Heterodontus francisci), thornback rays (Platyrhinoides triseriata), and kelp bass (Paralabrax clathratus). These animals have levels of calcitonin and calcium higher than freshwater and terrestrial species have. The administration of salmon calcitonin to bass (4 micrograms/kg BW) produced hypocalcemia and hypophosphatemia as has been reported for other bony vertebrates. In marked contrast, calcitonin produced a prompt hypercalcemia in sharks; the average was 9.8% increase in serum calcium in nine animals with no attendant change in phosphorus. These findings demonstrate that calcitonin can increase serum calcium in sharks. Because shark skeleton is composed of cartilage, this hypercalcemic effect of calcitonin does not require a bony skeleton.

  13. Indirect evidence of calcitonin secretion in man.

    Science.gov (United States)

    Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R

    1976-09-01

    1. The effect of calcitonin, a large amount of calcium given orally, pentagastrin and glucagon on plasma 47Ca radioactivity curves in subjects pretreated with 47Ca was examined. 2. A sudden increase of plasma radioactivity after intravenous administration of calcitonin and pentagastrin and after the oral calcium load was observed in normal subjects; the intravenous infusion of glucagon was less effective. 3. Two thyroparathyroidectomized patients who responded to the calcitonin infusion did not respond to the oral calcium load. 4. These data may be considered to offer indirect evidence of endogenous calcitonin secretion in man.

  14. Calcitonin

    Science.gov (United States)

    ... Disorders Fibromyalgia Food and Waterborne Illness Fungal Infections Gout Graves Disease Guillain-Barré Syndrome Hashimoto Thyroiditis Heart ... related to an inherited mutation in the RET gene that leads to multiple endocrine neoplasia type 2 ( ...

  15. STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition.

    Science.gov (United States)

    Terra, Silvia R; Cardoso, João Carlos R; Félix, Rute C; Martins, Leo Anderson M; Souza, Diogo Onofre G; Guma, Fatima C R; Canário, Adelino Vicente M; Schein, Vanessa

    2015-03-05

    Stanniocalcin 1 (STC1) and calcitonin gene-related peptide (CGRP) are involved in bone formation/remodeling. Here we investigate the effects of STC1 on functional heterodimer complex CALCRL/RAMP1, expression and activity during osteoblastogenesis. STC1 did not modify CALCRL and ramp1 gene expression during osteoblastogenesis when compared to controls. However, plasma membrane spatial distribution of CALCRL/RAMP1 was modified in 7-day pre-osteoblasts exposed to either CGRP or STC1, and both peptides induced CALCRL and RAMP1 assembly. CGRP, but not STC1 stimulated cAMP accumulation in 7-day osteoblasts and in CALCRL/RAMP1 transfected HEK293 cells. Furthermore, STC1 inhibited forskolin stimulated cAMP accumulation of HEK293 cells, but not in CALCRL/RAMP1 transfected HEK293 cells. However, STC1 inhibited cAMP accumulation in calcitonin receptor (CTR) HEK293 transfected cells stimulated by calcitonin. In conclusion, STC1 signals through inhibitory G-protein modulates CGRP receptor spatial localization during osteoblastogenesis and may function as a regulatory factor interacting with calcitonin peptide members during bone formation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Pharmacological characterization of receptor-activity-modifying proteins (RAMPs) and the human calcitonin receptor.

    Science.gov (United States)

    Armour, S L; Foord, S; Kenakin, T; Chen, W J

    1999-12-01

    Receptor-activity-modifying proteins (RAMPs) are a family of single transmembrane domain proteins shown to be important for the transport and ligand specificity of the calcitonin gene-related peptide (CGRP) receptor. In this report, we describe the analysis of pharmacological properties of the human calcitonin receptor (hCTR) coexpressed with different RAMPs with the use of the Xenopus laevis melanophore expression system. We show that coexpression of RAMP3 with human calcitonin receptor changed the relative potency of hCTR to human calcitonin (hCAL) and rat amylin. RAMP1 and RAMP2, in contrast, had little effect on the change of hCTR potency to hCAL or rat amylin. When coexpressed with RAMP3, hCTR reversed the relative potency by a 3.5-fold loss in sensitivity to hCAL and a 19-fold increase in sensitivity to rat amylin. AC66, an inverse agonist, produced apparent simple competitive antagonism of hCAL and rat amylin, as indicated by linear Schild regressions. The potency of AC66 was changed in the blockade of rat amylin but not hCAL responses with RAMP3 coexpression. The mean pK(B) for AC66 to hCAL was 9.4 +/- 0.3 without RAMP3 and 9.45 +/- 0.07 with RAMP3. For the antagonism of AC66 to rat amylin, the pK(B) was 9.25 +/- 0.15 without RAMP3 and 8.2 +/- 0.35 with RAMP3. The finding suggests that RAMP3 might modify the active states of calcitonin receptor in such a way as to create a new receptor phenotype that is "amylin-like." Irrespective of the physiological association of the new receptor species, the finding that a coexpressed membrane protein can completely change agonist and antagonist affinities for a receptor raises implications for screening in recombinant receptor systems.

  17. Determination of calcitonin; Bestimmung von Kalzitonin

    Energy Technology Data Exchange (ETDEWEB)

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

    2005-03-01

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

  18. Additive phosphaturic action of parathyrin and calcitonin

    International Nuclear Information System (INIS)

    Oberleitner, H.; Lang, F.; Greger, P.; Sporer, H.; Deetjen, P.

    1980-01-01

    Parathyrin and calcitonin exert their effects on phosphate metabolism by influencing the functions of at least three organ systems, i.e. bone, gut and kidneys. To study the renal effects of these hormones under exclusion of systemic effects microinfusion studies were performed in anesthetised rats. After thyroparathyroidectomy radioactively labelled phosphate containing solutions were microinfused into single proximal convoluted tubules. The tracer recovery in the urine allowed calculation of phosphate reabsorption in the nephron segments beyond the micropuncture site. After a control period of 6 minutes the hormones were superfused to the nephron surface and tracer recovery measured during the following 36 minutes. Within few minutes both, parathyrin and calcitonin, clearly reduced phosphate reabsorption. Infusions of supramaximal doses of either hormone abolished the local action of this hormone but did not influence the effect of the other. Thus the phosphaturic actions of parathyrin and calcitonin are additive, indicating that the hormones involve different mechanisms and/or nephron sites. (author)

  19. Re-examination of human calcitonin radioimmunoassay

    International Nuclear Information System (INIS)

    Argemi, B.; Hours, M.C.; Even, F.; Garguilo, G.; Hollard, J.M.

    1978-01-01

    Evaluations of human immunoreactive calcitonin (IRCT) assay have been extensively reviewed. Labelled hormone was re-purified on carboxy-methyl-cellulose in order to isolate a fraction containing mainly monoiodinated calcitonin, which was found to be very stable. Two antisera with different immunochemical characteristics were used for incubation studies, one of which was incubated with unextracted and extracted plasma samples. The sensitivity of the assays was 60 pg/ml plasma. However, marked differences were observed in the results obtained by the three methods depending on the importance of the inhibitory effect of plasma on the binding of the tracer to antibodies. However, the absolute plasma IRCT level could not be related to the presence of calcitonin M, except in one case. Further studies are needed in order to ascertain the origin and the significance of the immunoreactive material which was detected in normal plasma by one antiserum. (author)

  20. [Treatment of Sudeck's syndrome with human calcitonin].

    Science.gov (United States)

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

    1983-08-26

    Human calcitonin (Cibacalcin), at a dose of 0.5 mg daily for 15 days followed by 0.5 mg every other day for 4-6 months, was administered to 11 patients (eight men and three women, aged 36-74 years) with posttraumatic reflex sympathetic dystrophy of the lower limbs (stage I-II). Within one month there was significant lessening of pain, improved mobility and less oedema. Biochemical tests were within normal limits before and after treatment, while the pre-treatment raised bone retention of 99mTc-methylene-diphosphonate and increased blood flow in the affected area became normal during treatment. In nine patients healing occurred in the course of four to six months on treatment, in two patients after more than six months. There were no serious side-effects requiring interruption of treatment. These results indicate that human calcitonin should be tried in the treatment of this condition.

  1. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dugard, J; Kew, M C; Da Fonseca, M; Levin, J [University of the Witwatersrand, Johannesburg (South Africa)

    1982-08-21

    Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

  2. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Dugard, J.; Kew, M.C.; Da Fonseca, M.; Levin, J.

    1982-01-01

    Having found raised serum calcitonin concentrations is 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1 650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35,5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2 179 pg/ml). If 1 000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma

  3. RIA for calcitonin detection in human serum

    International Nuclear Information System (INIS)

    Mander, M.

    1977-01-01

    A RIA for human calcitonin (HCT) was adapted to the microtiter system. The method had a sensitivity of 60 pmol/l which is, however, not sufficient for measurements of the HCT level in healthy persons. Oral and i.v. administration of calcium, oral administration of vitamin D, and glucose tolerance tests did not result in a calcitonin increase over the detection limit. In two patients with histologically confirmed medullary thyroid carcinoma, there are extremely increased calcitonin levels: 16,000 and 120,000 pmol/l. In two other patients with medullary thyroid carcinoma after total resection of the thyroid, HCT levels were below the detection limit. In patients with hypercalcaemia (tumor hypercalcaemia), increased HCT levels were not observed. On the other hand, a HCT value of 150 pmol/l was found in a patient with vitamin D intoxication. As is normal in tumour cases of this kind, the two patients with medullar thyroid carcinoma examined during the study suffered from severe diarrhoea. In both cases, the family anamnesis showed that the mothers of the two patients had also suffered from thyroid cancer. (orig.) [de

  4. 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.

  5. Comparison of the effects of salmon calcitonin (sCT) and calcitonin gene-related peptide (CGRP) in a number of in vivo and in vitro tests

    International Nuclear Information System (INIS)

    Welch, S.P.; Brase, D.; Cooper, C.; Dewey, W.L.

    1986-01-01

    sCT and CGRP have been shown previously to have multiple activities in the central nervous system (CNS). Recent work has shown that CGRP (15 μg) intraventricularly (IVT) produces a naloxone reversible 37% inhibition in the p-phenylquinone test (PPQ) accompanied by severe diarrhea. The ED50 of sCT in the PPQ test is 362 ng and this effect is not reversed totally by naloxone. The onset of CGRP is more rapid than that of sCT. sCT and CGRP (10 -6 M) both produce naloxone reversible inhibition of the electrically stimulated guinea pig ileum (GPI) (25% and 50% respectively). Both sCT and CGRP (10 -6 M) produce contracture (15% and 40% respectively) of the non-stimulated GPI that is not blocked by atropine. Both sCT and CGRP block the naloxone-induced contracture of the morphine (MS04) dependent ilea (29% and 68% respectively). Both sCT and CGRP produce biphasic shifts in the MS04 acetylcholine dose-effect curves in the stimulated and nonstimulated GPI, respectively. Neither sCT nor CGRP (10 -9 to 10 -4 M) displaces 3 H-naloxone binding to mouse brain membranes. Both sCT and CGRP may produce their effects by modulation of CA +2 fluxes in the CNS and GPI

  6. Induction of hypocalcemia by intracerebroventricular injection of calcitonin: evidence for control of blood calcium by the nervous system.

    Science.gov (United States)

    Goltzman, D; Tannenbaum, G S

    1987-07-21

    Calcitonin (CT), when administered peripherally, is a potent hypocalcemic agent. This peptide can also exert a variety of profound effects through brain receptors after central injection. We examined the capacity of CT to alter plasma calcium of freely moving conscious rats after intracerebroventricular (i.c.v.) injection. A dose-dependent decrease in plasma calcium was seen after administration of 25 ng, 250 ng or 2500 ng of salmon calcitonin (sCT). The extent and duration of hypocalcemia after central injection was equal to, or greater than, that seen after giving the same doses of peptide intravenously (i.v.). Calcitonin gene-related peptide (CGRP), when administered centrally at a 50-fold molar excess, produced only a transient decrease in plasma calcium. No increase in plasma levels of sCT could be detected by RIA after i.c.v. injection, although measurable levels were obtained by i.v. injection. Centrally administered sCT did not appear to produce hypocalcemia by enhancing the release of endogenous rat CT. In contrast to the rise in rat immunoreactive parathyroid hormone (PTH) seen after i.v. injection of sCT, no significant elevation occurred after central administration of the peptide despite induction of comparable levels of hypocalcemia. Consequently, reduced PTH release may contribute to the central hypocalcemic action of CT. The results indicate that peptides acting through the brain CT receptor may modulate peripheral blood calcium.

  7. Calcitonin and parathyroid hormone in blood serum of cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Tkacheva, G A; Kirsanov, A G; Burenin, I S [Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr

    1982-01-01

    A comparative radiommunoassay in the ratio of calcitonin and parathyroid hormone secretion was carried out in healthy controls (young and older than 40 years), patients with benign tumors, inflamatory processes and malignancies of the stomach, kidney, breast, prostate and lung. A significant increase in the ''calcitonin index'' (ratio of molar concentrations of calcitonin and parathyroid hormone) was established in patients with cancer of the breast, prostate and skeletal metastases of lung cancer, irrespective of the presence of primary tumor. This index is irrelevant in cases of gastric and renal carcinoma and cannot be used as indication of skeletal dissemination because of the predominant level of parathyroid hormone secretion.

  8. Phytoestrogens Enhance the Vascular Actions of the Endocannabinoid Anandamide in Mesenteric Beds of Female Rats

    Directory of Open Access Journals (Sweden)

    Roxana N. Peroni

    2012-01-01

    Full Text Available In rat isolated mesenteric beds that were contracted with NA as an in vitro model of the vascular adrenergic hyperactivity that usually precedes the onset of primary hypertension, the oral administration (3 daily doses of either 10 mg/kg genistein or 20 mg/kg daidzein potentiated the anandamide-induced reduction of contractility to NA in female but not in male rats. Oral treatment with phytoestrogens also restored the vascular effects of anandamide as well as the mesenteric content of calcitonin gene-related peptide (CGRP that were reduced after ovariectomy. The enhancement of anandamide effects caused by phytoestrogens was prevented by the concomitant administration of the estrogen receptor antagonist fulvestrant (2.5 mg/kg, s.c., 3 daily doses. It is concluded that, in the vasculature of female rats, phytoestrogens produced an estrogen-receptor-dependent enhancement of the anandamide-vascular actions that involves the modulation of CGRP levels and appears to be relevant whenever an adrenergic hyperactivity occurs.

  9. 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 second study. After a washing-out period of 2 weeks the participants were given 200 IE of sCT at the reverse time of the day 5 days prior to and during the third study. At all timepoints, urinary CrossLaps/Cr exhibited a significant (p

  10. Immunochemical heterogeneity of calcitonin in man: effect on radioimmunoassay

    International Nuclear Information System (INIS)

    Snider, R.H.; Moore, C.F.

    1977-01-01

    Determinations of blood levels of human calcitonin by radioimmunoassay have varied considerably in different laboratories. Much of the controversy over calcitonin levels can be attributed to the multiplicity of immunoreactive forms of the hormone (iCT), the differing region specificities of the antisera utilized for measurement by radioimmunoassay, protein effects, different rates of degradation of the various iCT fractions and the specific methodology of the radioimmunoassay

  11. 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

    , Western blot technique was used to demonstrate the existence of CGRP receptor components in rat SPG. CGRP immunoreactive fibers were frequently found intraganglionic in the SPG in the vicinity of neurons. CLR immunoreactivity was observed in satellite glial cells (SGCs) as well as in nerve fibers......, but not in neurons. RAMP1 immunoreactivity was localized in many neurons and SGCs. Thus, the two CGRP receptor components together were found in the SGCs. In addition, Western blot revealed the presence of RAMP1 and CLR in rat SPG. Our results suggest a possible sensory influence in the parasympathetic cranial...

  12. 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

    was found in the two tissues. The adrenal peptide was sequenced and found to differ from human alpha-CGRP at six positions and from human beta-CGRP at three positions. By immunohistochemistry, CGRP was found in nerve fibers in the pancreatic ganglia. A synthetic replica of the porcine peptide was infused...... significantly by 10(-8) M CGRP. In immunoneutralization studies (n = 6) using a high-affinity somatostatin antibody, the inhibitory effect of CGRP at 10(-8) M was reversed to a significant stimulation of insulin and glucagon secretion. Insulin secretion in response to square-wave increases in glucose...

  13. Fmoc Solid-Phase Synthesis of Human a-Calcitonin Gene- Related Peptide and Two Carboxyfluorescein-labeled Analogs

    DEFF Research Database (Denmark)

    Ahmed, L. Sabbah; Abdolalizadeh, Bahareh; Sheykhzade, Majid

    for biological activity and onset of signal transduction. Fluorescent h-alpha-CGRP analogs are useful for investigating the mechanism of action behind (re)uptake of h-alpha-CGRP into the sensory nerve terminals and monitoring trafficking of CGRP receptors. As part of an ongoing study on the mechanism of action...

  14. The analgesic agent tapentadol inhibits calcitonin gene-related peptide release from isolated rat brainstem via a serotonergic mechanism.

    Science.gov (United States)

    Greco, Maria Cristina; Navarra, Pierluigi; Tringali, Giuseppe

    2016-01-15

    In this study we tested the hypothesis that tapentadol inhibits GGRP release from the rat brainstem through a mechanism mediated by the inhibition of NA reuptake; as a second alternative hypothesis, we investigated whether tapentadol inhibits GGRP release via the inhibition of 5-HT reuptake. Rat brainstems were explanted and incubated in short-term experiments. CGRP released in the incubation medium was taken as a marker of CGRP release from the central terminals of trigeminal neurons within the brainstem. CGRP levels were measured by radioimmunoassay under basal conditions or in the presence of tapentadol; NA, 5-HT, clonidine, yohimbine and ondansetron were used as pharmacological tools to investigate the action mechanism of tapentadol. The α2-antagonist yohimbine failed to counteract the effects of tapentadol. Moreover, neither NA nor the α2-agonist clonidine per se inhibited K(+)-stimulated CGRP release, thereby indicating that the effects of tapentadol are nor mediated through the block of NA reuptake. Further experiments showed that 5-HT and tramadol, which inhibits both NA and 5-HT reuptake, significantly reduced K(+)-stimulated CGRP release. Moreover, the 5-HT3 antagonist ondansetron was able to counteract the effects of tapentadol in this system. This study provided pharmacological evidence that tapentadol inhibits stimulated CGRP release from the rat brainstem in vitro through a mechanism involving an increase in 5-HT levels in the system and the subsequent activation of 5-HT3 receptors. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. How Glycosaminoglycans Promote Fibrillation of Salmon Calcitonin*

    Science.gov (United States)

    Malmos, Kirsten Gade; Bjerring, Morten; Jessen, Christian Moestrup; Nielsen, Erik Holm Toustrup; Poulsen, Ebbe T.; Christiansen, Gunna; Vosegaard, Thomas; Skrydstrup, Troels; Enghild, Jan J.; Pedersen, Jan Skov; Otzen, Daniel E.

    2016-01-01

    Glycosaminoglycans (GAGs) bind all known amyloid plaques and help store protein hormones in (acidic) granular vesicles, but the molecular mechanisms underlying these important effects are unclear. Here we investigate GAG interactions with the peptide hormone salmon calcitonin (sCT). GAGs induce fast sCT fibrillation at acidic pH and only bind monomeric sCT at acidic pH, inducing sCT helicity. Increasing GAG sulfation expands the pH range for binding. Heparin, the most highly sulfated GAG, binds sCT in the pH interval 3–7. Small angle x-ray scattering indicates that sCT monomers densely decorate and pack single heparin chains, possibly via hydrophobic patches on helical sCT. sCT fibrillates without GAGs, but heparin binding accelerates the process by decreasing the otherwise long fibrillation lag times at low pH and accelerates fibril growth rates at neutral pH. sCT·heparin complexes form β-sheet-rich heparin-covered fibrils. Solid-state NMR reveals that heparin does not alter the sCT fibrillary core around Lys11 but makes changes to Val8 on the exterior side of the β-strand, possibly through contacts to Lys18. Thus GAGs significantly modulate sCT fibrillation in a pH-dependent manner by interacting with both monomeric and aggregated sCT. PMID:27281819

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  17. Calcitonin and calcitonin receptor-like receptors: common themes with family B GPCRs?

    Science.gov (United States)

    Barwell, James; Gingell, Joseph J; Watkins, Harriet A; Archbold, Julia K; Poyner, David R; Hay, Debbie L

    2012-05-01

    The calcitonin receptor (CTR) and calcitonin receptor-like receptor (CLR) are two of the 15 human family B (or Secretin-like) GPCRs. CTR and CLR are of considerable biological interest as their pharmacology is moulded by interactions with receptor activity-modifying proteins. They also have therapeutic relevance for many conditions, such as osteoporosis, diabetes, obesity, lymphatic insufficiency, migraine and cardiovascular disease. In light of recent advances in understanding ligand docking and receptor activation in both the family as a whole and in CLR and CTR specifically, this review reflects how applicable general family B GPCR themes are to these two idiosyncratic receptors. We review the main functional domains of the receptors; the N-terminal extracellular domain, the juxtamembrane domain and ligand interface, the transmembrane domain and the intracellular C-terminal domain. Structural and functional findings from the CLR and CTR along with other family B GPCRs are critically appraised to gain insight into how these domains may function. The ability for CTR and CLR to interact with receptor activity-modifying proteins adds another level of sophistication to these receptor systems but means careful consideration is needed when trying to apply generic GPCR principles. This review encapsulates current thinking in the realm of family B GPCR research by highlighting both conflicting and recurring themes and how such findings relate to two unusual but important receptors, CTR and CLR. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  18. [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.

  19. Effects of salmon calcitonin on fracture healing in ovariectomized rats.

    Science.gov (United States)

    Li, Xiaolin; Luo, Xinle; Yu, Nansheng; Zeng, Bingfang

    2007-01-01

    To explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats. We performed this study in The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China, during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had sham-operation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 sham-operated rats served as control group. After the fracture the rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing. Compared with OVX rats treated with normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (pnormalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also enhance the bone biomechanical properties and improve the process of fracture healing in fractured osteoporotic bone.

  20. Radioimmunoassay of calcitonin in plasma and cerebro-spinal fluid

    International Nuclear Information System (INIS)

    Cecchettin, M.; Comberti, E.; Quinzanini, M.; Albertini, A.; Tarquini, B.

    1985-01-01

    Some problems are discussed which, in analyzing the result of radioimmunoassay of calcitonin (CT), have to be taken into account regarding the standards used, the radioiodination, the antisere, if the assay was performed with or without extraction, the methode of extraction and the quality control. (H.W.). 11 refs.; 5 figs.; 4 tabs

  1. Effects of salmon calcitonin on fracture healing in ovariectomized rats

    International Nuclear Information System (INIS)

    Li, Xiaolin; Zeng, Bingfang; Luo, Xinle; Yu, Nansheng

    2007-01-01

    Objective was to explore the effects of salmon calcitonin on the healing process of osteoporotic fractures in ovariectomized rats. We performed this study in the First Affiliated Hospital of Guangzhaou Medical College, Guangzhaou, China during the period March 2002 to December 2004. We used 120 female adult Wistar rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other 30 had shamoperation. All rats had their left tibias fractured 3 months later. The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30 shamoperated rats served as control group. After the fracture rats had subcutaneous injection of normal saline, salmon calcitonin and estrogen, respectively. X-ray film, histological examination, bone mineral density (BMD) measurement and biomechanics testing were carried out to evaluate the fracture healing. Compared with OVX rats treated normal saline, the rats with salmon calcitonin had significantly higher BMD values in the left tibia, higher max torque, shear stress of the left tibia 8 weeks after fracture (p<0.05), and presented with stronger callus formation, shorter fracture healing time and faster normalization of microstructure of bone trabeculae. Salmon calcitonin can, not only increase in osteoporotic bone biomechanical properties and improve the process of fractured osteoporotic bone. (author)

  2. Calcitonin, phosphate, and the osteocyte--osteoblast bone cell unit

    Energy Technology Data Exchange (ETDEWEB)

    Talmage, R.V.; Matthews, J.L.; Martin, J.H.; Kennedy, J.W. III; Davis, W.L.; Roycroft, J.H. Jr.

    1974-01-01

    In this report we have attempted to correlate the morphological and chemical changes that occur in the long bone (tibia) of rats with the hypocalcemia that is produced following calcitonin injection or release from its gland of origin. By varying the supply of phosphate available to the rat, it has been possible to demonstrate that changes produced by CT both in bone and in plasma calcium concentrations were dependent upon an adequate supply of this ion. It is, therefore, postulated that the hypocalcemia produced by calcitonin is secondary to the formation of a calcium phosphate complex in and around osteocytes and lining cells. It is suggested that this complex, which is normally prevented from transforming to apatite crystal by the presence of an inhibitor, reduces the availability of calcium for rapid transport to the ECF. The reduction in calcium flux from bone to ECF results in a rapid and transient hypocalcemia. Regardless of the status of this postulate, we have at least demonstrated that the osteocyte-osteoblast unit of compact bone reacts rapidly to calcitonin in a process requiring phosphate in a sequence of events which can be closely correlated to the hypocalcemic action of the hormone.

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

    Directory of Open Access Journals (Sweden)

    Pedersen Christian

    2010-04-01

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

  4. Sugarcane genes related to mitochondrial function

    Directory of Open Access Journals (Sweden)

    Fonseca Ghislaine V.

    2001-01-01

    Full Text Available Mitochondria function as metabolic powerhouses by generating energy through oxidative phosphorylation and have become the focus of renewed interest due to progress in understanding the subtleties of their biogenesis and the discovery of the important roles which these organelles play in senescence, cell death and the assembly of iron-sulfur (Fe/S centers. Using proteins from the yeast Saccharomyces cerevisiae, Homo sapiens and Arabidopsis thaliana we searched the sugarcane expressed sequence tag (SUCEST database for the presence of expressed sequence tags (ESTs with similarity to nuclear genes related to mitochondrial functions. Starting with 869 protein sequences, we searched for sugarcane EST counterparts to these proteins using the basic local alignment search tool TBLASTN similarity searching program run against 260,781 sugarcane ESTs contained in 81,223 clusters. We were able to recover 367 clusters likely to represent sugarcane orthologues of the corresponding genes from S. cerevisiae, H. sapiens and A. thaliana with E-value <= 10-10. Gene products belonging to all functional categories related to mitochondrial functions were found and this allowed us to produce an overview of the nuclear genes required for sugarcane mitochondrial biogenesis and function as well as providing a starting point for detailed analysis of sugarcane gene structure and physiology.

  5. Calcitonin serum levels in normal and in pathological conditions

    International Nuclear Information System (INIS)

    Ziliotto, D.; Luisetto, G.; Zanatta, G.P.; Cataldi, F.; Zangari, M.; Gangemi, M.; Melanotte, P.L.; Caira, S.

    1985-01-01

    Radioimmunoassay of calcitonin (CT) gives variable results because of differences in sensitivity and specificity of antibody preparations and because of the known immunoheterogeneity of circulating CT. The difficulties in interpretation of data has hindered our understanding of normal and abnormal CT physiology. The authors separated the biologically active CT monomer (CTm) from the higher molecular weight biologically inactive forms before RIA. It makes it possible to re-evaluate the behaviour of CT in physiological conditions and to study its changes in diseases in which bone and mineral metabolism are in some way compromised. (Auth.)

  6. The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas.

    Science.gov (United States)

    Benes, L; Kappus, C; McGregor, G P; Bertalanffy, H; Mennel, H D; Hagner, S

    2004-02-01

    Gliomas are the most common primary tumours of the central nervous system and exhibit rapid growth that is associated with neovascularisation. Adrenomedullin is an important tumour survival factor in human carcinogenesis. It has growth promoting effects on gliomas, and blockade of its actions has been experimentally shown to reduce the growth of glioma tissues and cell lines. There is some evidence that the calcitonin receptor-like receptor (CRLR) mediates the tumorigenic actions of adrenomedullin. To determine whether CRLR is expressed in human gliomas and the probable cellular targets of adrenomedullin. Biopsies from 95 human gliomas of varying grade were processed for immunohistochemical analysis using a previously developed and characterised antibody to CRLR. All tumour specimens were positive for CRLR. As previously found in normal peripheral tissues, CRLR immunostaining was particularly intense in the endothelial cells. This was evident in all the various vascular conformations that were observed, and which are typical of gliomas. In addition, clear immunostaining of tumour cells with astrocyte morphology was observed. These were preferentially localised around vessels. This study has shown for the first time that the CRLR protein is present in human glioma tissue. The expression of the receptor in endothelial cells and in astrocytic tumour cells is consistent with the evidence that its endogenous ligand, adrenomedullin, may influence glioma growth by means of both direct mitogenic and indirect angiogenic effects. CRLR may be a valuable target for effective therapeutic intervention in these malignant tumours.

  7. Vascular remodeling versus amyloid beta-induced oxidative stress in the cerebrovascular dysfunctions associated with Alzheimer's disease.

    Science.gov (United States)

    Tong, Xin-Kang; Nicolakakis, Nektaria; Kocharyan, Ara; Hamel, Edith

    2005-11-30

    The roles of oxidative stress and structural alterations in the cerebrovascular dysfunctions associated with Alzheimer's disease (AD) were investigated in transgenic mice overexpressing amyloid precusor protein (APP+) or transforming growth factor-beta1 (TGF+). Age-related impairments and their in vitro reversibility were evaluated, and underlying pathogenic mechanisms were assessed and compared with those seen in AD brains. Vasoconstrictions to 5-HT and endothelin-1 were preserved, except in the oldest (18-21 months of age) TGF+ mice. Despite unaltered relaxations to sodium nitroprusside, acetylcholine (ACh) and calcitonin gene-related peptide-mediated dilatations were impaired, and there was an age-related deficit in the basal availability of nitric oxide (NO) that progressed more gradually in TGF+ mice. The expression and progression of these deficits were unrelated to the onset or extent of thioflavin-S-positive vessels. Manganese superoxide dismutase (SOD2) was upregulated in pial vessels and around brain microvessels of APP+ mice, pointing to a role of superoxide in the dysfunctions elicited by amyloidosis. In contrast, vascular wall remodeling associated with decreased levels of endothelial NO synthase and cyclooxygenase-2 and increased contents of vascular endothelial growth factor and collagen-I and -IV characterized TGF+ mice. Exogenous SOD or catalase normalized ACh dilatations and NO availability in vessels from aged APP+ mice but had no effect in those of TGF+ mice. Increased perivascular oxidative stress was not evidenced in AD brains, but vascular wall alterations compared well with those seen in TGF+ mice. We conclude that brain vessel remodeling and associated alterations in levels of vasoactive signaling molecules are key contributors to AD cerebrovascular dysfunctions.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    OBJECTIVE: Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes...... by assessing expression of the receptor and pharmacological effects on collagen type II degradation under ex vivo and in vivo conditions. METHODS: Localization of the calcitonin receptor on articular chondrocytes was investigated by immunohistochemistry, and the expression by reverse transcriptase polymerase.......0001-1 microM]. In vivo, cartilage degradation was investigated in ovariectomized (OVX) rats administered with oral calcitonin [2 mg/kg calcitonin] for 9 weeks. RESULTS: The calcitonin receptor was identified in articular chondrocytes by immunohistochemistry and RT-PCR. Calcitonin concentration...

  9. Mechanisms behind Post-Thyroidectomy Hypocalcemia: Interplay of Calcitonin, Parathormone, and Albumin-A Prospective Study.

    Science.gov (United States)

    Chisthi, Meer M; Nair, Rakhi S; Kuttanchettiyar, Krishnakumar G; Yadev, Induprabha

    2017-08-01

    Hypocalcemia after thyroidectomy is attributed to injury or ischemia to parathyroid glands. Transient hypocalcemia in thyroidectomy when parathyroids are preserved is not adequately explained. Release of calcitonin and hypoalbuminemia are two proposed reasons. Primary objective of this study was to find the change in calcitonin in the postoperative period after total thyroidectomy. Secondarily, hypocalcemia and its correlation with calcitonin, albumin, and parathormone were also studied. This Cohort study was carried out at the general surgical department of a tertiary level teaching institution from April 2015 to December 2015. One hundred adult patients undergoing total thyroidectomy, with at least three parathyroids being preserved were included. Changes in calcium, calcitonin, albumin, and parathormone were studied based on preoperative levels and the values at 1, 6, 24, and 48 hr after surgery. Calcitonin increased at one hour after thyroidectomy and fell below preoperative levels subsequently. Parathormone showed a mild rise at one hour and normalized subsequently. Total calcium, corrected calcium, and albumin showed decline at one hour and recovered gradually over the next two days. At preoperative level, calcium had significant correlation with parathormone alone. Calcium levels at one hour had significant correlation with calcitonin. All post-operative calcium levels had significant correlation with parathormone and the number of parathyroids preserved in situ without auto-transplantation. There is significant hypocalcemia within the first 24 hr after thyroidectomy, caused by calcitonin release and hypoalbuminemia. Preservation of maximum number of parathyroids in-situ can counter and normalize this hypocalcemia.

  10. Levels of parathyroid hormone and calcitonin in serum among atomic bomb survivors

    International Nuclear Information System (INIS)

    Fujiwara, Saeko; Yokoyama, Naokata; Sasaki, Hideo; Kodama, Kazunori; Sposto, R.; Shimaoka, Katsutaro; Shiraki, Mastaka

    1994-01-01

    To examines the potential causes of increased levels of calcium in serum with increasing dose of atomic bomb radiation, which was obtained from the previous preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect of radiation on levels of calcium, PTH and calcitonin in serum was found, even after patients with hyperparathyroidism were excluded. The level of calcium in serum increased with radiation dose; this can be explained partly by the increase in the level of PTH with radiation dose. However, the dose effect on calcium remained even after adjustment for PTH, calcitonin and confounding factors such as renal function, serum albumin level and medication. Parathyroid hormone increased initially by 6.8% per gray, but the dose response leveled off after about 1 Gy. The level of calcitonin increased with radiation dose, probably in part due to feedback mechanisms stimulated by the increase in calcium. However, after adjustment for the level of calcium, the increase in the level of calcitonin with dose was still found. Although the etiological mechanisms of the effect of radiation on serum levels of calcium, PTH and calcitonin are unclear, radiation exposure may affect secretion of PTH and calcitonin and regulation of calcium a long time after atomic bomb exposure. 21 refs., 3 figs., 6 tabs

  11. Routine measurement of serum calcitonin in patients with nodular thyroid disorders?

    International Nuclear Information System (INIS)

    Dietlein, M.; Schmidt, M.; Schicha, H.; Wieler, H.; Schwab, R.; Goretzki, P.E.

    2008-01-01

    In spite of the fact that the German Society of Endocrinology has recommended calcitonin as screening-parameter the majority of physicians in Germany do not routinely use calcitonin in patients with thyroid nodules to exclude medullary thyroid cancer (MTC). The future revision of the recommendation should describe reference values for each commercially available assay, separately for men and women (basal and after pentagastrin-stimulation), and should define sonomorphological inclusion criteria. The epidemiological database of the prevalence of MTC is controversial and the specificity of basal elevated calcitonin levels is limited up to the 5-fold of the upper reference level. If renal insufficiency, bacterial infection, and an alcohol- or druginduced stimulation of calcitonin is excluded, hypercalcitoninaemia should be confirmed by a second measurement (if necessary using another assay). Stimulation of calcitonin by use of pentagastrin is mandatory prior to the decision on thyroidectomy. A stimulated calcitonin level < 100 pg/ml justifies 'wait and see'. If stimulated calcitonin levels range between 100 and 200 pg/ml or higher, the differentiation between C-cell hyperplasia and MTC remains uncertain, especially in men. The implementation of calcitonin- screening requires the definition of sonographic inclusion criteria and validation of each assay. Additional prerequisites are excellent logistic (short period between blood sampling and start of the laboratory test), knowledge of differential diagnoses, knowledge of the consumption of drugs and alcohol, availability of pentagastrin-testing and of moleculargenetic testing with full information to the patients and sufficient time before the decision on surgery is made. All this and the choice of a skilled surgeon, experienced in thyroidectomy and lymphadenectomy with a low rate of local complications are the rationale to recommend calcitonin-screening primarily in centers for thyroid disorders. (orig.)

  12. Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment.

    Science.gov (United States)

    Civitelli, R; Gonnelli, S; Zacchei, F; Bigazzi, S; Vattimo, A; Avioli, L V; Gennari, C

    1988-10-01

    To investigate the effectiveness of calcitonin treatment of postmenopausal osteoporosis in relation to bone turnover, we examined 53 postmenopausal osteoporotic women before and after one year of therapy with salmon calcitonin (sCT), at the dose of 50 IU every other day. Baseline evaluation revealed that 17 (32%) patients had high turnover (HTOP), and 36 (68%) normal turnover osteoporosis (NTOP) as assessed by measurement of whole body retention (WBR) of 99mTc-methylene diphosphonate. The two groups did not differ in terms of bone mineral content (BMC) measured by dual photon absorptiometry at both lumbar spine and femoral diaphysis. However, HTOP patients had higher levels of serum osteocalcin (OC) and urinary hydroxyproline excretion (HOP/Cr). Multivariate regression analysis showed no correlation between parameters of bone turnover (WBR, OC, HOP/Cr) and both femoral and vertebral bone density; the latter being negatively correlated only with the years elapsed since menopause (R2 = 0.406). Treatment with sCT resulted in a significant increase of vertebral BMC in the 53 patients taken as a whole group (+/- 7%, P less than 0.001). When the results obtained in HTOP and NTOP were analyzed separately, only those with HTOP showed a marked increment of spinal BMC (+22%, P less than 0.001), NTOP subjects neither gained nor lost bone mineral during the study. Femoral BMC decreased in the whole group after sCT therapy (-3%, P less than 0.003). However, HTOP patients maintained initial BMC values, whereas those with NTOP lost a significant amount of bone during the study period (-5%, P less than 0.001). The increase of vertebral bone mass was associated with a marked depression of bone turnover detectable in both subsets of patients and in the whole group. (a) assessment of bone turnover cannot help predict the severity of bone loss in postmenopausal osteoporosis; (b) calcitonin therapy appears to be particularly indicated for patients with high-turnover osteoporosis

  13. Radioimmunoasay of calcitonin in plasma and cerebro-spinal fluid

    International Nuclear Information System (INIS)

    Cecchettin, M.; Comberti, E.; Quinzanini, M.; Albertini, A.; Tarquini, B.

    1985-01-01

    An acceptable radioimmunoassay of calcitonin (CT) in man requires a highly purified antigen that can be labelled without loss of immunoreactivity. Radiolabelled synthetic CT showed an additional large peak of radiopeptides with high molecular weight. Therefore, a standard electrofocussing experiment was performed. Standards exhibiting an atypical behaviour after radioiodination showed a pI different from synthetic human monomer. CT electrophoretogram shows a larger component at pI 7.9 and two smaller contaminations at pI 8.6. Besides, the antisera available for CT assay are considered in healthy subjects. 0H 2 and COOH assays give non-homogeneous results. A CT assay in cerebrospinal fluid is performed. The direct assay was unable to detect significant correlation between serum and cerebrospinal levels both in physiological and pathological conditions. Finally, the quality control of the CT assay is discussed. (Auth./G.J.P.)

  14. Optimizing the radioimmunologic determination methods for cortisol and calcitonin

    International Nuclear Information System (INIS)

    Stalla, G.

    1981-01-01

    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) [de

  15. Calcitonin gene-related peptide receptor as a novel target for the management of people with episodic migraine: current evidence and safety profile of erenumab [Corrigendum

    Directory of Open Access Journals (Sweden)

    Giamberardino MA

    2018-01-01

    Full Text Available Giamberardino MA, Affaitati G, Costantini R, et al. J Pain Res. 2017;10:2751–2760.On page 2756, left column, lines 7 and 8: “Patients who previously had failed two preventative medications were excluded.” should have been: “Patients who previously had failed more than two preventive medications were excluded.”On page 2756, right column, lines 41–43: “There was a difference of −1.1 days in the main change in monthly migraine days between 70 mg erenumab group and placebo.” should have been: “There was a difference of −2.5 days in the mean change in monthly migraine  days between 70 mg erenumab group and placebo.”Read the original article  

  16. Effect of calcitonin gene-related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum

    DEFF Research Database (Denmark)

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

    2001-01-01

    increased by 154 +/- 15% in response to CGRP at 10(-8) mol L(-1). The release of gastrin was unaffected by pCGRP. In conclusion, pCGRP increases contractile activity in the porcine antrum, an effect that involves cholinergic mechanisms but is independent of the release of substance P and neurokinin A...

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

    Directory of Open Access Journals (Sweden)

    Rafael Loch Batista

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Robbins, Eric W; Travanty, Emily A; Yang, Kui; Iczkowski, Kenneth A

    2008-01-01

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

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

    International Nuclear Information System (INIS)

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

    1986-01-01

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

  20. Relative expression of genes related with cold tolerance in ...

    African Journals Online (AJOL)

    Low temperature is one of the main abiotic stresses affecting rice yield in Chile. Alterations in phenology and physiology of the crop are observed after a cold event. The objective of this work was to study the relative expression of genes related with cold stress in Chilean cultivars of rice. For this, we analyzed the expression ...

  1. Calcitonin effect on Achilles tendon healing. An experimental study on rabbits.

    Science.gov (United States)

    Petrou, C G; Karachalios, T S; Khaldi, L; Karantanas, A H; Lyritis, G P

    2009-01-01

    A positive potential effect of Calcitonin (CT) on Achilles tendon healing was investigated as well as the ability of MRI to follow the tendon healing process. A standardized tenotomy of the Achilles tendon was performed on forty-two rabbits. Twenty-one animals received daily 21 IU /kg Calcitonin intramuscularly (treatment group CT) during the experiment and the remaining received saline solution (control group P). Seven animals from each group were killed at one, two and three weeks postoperatively. All animals had serial MRI scans and tendon samples underwent biomechanical and histological testing. For both groups, animals of the same subgroup showed statistically significant difference in signal intensity values of MRI between the 1st and 3rd week (pTendon samples from group CT showed statistically significant difference in ultimate tensile strength compared to controls at 2 (ptendon healing stages. It is suggested that Calcitonin enhances Achilles tendon healing process.

  2. [Effects of the combined calcitonin and sodium etidronate therapy in Paget's disease of bone].

    Science.gov (United States)

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

    1982-03-03

    The therapy of Paget's bone disease is essentially based on the use of calcitonin and diphosphonates: both drugs, if used in large doses for long periods, have shown themselves able to provoke particular side-effects. It was, therefore, decided to study the therapeutic efficacy of combined low-dosage treatment using synthetic salmon calcitonin and sodium-etidronate on a group of patients with Paget's osteodystrophy. A clear evident diminution in plasma alkaline phosphatase, hydroxyprolinuria and whole body retention (WBR) of MDP-Tc99m was observed, demonstrating a reduction of metabolic turnover in the bone. No changes in the bone mass (BMC), evaluated by bone mineral detector, were observed at the end of treatment. With this treatment the plateau effect was shown to be appreciably less than normally occurs when either calcitonin or sodium etidronate are used alone.

  3. [Asu(1,7)E-CT, an analog of eel calcitonin. A comparative study in man with reference to other synthetic calcitonins].

    Science.gov (United States)

    Caniggia, A; Nuti, R; Vattimo, A; Galli, M; Turchetti, V; Franci, B; Martorelli, T; Righi, G

    1983-04-28

    (Asu) E-CT is a deaminodicarba-analog of the synthetic eel-calcitonin (E-CT) that shows specific activity and the potency reasonably high in comparison with that of the most potent natural hormone. The structure of its molecule indicates that the disulphide bond in calcitonins is not essential for the biological activity but only for the maintenance of the specific conformation by forming an intramolecular bridge. The instability of calcitonins should mainly be attributed to the presence of the disulfide bond and (Asu)E-CT proved to be more stable "in vitro" than native calcitonins. The more prolonged hypocalcemic effect of E-CT and its aminosuberic analog (Asu)E-CT has been accounted for to a greater stability of and persistence at the receptor site. (Asu) E-CT has been largely studied in Japan on experimental animals and successfully used in the treatment of hypercalcemia in man. On the contrary investigations on human administration of this analog are very scarce. The present paper reports studies carried out in normal subjects and Paget's disease patients to investigate the effects of (Asu)E-CT in man in comparison with the effects of synthetic human calcitonin (H-CT) and synthetic salmon calcitonin (S-CT). Two different experimental procedures have been used: 1) rapid intravenous injection of (Asu)E-CT (80 MRC. U.) or respectively of H-CT and S-CT (100 MRC. U.) in 15 subjects (7 normals and 8 with Paget's disease); 2) slow 7 days continuous subcutaneous infusion of similar daily amounts of (Asu)E-CT, H-CT and S-CT administered by a microjet pump device in 21 subjects (7 normals and 14 with Paget's disease). The intravenous administration of (Asu)E-CT induced a rapid and persistent decrease in total plasma calcium, ionized calcium and plasma phosphate that was more evident in Paget's disease patients than in normal subjects. No clearly cut differences have been observed with the hypocalcemic and hypophosphatemic effect of H-CT and S-CT administered

  4. Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

    Science.gov (United States)

    Kapetanakis, Emmanouil I; Antonopoulos, Athanassios S; Antoniou, Theofani A; Theodoraki, Kassiani A; Zarkalis, Dimitrios A; Sfirakis, Peter D; Chilidou, Despina A; Alivizatos, Peter A

    2005-05-01

    Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.

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

    Directory of Open Access Journals (Sweden)

    Pingping Chen-An

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

  6. [Synthetic human calcitonin in Paget's disease of bone and osteoporosis (author's transl)].

    Science.gov (United States)

    Nuti, R; Vattimo, A

    1981-01-30

    Synthetic human calcitonin was used in the treatment of 26 patients over a period of 1-14 months. 17 patients had Paget's disease of the bone, 6 postmenopausal osteoporosis and 3 Sudeck's syndrome. Subjective improvement (reduction of pain, improvement of mobility) was found in 15 patients with Paget's disease, in 4 females with postmenopausal osteoporosis and in all 3 patients with Sudeck's syndrome. Radiographic improvement of bone changes developed only very slowly. These results were confirmed by diminution of the exchangeable calcium pool indicating reduction of rates of osseous degradation. Calcitonin tolerance was acceptable. Transitory nausea and occasional vomiting occurred in 3 patients.

  7. Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor of the urinary bladder: case report

    Directory of Open Access Journals (Sweden)

    De Rosa Gaetano

    2005-07-01

    Full Text Available Abstract Background The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. Case presentation The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. Conclusion This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms.

  8. Possible Links among Mirror Neurons and Genes Related to Autism

    OpenAIRE

    MOCHIZUKI, Mai; 望月,麻衣

    2016-01-01

    Autism includes many neurodevelopmental disorders and defi cits in communication. Althoughresearchers have considered various origins, the onset mechanism is still not clear. The aim ofthis article is to provide some clues for interaction of autism with mirror neuronal and geneticfactors. First, the impact of neural brain cells considered to infl uence autism will be discussedwith reference to mirror neurons. Then, the discussion will move to genes related to autism.Consequently, it is argued...

  9. 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.)

  10. Radioimmunological determination of insulin, growth hormone and calcitonin in serum, ch. 2

    International Nuclear Information System (INIS)

    Froelich, M.

    1977-01-01

    Radioimmunoassay procedures for the determination of insulin, growth hormone and calcitonin in blood serum were developed. The procedure as well as the iodination of antigens and the generation of antibodies are described. Short-term and long-term quality control experiments dealing with specificity, recovery, sensitivity, intrassay variability and interassay variability are reported

  11. Specific binding of 125I-salmon calcitonin to rat brain

    International Nuclear Information System (INIS)

    Nakamuta, Hiromichi; Furukawa, Shinichi; Koida, Masao; Yajima, Haruaki; Orlowski, R.C.

    1981-01-01

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

  12. 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.

  13. Determination of calcitonin and the parathyroid hormone in blood serum for diagnosis of tumor metastases to the skeleton

    International Nuclear Information System (INIS)

    Smirnov, Yu.N.

    1986-01-01

    Calcitonin and parathyroid hormone were determined using a radioimmunoassay in the blood serum of lung, breast and kidney cancer patients who had undergone combined treatment for major disease, healthy males, patients with spinal tuberculosis and patients with eosinophilic granuloma of the cranial bones. A significant rise of the calsitonin level and change in the ratio of calcitonin and the parathyroid hormone were established in the blood serum of patients with tumor metastases to the skeleton, spinal tuberculosis and eosiniphilic cranial granuloma. During cancer patients monitoring the determination of calcitonin is recommended as a screening test for sceletal metastases to select patients for γ-topographic investigation

  14. Transcriptional regulation of genes related to progesterone production.

    Science.gov (United States)

    Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

    2015-01-01

    Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ(5)-Δ(4) isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production.

  15. Effect of antibodies to calcitonin on the pharmacokinetics and the pharmacodynamics of the hormone.

    Science.gov (United States)

    Tagliaro, F; Dorizzi, R; Luisetto, G

    1995-01-01

    Calcitonin pharmacokinetics and pharmacodynamics were studied in two groups of patients with postmenopausal osteoporosis, who, treated for one year with intranasal Asu1.7-eel calcitonin (eCT), had (Ab+) and had not (Ab-) developed a specific immune response to the drug. The treatment consisted of daily intranasal administrations of eCT (80 IU/die) with 1 g supplemental calcium. Eight women who had developed specific antibodies and 5 who had not, were given 50 IU of CT i.m., in order to assess the pharmacokinetics and pharmacodynamics of the drug. The rise of serum levels of the hormone was significantly greater in Ab+ than in Ab- patients. At the end of the study, no significant differences in mineral bone loss between the two groups were found. In conclusion, the presence of antibodies to eCT does not represent a negative event in the therapy of osteoporosis, but significantly affects the pharmacokinetics of the drug.

  16. Die Expression des Calcitonin receptor-like receptors in humanen Gliomen

    OpenAIRE

    Kappus, Christoph

    2014-01-01

    In dieser Arbeit wurden humane Gliome vom WHO-Grad II-IV auf das Vorkommen des Calcitonin receptor-like Rezeptors untersucht. Hierzu erfolgte zunächst der Nachweis der CRLR-RNS in den humanen Gliomzellinien G 109 und G 139, welche sich eindeutig posi-tiv zeigten. Sodann wurden paraffinasservierte Schnitte aus humanen Gliomen mittels im-munhistochemischer Färbung auf das Vorkommen des CRLRs untersucht. Hierzu diente ein Antikörper ...

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

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2013-08-01

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

  18. Calcitonin: Survey of new anatomy data to pathology and therapeutic aspects

    Directory of Open Access Journals (Sweden)

    Omar Faour

    2017-03-01

    Full Text Available Since the discovery of calcitonin (CT reports have questioned the physiological role of human CT in regulating calcemia. This peptide is produced out of the CT/CGRP gene splicing along with other factors or hormones, including somatostatin by synonymously called parafollicular cells, C thyrocytes or C cells located in the thyroid glands. The C cells have recently been proven to originate out of the ultimobranchial anlage of the pharyngeal endoderm instead of the neural crest cells as indicated in all textbooks. Both blood and urine CT and procalcitonin (proCT found in human and other mammals can also be secreted by cells located outside the thyroid glands. Taking account of dietetic calcium intake, CT assists in the homeostasis of bone mineral mass during growth, lactation, and pregnancy, hypo- and hyper gravity along with other paracrine thyroid secretions. Excess CT level in tissue fluids, needle aspirations and, now proCT, can diagnose sepsis, medullary thyroid or other carcinomas; caution to be taken with ectopic CT and gender-difference levels. Salmon CT as diurnal oral delivery seems, if proven not toxic, best suited to continue preventing or treating several defects, especially osteoporosis, orthopedic-related pains, perinatal or acute, fatal hypercalcemia. Contemplating old with recent physiological clinical results, human longitudinal morphologic and molecular data dealing with C cells and their paracrine interactions are few while only animal studies make us know much about CT. Human samples out of biopsies or cadavers should be further endeavored from development to aging to fully correlate normal with extreme or peculiar pathologies. Keywords: Calcitonin, Endoderm, Calcemia, Salmon calcitonin, Carcinoma, Osteoporosis, ECMO, Perinatal, Pro calcitonin

  19. VASCULAR SURGERY

    African Journals Online (AJOL)

    2016-06-02

    Jun 2, 2016 ... with the literature from South Africa over the last four decades, and reflects the high rate of interpersonal violence in the country.14,15 As expected, cervical ... via the intact circle of Willis in young patients is the most likely explanation for the lack of strokes. Five patients were referred to the Durban vascular ...

  20. Vascular Disorders

    Science.gov (United States)

    ... All Topics A-Z Videos Infographics Symptom Picker Anatomy Bones Joints Muscles Nerves Vessels Tendons About Hand Surgery What is a Hand Surgeon? What is a Hand Therapist? Media Find a Hand Surgeon Home Anatomy Vascular Disorders Email to a friend * required fields ...

  1. Experimental Study on the Effect of Calcitonin in Osteoporosis Induced by the Immobilization and Long-Term Glucocorticoid

    International Nuclear Information System (INIS)

    Park, Dong Jin; Lee, Sang Rae

    1989-01-01

    It is well known that the glucocorticoid induces osteoporosis by suppression of the osteoblast, but its effect on the osteoclast has some controversy whether it activates or suppresses the osteoclast. If the calcitonin, which is known to suppress the osteoclast, prevents the osteoporosis by glucocorticoid, then the suppression of the osteoclast by the glucocorticoid is not so significant. And if the calcitonin increases the osteoblastic activity, Tc-99m MDP uptake will be increased in spite of the glucocorticoid effect on the osteoblast. The immobilization operation was performed to the right leg of male Wistar rats weighing about 200 gm each. For 16 weeks after operation, rats were injected glucocorticoid alone or glucocorticoid and calcitonin. The bone density was measured by means of photodensitometry under reference aluminum step wedge and Tc-99m MDP uptake was available to the index of the osteoblastic activity. 1. The bone density of femoral head was markedly reduced than that of femoral shaft following ratio of cancellous and cortical components in both site. 2. glucocorticoid caused decrease in bone density of spine and femur, and there is significantly increase of it when medication of glucocorticoid and calcitonin injection simultaneously than that of glucocorticoid. 3. Tc-99m MDP uptake was revealed significant reduction in medication of glucocorticoid but increase in glucocorticoid and calcitonin injection simultaneously in later experimental period. 4. There was a slight reduction in plasma osteocalcin in medication of glucocorticoid through experimental periods and an increase in its value in case of giving glucocorticoid and calcitonin simultaneously in later experimental period. From these results, we suggest that osteoporosis by immobilization is more pronounced by glucocorticoid hormone and osteoporosis induced by immobilization and glucocorticoid use is prevented by calcitonin administration with increasing osteoblastic activity.

  2. Physiological studies in heterozygous calcium sensing receptor (CaSR gene-ablated mice confirm that the CaSR regulates calcitonin release in vivo

    Directory of Open Access Journals (Sweden)

    Kovacs Christopher S

    2004-04-01

    Full Text Available Abstract Background The calcium sensing receptor (CaSR regulates serum calcium by suppressing secretion of parathyroid hormone; it also regulates renal tubular calcium excretion. Inactivating mutations of CaSR raise serum calcium and reduce urine calcium excretion. Thyroid C-cells (which make calcitonin express CaSR and may, therefore, be regulated by it. Since calcium stimulates release of calcitonin, the higher blood calcium caused by inactivation of CaSR should increase serum calcitonin, unless CaSR mutations alter the responsiveness of calcitonin to calcium. To demonstrate regulatory effects of CaSR on calcitonin release, we studied calcitonin responsiveness to calcium in normal and CaSR heterozygous-ablated (Casr+/- mice. Casr+/- mice have hypercalcemia and hypocalciuria, and live normal life spans. Each mouse received either 500 μl of normal saline or one of two doses of elemental calcium (500 μmol/kg or 5 mmol/kg by intraperitoneal injection. Ionized calcium was measured at baseline and 10 minutes, and serum calcitonin was measured on the 10 minute sample. Results At baseline, Casr+/- mice had a higher blood calcium, and in response to the two doses of elemental calcium, had greater increments and peak levels of ionized calcium than their wild type littermates. Despite significantly higher ionized calcium levels, the calcitonin levels of Casr+/- mice were consistently lower than wild type at any ionized calcium level, indicating that the dose-response curve of calcitonin to increases in ionized calcium had been significantly blunted or shifted to the right in Casr+/- mice. Conclusions These results confirm that the CaSR is a physiological regulator of calcitonin; therefore, in response to increases in ionized calcium, the CaSR inhibits parathyroid hormone secretion and stimulates calcitonin secretion.

  3. Plasma levels of calcitonin in medullary thyroid carcinoma patients with and without the RET proto-oncogene mutations in exons 10 and 11

    Directory of Open Access Journals (Sweden)

    Samira Ehyayi

    2017-09-01

    Conclusion: Routine measurement of calcitonin has been investigated as a screening method for the diagnosis of medullary thyroid carcinoma patients. Nevertheless, additional data are required to definitely support routine measurement of calcitonin due to the role of RET proto-oncogene.

  4. Expression Profiling of Genes Related to Endothelial Cells Biology in Patients with Type 2 Diabetes and Patients with Prediabetes

    Directory of Open Access Journals (Sweden)

    Sara Moradipoor

    2016-01-01

    Full Text Available Endothelial dysfunction appears to be an early sign indicating vascular damage and predicts the progression of atherosclerosis and cardiovascular disorders. Extensive clinical and experimental evidence suggests that endothelial dysfunction occurs in Type 2 Diabetes Mellitus (T2DM and prediabetes patients. This study was carried out with an aim to appraise the expression levels in the peripheral blood of 84 genes related to endothelial cells biology in patients with diagnosed T2DM or prediabetes, trying to identify new genes whose expression might be changed under these pathological conditions. The study covered a total of 45 participants. The participants were divided into three groups: group 1, patients with T2DM; group 2, patients with prediabetes; group 3, control group. The gene expression analysis was performed using the Endothelial Cell Biology RT2 Profiler PCR Array. In the case of T2DM, 59 genes were found to be upregulated, and four genes were observed to be downregulated. In prediabetes patients, increased expression was observed for 49 genes, with two downregulated genes observed. Our results indicate that diabetic and prediabetic conditions change the expression levels of genes related to endothelial cells biology and, consequently, may increase the risk for occurrence of endothelial dysfunction.

  5. In vivo evaluation of an oral salmon calcitonin-delivery system based on a thiolated chitosan carrier matrix.

    Science.gov (United States)

    Guggi, Davide; Kast, Constantia E; Bernkop-Schnürch, Andreas

    2003-12-01

    To develop and evaluate an oral delivery system for salmon calcitonin. 2-Iminothiolane was covalently bound to chitosan in order to improve the mucoadhesive and cohesive properties of the polymer. The resulting chitosan-TBA conjugate (chitosan-4-thiobutylamidine conjugate) was homogenized with salmon calcitonin. mannitol, and a chitosan-Bowman-Birk inhibitor conjugate and a chitosan-elastatinal conjugate (6.75 + 0.25 + 1 + 1 + 1). Optionally 0.5% (m/m) reduced glutathione. used as permeation mediator, was added. Each mixture was compressed to 2 mg microtablets and enteric coated with a polymethacrylate. Biofeedback studies were performed in rats by oral administration of the delivery system and determination of the decrease in plasma calcium level as a function of time. Test formulations led to a significant (p thiolated chitosan, chitosan-enzyme-inhibitor conjugates and the permeation mediator glutathione seems to represent a promising strategy for the oral delivery of salmon calcitonin.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood...... hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered significantly 2 hours after administration of nasal SCT and throughout the first 24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis, urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11...

  8. Vascular ultrasound.

    Science.gov (United States)

    Pilcher, D B; Ricci, M A

    1998-04-01

    Surgeon-interpreted diagnostic ultrasound has become the preferred screening test and often the definitive test for the diagnosis of arterial stenosis, aneurysm, and venous thrombosis. As a modality for surveillance, its noninvasive quality makes it particularly appealing as the test of choice to screen patients for abdominal aortic aneurysms or to perform follow-up examinations on those patients with a carotid endartectomy or in situ bypass grafts. The increasing reliance on intraoperative duplex imaging of vascular procedures demands that the surgeon learn the skills to perform the studies without a technologist or radiologist to interpret the examination.

  9. Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74.

    Science.gov (United States)

    Miller, Philip S; Barwell, James; Poyner, David R; Wigglesworth, Mark J; Garland, Stephen L; Donnelly, Dan

    2010-01-01

    The receptor for calcitonin gene-related peptide (CGRP) has been the target for the development of novel small molecule antagonists for the treatment of migraine. Two such antagonists, BIBN4096BS and MK-0974, have shown great promise in clinical trials and hence a deeper understanding of the mechanism of their interaction with the receptor is now required. The structure of the CGRP receptor is unusual since it is comprised of a hetero-oligomeric complex between the calcitonin receptor-like receptor (CRL) and an accessory protein (RAMP1). Both the CLR and RAMP1 components have extracellular domains which interact with each other and together form part of the peptide-binding site. It seems likely that the antagonist binding site will also be located on the extracellular domains and indeed Trp-74 of RAMP1 has been shown to form part of the binding site for BIBN4096BS. However, despite a chimeric study demonstrating the role of the N-terminal domain of CLR in antagonist binding, no specific residues have been identified. Here we carry out a mutagenic screen of the extreme N-terminal domain of CLR (residues 23-63) and identify a mutant, Met-42-Ala, which displays 48-fold lower affinity for BIBN4096BS and almost 900-fold lower affinity for MK-0974. In addition, we confirm that the Trp-74-Lys mutation at human RAMP1 reduces BIBN4096BS affinity by over 300-fold and show for the first time a similar effect for MK-0974 affinity. The data suggest that the non-peptide antagonists occupy a binding site close to the interface of the N-terminal domains of CLR and RAMP1. Copyright 2009 Elsevier Inc. All rights reserved.

  10. 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

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

    Science.gov (United States)

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

    1975-01-01

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

  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...

  13. A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6-month study.

    Science.gov (United States)

    Kung, A W C; Pasion, E G; Sofiyan, M; Lau, E M C; Tay, B K; Lam, K S; Wilawan, K; Ongphiphadhanakul, B; Thiebaud, D

    2006-05-01

    The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis. A total of 104 patients (n = 47 teriparatide [20 g/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (> or = 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study. Teriparatide was associated with a 5.03 +/- 4.77% increase in lumbar spine BMD (p < 0.0001, mean +/- SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 +/- 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters. Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar

  14. Buccal transmucosal delivery of calcitonin in rabbits using thin-film composites.

    Science.gov (United States)

    Cui, Zhengrong; Mumper, Russell J

    2002-12-01

    Salmon Calcitonin (sCT) is used to treat hypercalcemia resulting from Paget's disease and osteoporosis. sCT is available either in a sterile injectable form or nasal spray. Alternative and more cost-effective dosage forms for the delivery of calcitonin are needed. We sought to deliver sCT transmucosally using a previously reported mucoadhesive bilayer thin-film composite (TFC) via the buccal route. Forty micrograms of salmon calcitonin (200-IU) was loaded on preformed TFCs. In vitro release of sCT from TFCs was monitored in phosphate-buffered saline (10 mM, pH 7.4) at 37degrees C. Female New Zealand White rabbits (n = 6) were dosed with 40 microg of sCT either by injection via the ear vein or by applying sCT-loaded TFCs directly on the buccal pouch. Blood was collected at various times, and the plasma sCT and calcium concentrations were quantified. WinNonlin was used to determine the relevant pharmacokinetic parameters. In vitro, over 80% of sCT was released from the TFCs within 240 min. Super Case-II transport was indicated as the primary release mechanism. Rabbits injected intravenously had C(max), Cls, Vss, and AUC(0-inf) values of 75.1 +/- 6.5 ng/mL, 20.7 +/- 3.3 mL/min, 637 +/- 141 mL, and 1925 +/- 237 ng*min/mL, respectively. Rabbits dosed via the buccal route had C(max) Cls, and AUC(0-400 min values of 4.6 +/- 1.6 ng/mL, 22.0 +/- 5.9 mL/min, and 842.9 +/- 209.7 ng*min/mL, respectively. The relative bioavailability for rabbits treated with the TFCs was 43.8 +/- 10.9% with a CV of 24.9%. The reductions in plasma calcium levels after administration of sCT by both the intravenous and buccal route were comparable. The TFCs effectively delivered therapeutically efficacious amounts of sCT across the buccal mucosa in rabbits.

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

    International Nuclear Information System (INIS)

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

    1981-01-01

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

  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

    hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate...... to be optimal, as elongating the chain causes greater binding to the cell membrane but similar permeability, and we speculate that increasing the chain length further may decrease the permeability. In conclusion, acylated sCT acts as its own in vitro intestinal permeation enhancer, with reversible effects...... on Caco-2 cells, indicating that acylation of sCT may represent a promising tool to increase intestinal permeability without adding oral permeation enhancers....

  17. Gel chromatography of immunoextracted plasma calcitonin in response to the calcium clamp in healthy males

    International Nuclear Information System (INIS)

    Bucht, E.; Toerring, O.; Sjoeberg, H.E.

    1985-01-01

    A radioimmunoassay (RIA) was developed for immunoreactive calcitonin (iCT) in human plasma. Antibodies against synthetic human calcitonin (hCT) coupled to bovine serum albumin (BSA) were raised in rabbits and were directed against the carboxy terminal part of CT. The detection limit of the assay was 8 pg/ml. In 7 males the iCT response to a calcium-clamp was studied. Blood was collected at 0,30 and 60 min after the start of the calcium infusion. iCT was measured directly in plasma and in extracts obtained after purification of plasma iCT by means of immobilized CT antiboides. There was a good correlation between iCT in plasma samples and extracts, r = 0.993, n = 14 (P< 0.001). Dilution curves of extracts and plasma were parallel with the hCT standard curves. Gel chromatography of the extracts on Sephadex G-50 and G-75 disclosed heterogeneity of iCT in normal plasma during basal conditions as well as during calcium stimulation. Thirty min after the start of the calcium clamp all molecular forms, most likely constituting monomeric and dimeric CT and larger forms, were increased, while after 60 min iCT seemed to constitute predominantly forms larger than monomeric TCY. Basal levels of unextracted iCT in healthy males (n = 44, 37 +/- 10 years) were 15 +/- 9 pg-equivalents/ml (mean +/- SD), which was higher than in females (n = 40, 32 +/- 9 years) 11 +/- 4 pg-equivalents/ml (P < 0.05). (author)

  18. Vasopressin Gene-Related Products in the Management of Breast Cancer

    National Research Council Canada - National Science Library

    North, William

    1999-01-01

    ...), and this information coupled with an absence of vasopressin gene-related products from fibrocystic disease potentially provides us with a new screening test for distinguishing both breast cancer...

  19. Vasopressin Gene-Related Products in the Management of Breast Cancer

    National Research Council Canada - National Science Library

    North, William

    1998-01-01

    .... The VP gene is expressed by seemingly all breast cancers and by all DCIS, and this information coupled with an absence of VP gene-related products from fibrocystic disease potentially provides us...

  20. 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

  1. Calcitonin causes a sustained inhibition of protein kinase C-stimulated bone resorption in contrast to the transient inhibition of parathyroid hormone-induced bone resorption

    International Nuclear Information System (INIS)

    Ransjoe, M.; Lerner, U.H.

    1990-01-01

    Calcitonin is a well known inhibitor of osteoclastic bone resortion, both in vivo and in vitro. However, it is also known that calcitonin has only a transient inhibitory effect on bone resorption. The mechanism for this so-called ''escape from inhibition'' phenomenon is not clear. In the present study, the inhibitory effect of calcitonin on phorbol ester-induced bone resorption was examined in cultured neonatal mouse calvaria. Bone resorption was assessed as the release of radioactivity from bones prelabelled in vivo with 45 Ca. Two proteon kinase C-activating phorbol esters, phorbol-12-myristate-13-acetate and phorbol-12,13-dibutyrate, both stimulated 45 Ca release in 120-h cultures at a concentration of 10 nmul/l. Calcitonin (30 nmol/l) inhibited phorbol esterstimulated bone resorption without any ''escape from inhibition''. This was in contrast to the transient inhibitory effect of calcitonin on bone resorption stimulated by parathyroid hormone (10 nmol/l), prostaglandin E 2 (2 μmol/l), and bradykinin (1 μmol/l). Our results suggest that activation of protein kinase C produces a sustained inhibitory effect of calcitonin on bone resorption. (author)

  2. Bioprinting for vascular and vascularized tissue biofabrication.

    Science.gov (United States)

    Datta, Pallab; Ayan, Bugra; Ozbolat, Ibrahim T

    2017-03-15

    Bioprinting is a promising technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision. Bioprinting enables the deposition of various biologics including growth factors, cells, genes, neo-tissues and extra-cellular matrix-like hydrogels. Benefits of bioprinting have started to make a mark in the fields of tissue engineering, regenerative medicine and pharmaceutics. Specifically, in the field of tissue engineering, the creation of vascularized tissue constructs has remained a principal challenge till date. However, given the myriad advantages over other biofabrication methods, it becomes organic to expect that bioprinting can provide a viable solution for the vascularization problem, and facilitate the clinical translation of tissue engineered constructs. This article provides a comprehensive account of bioprinting of vascular and vascularized tissue constructs. The review is structured as introducing the scope of bioprinting in tissue engineering applications, key vascular anatomical features and then a thorough coverage of 3D bioprinting using extrusion-, droplet- and laser-based bioprinting for fabrication of vascular tissue constructs. The review then provides the reader with the use of bioprinting for obtaining thick vascularized tissues using sacrificial bioink materials. Current challenges are discussed, a comparative evaluation of different bioprinting modalities is presented and future prospects are provided to the reader. Biofabrication of living tissues and organs at the clinically-relevant volumes vitally depends on the integration of vascular network. Despite the great progress in traditional biofabrication approaches, building perfusable hierarchical vascular network is a major challenge. Bioprinting is an emerging technology to fabricate design-specific tissue constructs due to its ability to create complex, heterocellular structures with anatomical precision

  3. Indirect [3H]methyl exchange as a general method for labeling methionine residues: application to calcitonin.

    Science.gov (United States)

    Barling, P M; Preston, J R; Bibby, N J; Wilson, T

    1985-02-01

    Native porcine calcitonin from Armour is known to contain two components. It is shown that these can be separated by cation-exchange chromatography in 8 M urea. The technique of [3H]methyl exchange on the methionine residue was used to prepare each of these in a tritiated form. The reduced components formed by demethylation were found to readily reoxidize at neutral pH, to regenerate the disulfide bridge. Evidence is provided to show that the two forms were partially interconverted during these steps. The reoxidized 3H-labeled products were found to be indistinguishable in chemical, immunological, and biological properties from the equivalent components in native porcine calcitonin and had specific activities of approximately 20 Ci/mmol. It is concluded that this labeling method can be conveniently applied to peptides containing one or more disulfide bridges, to give products of high specific activity in acceptable yield, provided appropriate conditions are used to ensure correct reoxidation occurs.

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

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2002-06-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Hendriks, J Th.A.M. [Department of Internal Medicine, St. Franciscus Hospital, 4708 AE Roosendaal, The Netherlands; Smeenk, D [Department of Endocrinology, University Hospital, 2333 AA Leiden, The Netherlands

    1979-01-01

    Seventeen normocalcaemic patients with severe hyperthyroidism were examined before therapy was initiated; 9 were re-examined about 1 year later. Studies with /sup 47/Ca 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 PO/sub 4/, it was found that during fasting the plasma PO/sub 4/ 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 PO/sub 4/ 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.

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

    International Nuclear Information System (INIS)

    Hendriks, J.Th.A.M.; Smeenk, D.

    1979-01-01

    Seventeen normocalcaemic patients with severe hyperthyroidism were examined before therapy was initiated; 9 were re-examined about 1 year later. Studies with 47 Ca 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 PO 4 , it was found that during fasting the plasma PO 4 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 PO 4 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)

  7. Relationship of calcitonin mRNA expression to the differentiation state of HL 60 cells.

    Science.gov (United States)

    Kiefer, P; Bacher, M; Pflüger, K H

    1994-05-01

    Raised plasma levels of immunoreactive human calcitonin (ihCT) can be found in patients with myeloid leukemia and seem to indicate a poor prognosis. High levels were found in acute undifferentiated and acute myeloblastic leukemia. To test whether CT expression could be a marker of myeloid differentiation, we used the promyelocytic leukemia cell line HL 60 which also expresses ihCT as a model system for myeloid differentiation. Exponentially growing HL 60 cells as well as differentiation induced HL 60 cells expressed a single 1.0 Kb CT transcript. The induction of HL 60 cell differentiation along the granulocytic lineage by DMSO or HMBA had no effect on the level of CT transcripts. Induction of monocytic/macrophagic differentiation by TPA resulted in a transient, about 10-fold elevated expression of CT steady state mRNA after 24 h. In contrast to TPA, induction of HL 60 cell differentiation along the monocytic pathway by Vit D3 had no detectable effect on the level of the CT in RNA expression at corresponding time points. These findings suggest that the transient induction of CT steady state mRNA expression by TPA is rather a direct effect of the phorbol ester than commitment along the monocytic line of differentiation.

  8. Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation

    Science.gov (United States)

    Davis, Reema B.; Kechele, Daniel O.; Blakeney, Elizabeth S.; Pawlak, John B.

    2017-01-01

    Lymphatics play a critical role in maintaining gastrointestinal homeostasis and in the absorption of dietary lipids, yet their roles in intestinal inflammation remain elusive. Given the increasing prevalence of inflammatory bowel disease, we investigated whether lymphatic vessels contribute to, or may be causative of, disease progression. We generated a mouse model with temporal and spatial deletion of the key lymphangiogenic receptor for the adrenomedullin peptide, calcitonin receptor–like receptor (Calcrl), and found that the loss of lymphatic Calcrl was sufficient to induce intestinal lymphangiectasia, characterized by dilated lacteals and protein-losing enteropathy. Upon indomethacin challenge, Calcrlfl/fl/Prox1-CreERT2 mice demonstrated persistent inflammation and failure to recover and thrive. The epithelium and crypts of Calcrlfl/fl/Prox1-CreERT2 mice exhibited exacerbated hallmarks of disease progression, and the lacteals demonstrated an inability to absorb lipids. Furthermore, we identified Calcrl/adrenomedullin signaling as an essential upstream regulator of the Notch pathway, previously shown to be critical for intestinal lacteal maintenance and junctional integrity. In conclusion, lymphatic insufficiency and lymphangiectasia caused by loss of lymphatic Calcrl exacerbates intestinal recovery following mucosal injury and underscores the importance of lymphatic function in promoting recovery from intestinal inflammation. PMID:28352669

  9. Genetic polymorphisms in calcitonin receptor gene and risk for recurrent kidney calcium stone disease.

    Science.gov (United States)

    Shakhssalim, Nasser; Basiri, Abbas; Houshmand, Massoud; Pakmanesh, Hamid; Golestan, Banafsheh; Azadvari, Mohaddeseh; Aryan, Hajar; Kashi, Amir H

    2014-01-01

    In this study the full sequence of the calcitonin receptor gene (CALCR) in a group of Iranian males suffering from recurrent calcium urinary stones was compared with that of a control group. Serum and urinary biochemistry related to urolithiasis were evaluated in 105 males diagnosed with recurrent kidney calcium stones and 101 age-matched healthy control males. The polymerase chain reaction single-strand conformation polymorphism method was used to detect new polymorphisms in the CALCR. Nine polymorphisms were detected; seven were in the non-coding and two in the coding region. The T allele associated with the 3'UTR+18C>T polymorphism was observed exclusively in the stone formers. The exact odds ratio for the T allele in this locus for those at risk of stone formation was 36.72 (95% CI 4.95-272.0) (p C and IVS1insA polymorphisms in intron 1 were associated with kidney stone disease (p T and intron 1 polymorphisms in the CALCR and the risk of kidney stone disease. 2013 S. Karger AG, Basel.

  10. Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

    Science.gov (United States)

    Pina, Géraldine; Dubois, Séverine; Murat, Arnaud; Berger, Nicole; Niccoli, Patricia; Peix, Jean-Louis; Cohen, Régis; Guillausseau, Claudine; Charrie, Anne; Chabre, Olivier; Cornu, Catherine; Borson-Chazot, Françoise; Rohmer, Vincent

    2013-03-01

    To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. Multicentric prospective study. A total of 162 patients with basal CT basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P basal CT instead of the previously used 10-ng/l threshold. The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test. © 2012 Blackwell Publishing Ltd.

  11. Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs.

    Science.gov (United States)

    Nakamura, H; Asano, T; Haruta, K; Takeda, K

    1995-01-01

    Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.

  12. Effects of calcitonin on orthodontic tooth movement and associated root resorption in rats.

    Science.gov (United States)

    Guan, Ling; Lin, Suai; Yan, Weijun; Chen, Lei; Wang, Xiaofeng

    2017-11-01

    Our main aim was to evaluate the effects of calcitonin (CT) on orthodontic tooth movement (OTM) and orthodontic root resorption in a rat model. Eighty male Wistar rats were randomly divided into five groups. Rats in the negative control group were not given any appliances or injections. All the remaining rats were used to establish a model of OTM. The positive control group were then injected with normal saline, while rats in the three experimental groups were injected with 0.2 IU, 1 IU or 5 IU/kg/day CT. Nickel-titanium closed-coil springs were used to deliver an initial 50 g mesial force to the left maxillary first molar for 14 days in rats in the positive control group and the experimental groups. Each group was randomly subdivided into two groups, one for analysis of tooth movement, tissue changes and tartrate-resistant acid phosphatase (TRAP)-positive cells in alveolar bone, the other to examine root resorption by scanning electron microscopy. The OTM distance, the number of force-induced osteoclasts and root resorption areas were significantly decreased in CT-injected rats in a dose-dependent manner. Administration of CT reduces the root resorption area and may therefore be effective as a novel adjunctive orthodontic approach to diminish undesired tooth movement via enhancing anchorage or preventing relapse after OTM.

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

    Science.gov (United States)

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

    2002-01-01

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

  14. Calcitonin Receptor Signaling Inhibits Muscle Stem Cells from Escaping the Quiescent State and the Niche

    Directory of Open Access Journals (Sweden)

    Masahiko Yamaguchi

    2015-10-01

    Full Text Available Calcitonin receptor (Calcr is expressed in adult muscle stem cells (muscle satellite cells [MuSCs]. To elucidate the role of Calcr, we conditionally depleted Calcr from adult MuSCs and found that impaired regeneration after muscle injury correlated with the decreased number of MuSCs in Calcr-conditional knockout (cKO mice. Calcr signaling maintained MuSC dormancy via the cAMP-PKA pathway but had no impact on myogenic differentiation of MuSCs in an undifferentiated state. The abnormal quiescent state in Calcr-cKO mice resulted in a reduction of the MuSC pool by apoptosis. Furthermore, MuSCs were found outside their niche in Calcr-cKO mice, demonstrating cell relocation. This emergence from the sublaminar niche was prevented by the Calcr-cAMP-PKA and Calcr-cAMP-Epac pathways downstream of Calcr. Altogether, the findings demonstrated that Calcr exerts its effect specifically by keeping MuSCs in a quiescent state and in their location, maintaining the MuSC pool.

  15. Upregulation of genes related to bone formation by γ-amino butyric acid and γ-oryzanol in germinated brown rice is via the activation of GABAB-receptors and reduction of serum IL-6 in rats.

    Science.gov (United States)

    Muhammad, Sani Ismaila; Maznah, Ismail; Mahmud, Rozi; Zuki, Abu Bakar Zakaria; Imam, Mustapha Umar

    2013-01-01

    Osteoporosis and other bone degenerative diseases are among the most challenging non-communicable diseases to treat. Previous works relate bone loss due to osteoporosis with oxidative stress generated by free radicals and inflammatory cytokines. Alternative therapy to hormone replacement has been an area of interest to researchers for almost three decades due to hormone therapy-associated side effects. In this study, we investigated the effects of gamma-amino butyric acid (GABA), gamma-oryzanol (ORZ), acylated steryl glucosides (ASG), and phenolic extracts from germinated brown rice (GBR) on the expression of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2), secreted protein acidic and rich in cysteine (SPARC), runt-related transcription factor 2 (RUNX-2), osteoblast-specific transcription factor osterix (Osx), periostin, osteoblast specific factor (Postn), collagen 1&2 (Col1&2), calcitonin receptor gene (CGRP); body weight measurement and also serum interleukin-6 (IL-6) and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and ASG at (100 and 200 mg/kg); estrogen (0.2 mg/kg), or remifemin (10 and 20 mg/kg), compared to ovariectomized non-treated group as well as non-ovariectomized non-treated (sham) group. Enzyme-linked immunosorbent assay was used to measure the IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the bone tissue was determined using the Genetic Analysis System (Beckman Coulter Inc., Brea, CA, USA). The results indicate that groups treated with GABA (100 and 200 mg/kg) showed significant upregulation of SPARC, calcitonin receptor, and BMP-2 genes (P < 0.05), while the ORZ-treated group (100 and 200 mg/kg) revealed significant (P < 0.05) upregulation of Osx, Postn, RUNX-2, and Col1&2. Similarly, IL-6 concentration decreased, while osteocalcin levels increased significantly (P < 0.05) in the treated groups as compared to ovariectomized non-treated groups. GABA and ORZ from

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

    DEFF Research Database (Denmark)

    Hasselgren, Martin; Hegedüs, Laszlo; Godballe, Christian

    2009-01-01

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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    Highlights: • Molecular imprinting-based sensor for medullary thyroid carcinoma marker was developed. • ZnO nanostructure was used as a platform for synthesis of imprinted polymer. • Imprinted polymer was prepared by ARGET–ATRP method. • A novel and biocompatible tyrosine amino acid derivative was used as monomer. • Linear working range is found from 9.99 ng L −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)

  18. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

    Directory of Open Access Journals (Sweden)

    Baoman Wang

    2015-01-01

    Full Text Available Apoptosis is the process of programmed cell death (PCD that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature.

  19. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  20. Vascular grading of angiogenesis

    DEFF Research Database (Denmark)

    Hansen, S; Grabau, D A; Sørensen, Flemming Brandt

    2000-01-01

    The study aimed to evaluate the prognostic value of angiogenesis by vascular grading of primary breast tumours, and to evaluate the prognostic impact of adding the vascular grade to the Nottingham Prognostic Index (NPI). The investigation included 836 patients. The median follow-up time was 11...... years and 4 months. The microvessels were immunohistochemically stained by antibodies against CD34. Angiogenesis was graded semiquantitatively by subjective scoring into three groups according to the expected number of microvessels in the most vascular tumour area. The vascular grading between observers...... impact for 24% of the patients, who had a shift in prognostic group, as compared to NPI, and implied a better prognostic dissemination. We concluded that the angiogenesis determined by vascular grading has independent prognostic value of clinical relevance for patients with breast cancer....

  1. Is calcitonin an active hormone in the onset and prevention of hypocalcemia in dairy cattle?

    Science.gov (United States)

    Rodríguez, E M; Bach, A; Devant, M; Aris, A

    2016-04-01

    The objective of this study was to assess the potential importance of calcitonin (CALC) in the onset of subclinical hypocalcemia (experiment 1) and in the physiological mechanisms underlying the prevention of bovine hypocalcemia under metabolic acidosis (experiments 2 and 3). In experiment 1, 15 Holstein cows naturally incurring subclinical hypocalcemia during the first 5d postpartum were classified as low subclinical hypocalcemia (LSH) when blood Ca concentrations were between 7.5 and 8.5mg/dL, or as high subclinical hypocalcemia (HSH) when blood Ca concentrations were between 6.0 and 7.6 mg/dL. Blood samples were taken daily from d -5 to 5 relative to parturition to determine concentrations of parathyroid hormone (PTH), CALC, and 1,25(OH)2D3. In experiment 2, 24 Holstein bulls (497 ± 69 kg of body weight and 342 ± 10.5d of age) were assigned to 2 treatments (metabolic acidosis or control). Metabolic acidosis was induced by an oral administration of ammonium chloride (2.5 mEq/d) during 10 d, and animals were slaughtered thereafter. Blood samples were collected before slaughter to determine CALC, PTH, 1,25(OH)2D3, and samples of urine, kidney, parathyroid, and thyroid glands were obtained immediately after slaughter to determine expression of several genes in these tissues. Last, in experiment 3, we tested the activity of CALC under metabolic acidosis in vitro using breast cancer cell (T47D) cultures. Although PTH tended to be greater in HSH than in LSH, the levels of 1,25(OH)2D3 were lower in HSH cows (experiment 1). Blood CALC concentration was not affected by the severity of subclinical hypocalcemia, but it was influenced by days from calving (experiment 1). The expression of PTH receptor (PTHR) in the kidney was increased under metabolic acidosis (experiment 2). Furthermore, the activity of CALC was impaired under acidic blood pH (experiment 3). In conclusion, the CALC rise in HSH cows after calving impaired the recovery of blood Ca concentrations because the

  2. No Evidence of Increase in Calcitonin Concentrations or Development of C-Cell Malignancy in Response to Liraglutide for Up to 5 Years in the LEADER Trial

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Sherman, Steven I; Tuttle, R Michael

    2018-01-01

    of increase in calcitonin concentrations in male (estimated treatment ratio [ETR] 1.03 [95% CI 1.00, 1.06]; P = 0.068) and female (ETR 1.00 [95% CI 0.97, 1.02]; P = 0.671) subgroups. There were no episodes of C-cell hyperplasia or medullary thyroid carcinoma in liraglutide-treated patients. CONCLUSIONS...

  3. Early effects of synthetic bovine parathyroid hormone and synthetic salmon calcitonin on urinary excretion of cyclic AMP, phosphate and calcium in man.

    Science.gov (United States)

    Caniggia, A; Gennari, C; Vattimo, A; Nardi, P; Nuti, R; Galli, M

    1976-04-20

    Bovine synthetic parathyroid hormone infused intravenously in man increased both the urinary excretion of cyclic AMP and the urinary excretion of phosphate whereas a Salmon synthetic calcitonin infusion increased the urinary excretion of phosphate without change in urinary excretion of cyclic AMP. These data are consistent with the hypothesis that different renal mechanisms are involved in the response to each hormone.

  4. 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...

  5. Vascular Access in Children

    International Nuclear Information System (INIS)

    Krishnamurthy, Ganesh; Keller, Marc S.

    2011-01-01

    Establishment of stable vascular access is one of the essential and most challenging procedures in a pediatric hospital. Many clinical specialties provide vascular service in a pediatric hospital. At the top of the “expert procedural pyramid” is the pediatric interventional radiologist, who is best suited and trained to deliver this service. Growing awareness regarding the safety and high success rate of vascular access using image guidance has led to increased demand from clinicians to provide around-the-clock vascular access service by pediatric interventional radiologists. Hence, the success of a vascular access program, with the pediatric interventional radiologist as the key provider, is challenging, and a coordinated multidisciplinary team effort is essential for success. However, there are few dedicated pediatric interventional radiologists across the globe, and also only a couple of training programs exist for pediatric interventions. This article gives an overview of the technical aspects of pediatric vascular access and provides useful tips for obtaining vascular access in children safely and successfully using image guidance.

  6. Pediatric vascular access

    International Nuclear Information System (INIS)

    Donaldson, James S.

    2006-01-01

    Pediatric interventional radiologists are ideally suited to provide vascular access services to children because of inherent safety advantages and higher success from using image-guided techniques. The performance of vascular access procedures has become routine at many adult interventional radiology practices, but this service is not as widely developed at pediatric institutions. Although interventional radiologists at some children's hospitals offer full-service vascular access, there is little or none at others. Developing and maintaining a pediatric vascular access service is a challenge. Interventionalists skilled in performing such procedures are limited at pediatric institutions, and institutional support from clerical staff, nursing staff, and technologists might not be sufficiently available to fulfill the needs of such a service. There must also be a strong commitment by all members of the team to support such a demanding service. There is a slippery slope of expected services that becomes steeper and steeper as the vascular access service grows. This review is intended primarily as general education for pediatric radiologists learning vascular access techniques. Additionally, the pediatric or adult interventional radiologist seeking to expand services might find helpful tips. The article also provides education for the diagnostic radiologist who routinely interprets radiographs containing vascular access devices. (orig.)

  7. Vascular malformations in pediatrics

    International Nuclear Information System (INIS)

    Reith, W.; Shamdeen, M.G.

    2003-01-01

    Vascular malformations are the cause of nearly all non-traumatic intracranial hemorrhage in children beyond the neonatal stage. Therefore, any child presenting with spontaneous intracranial hemorrhage should be evaluated for child abuse and for vascular malformations. Intracerebral malformations of the cerebral vasculature include vein of Galen malformations, arteriovenous malformation (AVM), cavernomas, dural arteriovenous fistulas, venous anomalies (DVA), and capillary teleangiectasies. Although a few familial vascular malformation have been reported, the majority are sporadic. Clinical symptoms, diagnostic and therapeutic options are discussed. (orig.) [de

  8. SACS gene-related autosomal recessive spastic ataxia of Charlevoix-Saguenay from South India

    Directory of Open Access Journals (Sweden)

    M Suraj Menon

    2016-01-01

    Full Text Available Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS is a neurodegenerative disorder characterized by late infantile onset spastic ataxia and other neurological features. Initially described in the Charlevoix-Saguenay region of Quebec, Canada, it is being increasingly reported from many other countries. Here, we present the case of a 20-year-old male from South India, who presented with progressive ataxia, spasticity, and peripheral neuropathy with imaging features and genetic testing suggestive of SACS gene-related ARSACS. The phenotypic variability from other cases and occurrence in a geographically distinct region is stressed upon to alert the clinicians to consider ARSACS in progressive ataxias.

  9. Uterine Vascular Lesions

    Science.gov (United States)

    Vijayakumar, Abhishek; Srinivas, Amruthashree; Chandrashekar, Babitha Moogali; Vijayakumar, Avinash

    2013-01-01

    Vascular lesions of the uterus are rare; most reported in the literature are arteriovenous malformations (AVMs). Uterine AVMs can be congenital or acquired. In recent years, there has been an increasing number of reports of acquired vascular lesions of the uterus following pregnancy, abortion, cesarean delivery, and curettage. It can be seen from these reports that there is confusion concerning the terminology of uterine vascular lesions. There is also a lack of diagnostic criteria and management guidelines, which has led to an increased number of unnecessary invasive procedures (eg, angiography, uterine artery embolization, hysterectomy for abnormal vaginal bleeding). This article familiarizes readers with various vascular lesions of the uterus and their management. PMID:24340126

  10. Magnetic resonance vascular imaging

    International Nuclear Information System (INIS)

    Axel, L

    1989-01-01

    The basis principles of MRI are reviewed in order to understand how blood flow effects arise in conventional imaging. Then some of the ways these effects have ben used in MRI techniques specifically designed for vascular imaging, are considered. (author)

  11. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean) Cattle.

    Science.gov (United States)

    Lim, Dajeong; Lee, Seung-Hwan; Kim, Nam-Kuk; Cho, Yong-Min; Chai, Han-Ha; Seong, Hwan-Hoo; Kim, Heebal

    2013-01-01

    Marbling (intramuscular fat) is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the 'marbling score' trait and systemically analyzed the network topology in Hanwoo (Korean cattle). As a result, we determined 3 modules (gene groups) that showed statistically significant results for marbling score. In particular, one module (denoted as red) has a statistically significant result for marbling score (p = 0.008) and intramuscular fat (p = 0.02) and water capacity (p = 0.006). From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA) have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  12. Gene Co-expression Analysis to Characterize Genes Related to Marbling Trait in Hanwoo (Korean Cattle

    Directory of Open Access Journals (Sweden)

    Dajeong Lim

    2013-01-01

    Full Text Available Marbling (intramuscular fat is an important trait that affects meat quality and is a casual factor determining the price of beef in the Korean beef market. It is a complex trait and has many biological pathways related to muscle and fat. There is a need to identify functional modules or genes related to marbling traits and investigate their relationships through a weighted gene co-expression network analysis based on the system level. Therefore, we investigated the co-expression relationships of genes related to the ‘marbling score’ trait and systemically analyzed the network topology in Hanwoo (Korean cattle. As a result, we determined 3 modules (gene groups that showed statistically significant results for marbling score. In particular, one module (denoted as red has a statistically significant result for marbling score (p = 0.008 and intramuscular fat (p = 0.02 and water capacity (p = 0.006. From functional enrichment and relationship analysis of the red module, the pathway hub genes (IL6, CHRNE, RB1, INHBA and NPPA have a direct interaction relationship and share the biological functions related to fat or muscle, such as adipogenesis or muscle growth. This is the first gene network study with m.logissimus in Hanwoo to observe co-expression patterns in divergent marbling phenotypes. It may provide insights into the functional mechanisms of the marbling trait.

  13. Extracting microRNA-gene relations from biomedical literature using distant supervision.

    Directory of Open Access Journals (Sweden)

    Andre Lamurias

    Full Text Available Many biomedical relation extraction approaches are based on supervised machine learning, requiring an annotated corpus. Distant supervision aims at training a classifier by combining a knowledge base with a corpus, reducing the amount of manual effort necessary. This is particularly useful for biomedicine because many databases and ontologies have been made available for many biological processes, while the availability of annotated corpora is still limited. We studied the extraction of microRNA-gene relations from text. MicroRNA regulation is an important biological process due to its close association with human diseases. The proposed method, IBRel, is based on distantly supervised multi-instance learning. We evaluated IBRel on three datasets, and the results were compared with a co-occurrence approach as well as a supervised machine learning algorithm. While supervised learning outperformed on two of those datasets, IBRel obtained an F-score 28.3 percentage points higher on the dataset for which there was no training set developed specifically. To demonstrate the applicability of IBRel, we used it to extract 27 miRNA-gene relations from recently published papers about cystic fibrosis. Our results demonstrate that our method can be successfully used to extract relations from literature about a biological process without an annotated corpus. The source code and data used in this study are available at https://github.com/AndreLamurias/IBRel.

  14. Effects of parathyroid hormone and calcitonin on alkaline phosphatase activity and matrix calcification in rabbit growth-plate chondrocyte cultures

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Y.; Shimazu, A.; Nakashima, K.; Suzuki, F.; Jikko, A.; Iwamoto, M. (Osaka Univ. (Japan))

    1990-07-01

    The effects of PTH and calcitonin (CT) on the expression of mineralization-related phenotypes by chondrocytes were examined. In cultures of pelleted growth-plate chondrocytes. PTH caused 60-90% decreases in alkaline phosphatase activity, the incorporation of {sup 45}Ca into insoluble material, and the calcium content during the post-mitotic stage. These effects of PTH were dose-dependent and reversible. In contrast, CT increased alkaline phosphatase activity, {sup 45}Ca incorporation into insoluble material, and the calcium content by 1.4- to 1.8-fold. These observations suggest that PTH directly inhibits the expression of the mineralization-related phenotypes by growth-plate chondrocytes, and that CT has the opposite effects.

  15. 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

    -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...... antiobesity and antidiabetic efficacy by dual modulation of insulin sensitivity and directly decelerating stress on the pancreatic α- and β-cells. These results could provide the basis for oral KBP-042 as a novel therapeutic agent in type 2 diabetes....

  16. Mild to moderate increase of serum calcitonin levels only in presence of large medullary thyroid cancer deposits.

    Science.gov (United States)

    Pelizzo, M R; Torresan, F; Da Roit, A; Merante Boschin, I; Chondrogiannis, S; Rampin, L; Colletti, P M; Vinjamury, S; Perkins, A J; Rubello, D

    2015-01-01

    Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  17. Overview of vascular disease

    International Nuclear Information System (INIS)

    Bisset, G.S. III

    1998-01-01

    Vascular disease in the pediatric population is a poorly understood process which is often underestimated in its incidence. The common beginnings of such ubiquitous diseases as atherosclerosis manifest themselves at a cellular level shortly after birth. Other common systemic disorders, including congestive heart failure and sepsis, are also intricately associated with dysfunctional vasculature. Progress in the understanding of normal and pathophysiologic processes within the vascular system begins with the 'control center' - the endothelial cell. The purpose of this review is to consolidate a body of knowledge on the processes that occur at the cellular level within the blood vessel wall, and to simplify the understanding of how imbalances in these physiologic parameters result in vascular disease. (orig.)

  18. Diversification of Root Hair Development Genes in Vascular Plants.

    Science.gov (United States)

    Huang, Ling; Shi, Xinhui; Wang, Wenjia; Ryu, Kook Hui; Schiefelbein, John

    2017-07-01

    The molecular genetic program for root hair development has been studied intensively in Arabidopsis ( Arabidopsis thaliana ). To understand the extent to which this program might operate in other plants, we conducted a large-scale comparative analysis of root hair development genes from diverse vascular plants, including eudicots, monocots, and a lycophyte. Combining phylogenetics and transcriptomics, we discovered conservation of a core set of root hair genes across all vascular plants, which may derive from an ancient program for unidirectional cell growth coopted for root hair development during vascular plant evolution. Interestingly, we also discovered preferential diversification in the structure and expression of root hair development genes, relative to other root hair- and root-expressed genes, among these species. These differences enabled the definition of sets of genes and gene functions that were acquired or lost in specific lineages during vascular plant evolution. In particular, we found substantial divergence in the structure and expression of genes used for root hair patterning, suggesting that the Arabidopsis transcriptional regulatory mechanism is not shared by other species. To our knowledge, this study provides the first comprehensive view of gene expression in a single plant cell type across multiple species. © 2017 American Society of Plant Biologists. All Rights Reserved.

  19. Identification of a direct interaction between residue 19 in the helical portion of calcitonin and the amino-terminal domain of the calcitonin receptor from photoaffinity cross-linking and mutational studies

    International Nuclear Information System (INIS)

    Pham, V.; Wade, J.; McDowall, S.G.; Quiza, M.; Sexton, P.M.

    2001-01-01

    Full text: Calcitonins (CTs) are 32 amino acid hormones with both peripheral and central actions mediated via specific cell surface receptors, which belong to the superfamily of class II G-protein coupled receptors. Chimeric receptor and mutational data suggested that the helical portion (residues 8-22) of salmon CT (sCT) is important for high affinity binding to the amino-terminal extracellular domain of the human CT receptor (hCTR). In this study, we have developed photoactive sCT analogues [Arg 11, 18 , Bpa 19 ]sCT and [Arg 11 , 18 , Bpa 19 ]sCT(8-32) that incorporate a photolabile Bpa (p-benzoyl-L-phenylalanine) into position 19 of the helical domain of the ligand and used this to determine a specific receptor fragment proximate to it. These analogues saturably bound to the CTR with high affinity (IC 50 = 3 nM) which was similar to that of the natural sCT and its antagonist (IC 50 = 2 nM and 20 nM, respectively). Upon photolysis, radioiodinated 125 I-[Arg 11, 18 , Bpa 19 ]sCT and 125 I-[Arg 11,18 , Bpa 19 ]sCT(8-32) efficiently and specifically cross-linked to hCTR stably expressed in baby hamster kidney cells (Hollexl cells, ∼ 800,000 receptors per cell), generating a single radiolabeled band of ∼ 72-kDa on SDS/PAGE autoradiography. To identify the 'contact domain' within CTR involved in binding of 125 I-[Arg1 1 , 18 , Bpa 19 ]sCT and 125 I-[Arg 11, 18 , Bpa 19 ]sCT(8-32), the radiolabeled band containing the ligand-receptor conjugate was subjected to chemical and enzymatic cleavage. Cyanogen bromide cleavage of the native receptor yielded a radiolabeled fragment of apparent Mr ∼ 31-kDa that shifted to Mr ∼ 14 kDa after deglycosylation. This receptor domain corresponded to amino acids 59-134 of the hCTR, located at the amino-terminal extracellular region of the receptor. These results provide the first direct demonstration of a contact domain between calcitonin and its receptor, and will contribute towards the modelling of CT-CTR interface. Copyright

  20. Renal posttransplant's vascular complications

    Directory of Open Access Journals (Sweden)

    Bašić Dragoslav

    2003-01-01

    Full Text Available INTRODUCTION Despite high graft and recipient survival figures worldwide today, a variety of technical complications can threaten the transplant in the postoperative period. Vascular complications are commonly related to technical problems in establishing vascular continuity or to damage that occurs during donor nephrectomy or preservation [13]. AIM The aim of the presenting study is to evaluate counts and rates of vascular complications after renal transplantation and to compare the outcome by donor type. MATERIAL AND METHODS A total of 463 kidneys (319 from living related donor LD and 144 from cadaveric donor - CD were transplanted during the period between June 1975 and December 1998 at the Urology & Nephrology Institute of Clinical Centre of Serbia in Belgrade. Average recipients' age was 33.7 years (15-54 in LD group and 39.8 (19-62 in CD group. Retrospectively, we analyzed medical records of all recipients. Statistical analysis is estimated using Hi-squared test and Fischer's test of exact probability. RESULTS Major vascular complications including vascular anastomosis thrombosis, internal iliac artery stenosis, internal iliac artery rupture obliterant vasculitis and external iliac vein rupture were analyzed. In 25 recipients (5.4% some of major vascular complications were detected. Among these cases, 22 of them were from CD group vs. three from LD group. Relative rate of these complications was higher in CD group vs. LD group (p<0.0001. Among these complications dominant one was vascular anastomosis thrombosis which occurred in 18 recipients (17 from CD vs. one from LD. Of these recipients 16 from CD lost the graft, while the rest of two (one from each group had lethal outcome. DISCUSSION Thrombosis of renal allograft vascular anastomosis site is the most severe complication following renal transplantation. In the literature, renal allograft thrombosis is reported with different incidence rates, from 0.5-4% [14, 15, 16]. Data from the

  1. Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes.

    Science.gov (United States)

    Gooi, J H; Pompolo, S; Karsdal, M A; Kulkarni, N H; Kalajzic, I; McAhren, S H M; Han, B; Onyia, J E; Ho, P W M; Gillespie, M T; Walsh, N C; Chia, L Y; Quinn, J M W; Martin, T J; Sims, N A

    2010-06-01

    The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administration, we administered a low dose of the transient osteoclast inhibitor salmon calcitonin (sCT) to young rats receiving an anabolic PTH regimen. Co-administration of sCT significantly blunted the anabolic effect of PTH as measured by peripheral quantitative computer tomography (pQCT) and histomorphometry in the femur and tibia, respectively. To determine gene targets of sCT, we carried out quantitative real time PCR and microarray analysis of metaphyseal samples 1.5, 4 and 6.5h after administration of a single injection of PTH, sCT or PTH+sCT. Known targets of PTH action, IL-6, ephrinB2 and RANKL, were not modified by co-administration with sCT. Surprisingly, at all time points, we noted a significant upregulation of sclerostin mRNA by sCT treatment, as well as down-regulation of two other osteocyte gene products, MEPE and DMP1. Immunohistochemistry confirmed that sCT administration increased the percentage of osteocytes expressing sclerostin, suggesting a mechanism by which sCT reduced the anabolic effect of PTH. Neither mRNA for CT receptor (Calcr) nor labeled CT binding could be detected in sclerostin-enriched cells differentiated from primary calvarial osteoblasts. In contrast, osteocytes freshly isolated from calvariae expressed a high level of Calcr mRNA. Furthermore immunohistochemistry revealed co-localization of CT receptor (CTR) and sclerostin in some osteocytes in calvarial sections. Taken together these data indicate that co-treatment with sCT can blunt the anabolic effect of PTH and this may involve direct stimulation of sclerostin production by osteocytes. These data directly implicate calcitonin as a negative regulator of bone formation through a previously

  2. Identification of genes related to Paulownia witches' broom by AFLP and MSAP.

    Science.gov (United States)

    Cao, Xibing; Fan, Guoqiang; Deng, Minjie; Zhao, Zhenli; Dong, Yanpeng

    2014-08-21

    DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches' broom (PaWB) infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS) using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L(-1) MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR) showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB.

  3. Identification of Genes Related to Paulownia Witches’ Broom by AFLP and MSAP

    Science.gov (United States)

    Cao, Xibing; Fan, Guoqiang; Deng, Minjie; Zhao, Zhenli; Dong, Yanpeng

    2014-01-01

    DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches’ broom (PaWB) infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS) using amplified fragment length polymorphism (AFLP) and methylation-sensitive amplification polymorphism (MSAP) techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L−1 MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR) showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB. PMID:25196603

  4. Identification of Genes Related to Paulownia Witches’ Broom by AFLP and MSAP

    Directory of Open Access Journals (Sweden)

    Xibing Cao

    2014-08-01

    Full Text Available DNA methylation is believed to play important roles in regulating gene expression in plant growth and development. Paulownia witches’ broom (PaWB infection has been reported to be related to gene expression changes in paulownia plantlets. To determine whether DNA methylation is associated with gene expression changes in response to phytoplasma, we investigated variations in genomic DNA sequence and methylation in PaWB plantlets treated with methyl methane sulfonate (MMS using amplified fragment length polymorphism (AFLP and methylation-sensitive amplification polymorphism (MSAP techniques, respectively. The results indicated that PaWB seedings recovered a normal morphology after treatment with more than 15 mg·L−1 MMS. PaWB infection did not cause changes of the paulownia DNA sequence at the AFLP level; However, DNA methylation levels and patterns were altered. Quantitative real-time PCR (qRT-PCR showed that three of the methylated genes were up-regulated and three were down-regulated in the MMS-treated PaWB plantlets that had regained healthy morphology. These six genes might be involved in transcriptional regulation, plant defense, signal transduction and energy. The possible roles of these genes in PaWB are discussed. The results showed that changes of DNA methylation altered gene expression levels, and that MSAP might help identify genes related to PaWB.

  5. Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.

    Science.gov (United States)

    Guerrini, Renzo; Parrini, Elena

    2012-12-01

    Rett syndrome is an X-linked neurodevelopmental disorder that manifests in early childhood with developmental stagnation, and loss of spoken language and hand use, with the development of distinctive hand stereotypies, severe cognitive impairment, and autistic features. About 60% of patients have epilepsy. Seizure onset before the age of 3 years is unlikely, and onset after age 20 is rare. Diagnosis of Rett syndrome is based on key clinical elements that identify "typical" Rett syndrome but also "variant" or "atypical" forms. Diagnostic criteria have been modified only slightly over time, even after discovering that MECP2 gene alterations are present in >90% of patients with typical Rett syndrome but only in 50-70% of atypical cases. Over the last several years, intragenic or genomic alterations of the CDKL5 and FOXG1 genes have been associated with severe cognitive impairment, early onset epilepsy and, often, dyskinetic movement disorders, which have variably been defined as Rett variants. It is now clearly emerging that epilepsy has distinctive characteristics in typical Rett syndrome and in the different syndromes caused by CDKL5 and FOXG1 gene alterations. The progressive parting of CDKL5- and FOXG1-gene-related encephalopathies from the core Rett syndrome is reflected by the effort to produce clearer diagnostic criteria for typical and atypical Rett syndrome. Efforts to characterize the molecular pathology underlying these developmental encephalopathies are pointing to abnormalities of telencephalic development, neuronal morphogenesis, maturation and maintenance, and dendritic arborization. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

  6. Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin Color Differentiation in Red Tilapia.

    Science.gov (United States)

    Zhu, Wenbin; Wang, Lanmei; Dong, Zaijie; Chen, Xingting; Song, Feibiao; Liu, Nian; Yang, Hui; Fu, Jianjun

    2016-08-11

    Red tilapia is becoming more popular for aquaculture production in China in recent years. However, the pigmentation differentiation in genetic breeding is the main problem limiting its development of commercial red tilapia culture and the genetic basis of skin color variation is still unknown. In this study, we conducted Illumina sequencing of transcriptome on three color variety red tilapia. A total of 224,895,758 reads were generated, resulting in 160,762 assembled contigs that were used as reference contigs. The contigs of red tilapia transcriptome had hits in the range of 53.4% to 86.7% of the unique proteins of zebrafish, fugu, medaka, three-spined stickleback and tilapia. And 44,723 contigs containing 77,423 simple sequence repeats (SSRs) were identified, with 16,646 contigs containing more than one SSR. Three skin transcriptomes were compared pairwise and the results revealed that there were 148 common significantly differentially expressed unigenes and several key genes related to pigment synthesis, i.e. tyr, tyrp1, silv, sox10, slc24a5, cbs and slc7a11, were included. The results will facilitate understanding the molecular mechanisms of skin pigmentation differentiation in red tilapia and accelerate the molecular selection of the specific strain with consistent skin colors.

  7. Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Diaz-Villasenor, Andrea; Burns, Anna L.; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2007-01-01

    Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the impairment of the expression of genes related to type 2 diabetes by arsenic as one of the possible mechanisms by which it leads to the disease. Many factors are involved in the manner in which arsenic contributes to the occurrence of diabetes. The reviewed studies suggest that arsenic might increase the risk for type 2 diabetes via multiple mechanisms, affecting a cluster of regulated events, which in conjunction trigger the disease. Arsenic affects insulin sensitivity in peripheral tissue by modifying the expression of genes involved in insulin resistance and shifting away cells from differentiation to the proliferation pathway. In the liver arsenic disturbs glucose production, whereas in pancreatic beta-cells arsenic decreases insulin synthesis and secretion and reduces the expression of antioxidant enzymes. The consequences of these changes in gene expression include the reduction of insulin secretion, induction of oxidative stress in the pancreas, alteration of gluconeogenesis, abnormal proliferation and differentiation pattern of muscle and adipocytes as well as peripheral insulin resistance

  8. Major Vascular Neurocognitive Disorder: A Reappraisal to Vascular Dementia

    Directory of Open Access Journals (Sweden)

    Emre Kumral

    2017-03-01

    Full Text Available Major vascular neurocognitive disorder (NCD is the second leading form of dementia after Alzheimer’s disease, accounting for 17-20% of all dementias. Vascular NCD is a progressive disease caused by reduced cerebral blood flow related to multiple large volume or lacunar infarcts that induce a sudden onset and stepwise decline in cognitive abilities. Despite its prevalence and clinical importance, there is still controversy in the terminology of vascular NCD. Only after the release of Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5 (2013 did the American Psychiatric Association define vascular dementia as “major vascular NCD”. This review includes an overview of risk factors, pathophysiology, types, diagnostic and clinical features of major vascular NCD, and current treatment options of vascular NCD regarding to DSM-5 criteria

  9. Plant Vascular Biology 2010

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Biao

    2014-11-17

    This grant supported the Second International Conference on Plant Vascular Biology (PVB 2010) held July 24-28, 2010 on the campus of Ohio State University, Columbus, Ohio. Biao Ding (Ohio State University; OSU) and David Hannapel (Iowa State University; ISU) served as co-chairs of this conference. Biao Ding served as the local organizer. PVB is defined broadly here to include studies on the biogenesis, structure and function of transport systems in plants, under conditions of normal plant growth and development as well as of plant interactions with pathogens. The transport systems cover broadly the xylem, phloem, plasmodesmata and vascular cell membranes. The PVB concept has emerged in recent years to emphasize the integrative nature of the transport systems and approaches to investigate them.

  10. Vascular cognitive impairment

    Directory of Open Access Journals (Sweden)

    N.V. Vakhnina

    2014-01-01

    Full Text Available Vascular pathology of the brain is the second most common cause of cognitive impairment after Alzheimer's disease. The article describes the modern concepts of etiology, pathogenetic mechanisms, clinical features and approaches to diagnosis and therapy of vascular cognitive impairment (VCI. Cerebrovascular accident, chronic cerebral circulatory insufficiency and their combination, sometimes in combination with a concomitant neurodegenerative process, are shown to be the major types of brain lesions leading to VCI. The clinical presentation of VCI is characterized by the neuropsychological status dominated by impairment of the executive frontal functions (planning, control, attention in combination with focal neurological symptoms. The diagnosis is based on comparing of the revealed neuropsychological and neurological features with neuroimaging data. Neurometabolic, acetylcholinergic, glutamatergic, and other vasoactive drugs and non-pharmacological methods are widely used to treat VCI. 

  11. Vascular Surgery and Robotics

    Directory of Open Access Journals (Sweden)

    Indrani Sen

    2016-01-01

    Full Text Available The application of robotics to Vascular surgery has not progressed as rapidly as of endovascular technology, but this is changing with the amalgamation of these two fields. The advent of Endovascular robotics is an exciting field which overcomes many of the limitations of endovascular therapy like vessel tortuosity and operator fatigue. This has much clinical appeal for the surgeon and hold significant promise of better patient outcomes. As with most newer technological advances, it is still limited by cost and availability. However, this field has seen some rapid progress in the last decade with the technology moving into the clinical realm. This review details the development of robotics, applications, outcomes, advantages, disadvantages and current advances focussing on Vascular and Endovascular robotics

  12. Vascular lesions following radiation

    International Nuclear Information System (INIS)

    Fajardo, L.F.; Berthrong, M.

    1988-01-01

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury

  13. Vascular lumen formation.

    Science.gov (United States)

    Lammert, Eckhard; Axnick, Jennifer

    2012-04-01

    The vascular system developed early in evolution. It is required in large multicellular organisms for the transport of nutrients, oxygen, and waste products to and from tissues. The vascular system is composed of hollow tubes, which have a high level of complexity in vertebrates. Vasculogenesis describes the de novo formation of blood vessels, e.g., aorta formation in vertebrate embryogenesis. In contrast, angiogenesis is the formation of blood vessels from preexisting ones, e.g., sprouting of intersomitic blood vessels from the aorta. Importantly, the lumen of all blood vessels in vertebrates is lined and formed by endothelial cells. In both vasculogenesis and angiogenesis, lumen formation takes place in a cord of endothelial cells. It involves a complex molecular mechanism composed of endothelial cell repulsion at the cell-cell contacts within the endothelial cell cords, junctional rearrangement, and endothelial cell shape change. As the vascular system also participates in the course of many diseases, such as cancer, stroke, and myocardial infarction, it is important to understand and make use of the molecular mechanisms of blood vessel formation to better understand and manipulate the pathomechanisms involved.

  14. Pulmonary vascular imaging

    International Nuclear Information System (INIS)

    Fedullo, P.F.; Shure, D.

    1987-01-01

    A wide range of pulmonary vascular imaging techniques are available for the diagnostic evaluation of patients with suspected pulmonary vascular disease. The characteristics of any ideal technique would include high sensitivity and specificity, safety, simplicity, and sequential applicability. To date, no single technique meets these ideal characteristics. Conventional pulmonary angiography remains the gold standard for the diagnosis of acute thromboembolic disease despite the introduction of newer techniques such as digital subtraction angiography and magnetic resonance imaging. Improved noninvasive lower extremity venous testing methods, particularly impedance plethysmography, and ventilation-perfusion scanning can play significant roles in the noninvasive diagnosis of acute pulmonary emboli when properly applied. Ventilation-perfusion scanning may also be useful as a screening test to differentiate possible primary pulmonary hypertension from chronic thromboembolic pulmonary hypertension. And, finally, angioscopy may be a useful adjunctive technique to detect chronic thromboembolic disease and determine operability. Optimal clinical decision-making, however, will continue to require the proper interpretation of adjunctive information obtained from the less-invasive techniques, applied with an understanding of the natural history of the various forms of pulmonary vascular disease and with a knowledge of the capabilities and shortcomings of the individual techniques

  15. Characteristics of multi-organ lymphangiectasia resulting from temporal deletion of calcitonin receptor-like receptor in adult mice.

    Directory of Open Access Journals (Sweden)

    Samantha L Hoopes

    Full Text Available Adrenomedullin (AM and its receptor complexes, calcitonin receptor-like receptor (Calcrl and receptor activity modifying protein 2/3, are highly expressed in lymphatic endothelial cells and are required for embryonic lymphatic development. To determine the role of Calcrl in adulthood, we used an inducible Cre-loxP system to temporally and ubiquitously delete Calcrl in adult mice. Following tamoxifen injection, Calcrl(fl/fl/CAGGCre-ER™ mice rapidly developed corneal edema and inflammation that was preceded by and persistently associated with dilated corneoscleral lymphatics. Lacteals and submucosal lymphatic capillaries of the intestine were also dilated, while mesenteric collecting lymphatics failed to properly transport chyle after an acute Western Diet, culminating in chronic failure of Calcrl(fl/fl/CAGGCre-ER™ mice to gain weight. Dermal lymphatic capillaries were also dilated and chronic edema challenge confirmed significant and prolonged dermal lymphatic insufficiency. In vivo and in vitro imaging of lymphatics with either genetic or pharmacologic inhibition of AM signaling revealed markedly disorganized lymphatic junctional proteins ZO-1 and VE-cadherin. The maintenance of AM signaling during adulthood is required for preserving normal lymphatic permeability and function. Collectively, these studies reveal a spectrum of lymphatic defects in adult Calcrl(fl/fl/CAGGCre-ER™ mice that closely recapitulate the clinical symptoms of patients with corneal, intestinal and peripheral lymphangiectasia.

  16. Characteristics of multi-organ lymphangiectasia resulting from temporal deletion of calcitonin receptor-like receptor in adult mice.

    Science.gov (United States)

    Hoopes, Samantha L; Willcockson, Helen H; Caron, Kathleen M

    2012-01-01

    Adrenomedullin (AM) and its receptor complexes, calcitonin receptor-like receptor (Calcrl) and receptor activity modifying protein 2/3, are highly expressed in lymphatic endothelial cells and are required for embryonic lymphatic development. To determine the role of Calcrl in adulthood, we used an inducible Cre-loxP system to temporally and ubiquitously delete Calcrl in adult mice. Following tamoxifen injection, Calcrl(fl/fl)/CAGGCre-ER™ mice rapidly developed corneal edema and inflammation that was preceded by and persistently associated with dilated corneoscleral lymphatics. Lacteals and submucosal lymphatic capillaries of the intestine were also dilated, while mesenteric collecting lymphatics failed to properly transport chyle after an acute Western Diet, culminating in chronic failure of Calcrl(fl/fl)/CAGGCre-ER™ mice to gain weight. Dermal lymphatic capillaries were also dilated and chronic edema challenge confirmed significant and prolonged dermal lymphatic insufficiency. In vivo and in vitro imaging of lymphatics with either genetic or pharmacologic inhibition of AM signaling revealed markedly disorganized lymphatic junctional proteins ZO-1 and VE-cadherin. The maintenance of AM signaling during adulthood is required for preserving normal lymphatic permeability and function. Collectively, these studies reveal a spectrum of lymphatic defects in adult Calcrl(fl/fl)/CAGGCre-ER™ mice that closely recapitulate the clinical symptoms of patients with corneal, intestinal and peripheral lymphangiectasia.

  17. Radioimmunoassay of human calcitonin in serum and tissue from healthy individuals and patients with medullary carcinoma of the thyroid gland

    International Nuclear Information System (INIS)

    Gautvik, K.M.; Normann, T.; Teig, V.; Wille, S.Oe.; Brennhovd, I.O.; Christensen, I.

    1976-01-01

    A specific radioimmunological method for measurement of immunoreactive calcitonin (iCT) in human serum and tissue is described. Of healthy individuals of both sexes, 85 % had measurable iCT in serum (mean, 0.23 ng/ml). Of 29 patients who had received treatment for medullary carcinoma of the thyroid gland (MCT), 19 had increased serum iCT (0-60 ng/ml to205 ng/ml). Elevated serum iCT was also found preoperatively in 2 MCT patients. Eleven of the patients with abnormal elevations of serum iCT were alive 4 to 13 years after the operation. Concentration of iCT in extracts from MCT varied from 0.5 to 540 ng/ml wet weight. The diagnostic value of this method and its importance for pre- and post-operative evaluation of these patients are improved by the use of selective venous catheterization in basal state and during stimulation of CT secretion. (Auth.)

  18. Calcitonin protects chondrocytes from lipopolysaccharide-induced apoptosis and inflammatory response through MAPK/Wnt/NF-κB pathways.

    Science.gov (United States)

    Zhang, Lai-Bo; Man, Zhen-Tao; Li, Wei; Zhang, Wei; Wang, Xian-Quan; Sun, Shui

    2017-07-01

    Calcitonin (CT) is an anti-absorbent, which has long been used for treatment of osteoporosis. However, little information is available about the effects of CT on osteoarthritis (OA). This study was mainly aimed to explore the effects of CT on the treatment of OA, as well as the underlying mechanisms. Chondrocytes were isolated from immature mice and then were incubated with lipopolysaccharide (LPS), CT, small interfering (si) RNA against bone morphogenetic protein (BMP)-2, and/or the inhibitors of MAPK/Wnt/NF-κB pathway. Thereafter, cell viability, apoptosis, nitric oxide (NO) and inflammatory factors productions, and expression levels of cartilage synthesis protein key factors, cartilage-derived morphogenetic protein (CDMP) 1, SRY (sex-determining region Y)-box 9 protein (SOX9), and MAPK/Wnt/NF-κB pathways key factors were determined. CT significantly reversed LPS-induced cell viability decrease, apoptosis increase, the inflammatory factors and NO secretion, the abnormally expression of cartilage synthesis proteins and the activation of MAPK/Wnt/NF-κB pathways (Ppathways statistically further increased the levels of CDMP1 and SOX9 (Ppathways, and could partially abolish CT-modulated the expression changes in CDMP1 and SOX9, and MAPK/Wnt/NF-κB pathways key factors (Ppathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Essential Role for Hypothalamic Calcitonin Receptor‒Expressing Neurons in the Control of Food Intake by Leptin.

    Science.gov (United States)

    Pan, Warren; Adams, Jessica M; Allison, Margaret B; Patterson, Christa; Flak, Jonathan N; Jones, Justin; Strohbehn, Garth; Trevaskis, James; Rhodes, Christopher J; Olson, David P; Myers, Martin G

    2018-04-01

    The adipocyte-derived hormone leptin acts via its receptor (LepRb) on central nervous system neurons to communicate the repletion of long-term energy stores, to decrease food intake, and to promote energy expenditure. We generated mice that express Cre recombinase from the calcitonin receptor (Calcr) locus (Calcrcre mice) to study Calcr-expressing LepRb (LepRbCalcr) neurons, which reside predominantly in the arcuate nucleus (ARC). Calcrcre-mediated ablation of LepRb in LepRbCalcrknockout (KO) mice caused hyperphagic obesity. Because LepRb-mediated transcriptional control plays a crucial role in leptin action, we used translating ribosome affinity purification followed by RNA sequencing to define the transcriptome of hypothalamic Calcr neurons, along with its alteration in LepRbCalcrKO mice. We found that ARC LepRbCalcr cells include neuropeptide Y (NPY)/agouti-related peptide (AgRP)/γ-aminobutyric acid (GABA) ("NAG") cells as well as non-NAG cells that are distinct from pro-opiomelanocortin cells. Furthermore, although LepRbCalcrKO mice exhibited dysregulated expression of several genes involved in energy balance, neither the expression of Agrp and Npy nor the activity of NAG cells was altered in vivo. Thus, although direct leptin action via LepRbCalcr cells plays an important role in leptin action, our data also suggest that leptin indirectly, as well as directly, regulates these cells.

  20. Evaluation of salmon calcitonin (sCT) enteric-coated capsule for enhanced absorption and GI tolerability in rats.

    Science.gov (United States)

    Wu, Lei; Zhang, Ge; Lu, Qin; Sun, Qian; Wang, Mulan; Li, Na; Gao, Zidong; Sun, Ya; Li, Tingting; Han, Deen; Yu, Xue; Wang, Lei; Sun, Wei; Zhao, Di; Wu, Yaning; Lu, Yang; Chen, Xijing

    2010-03-01

    Considering the chronic and repeated nature of salmon calcitonin (sCT) therapy, the oral route is a preferred route of administration. But, the oral bioavailability of sCT is very low due to enzymatic degradation and poor permeation across intestinal epithelial cells. It was the aim of this study to investigate the pharmacodynamic (PD), pharmacokinetic (PK), and mucosal injury characteristic of sCT oral delivery system. In this study, PD experiments were performed to find a suitable releasing region of sCT, an effect absorption enhancer, and an optimal mass ratio of sCT/enhancer. In addition, the PK experiments were designed to validate the absorption enhancement of this oral delivery system. Histopathological evaluations on the intestinal mucosa were carried out to assess any potential toxicity of the absorption enhancer. Through the PD research, we determined that oral sCT enteric-coated capsules containing sCT and citric acid (CA) with a ratio of 1:20 may be an adaptable delivery. PK study further proved that the oral absorption of sCT was enhanced from this delivery system. Finally, no damage on intestinal mucosa was observed when rats received the delivery system containing CA for up to 7 days. These results suggested that enteric-coated capsules with a certain amount of CA might give enhanced oral delivery of peptide drugs like sCT.

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

    Science.gov (United States)

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

    2011-05-01

    During all stages of protein drug development, aggregation is one of the most often encountered problems. Covalent conjugation of poly(ethylene glycol) (PEG), also called PEGylation, to proteins has been shown to reduce aggregation of proteins. In this paper, new excipients based on PEG are presented that are able to reduce aggregation of salmon calcitonin (sCT). Several PEG polymers consisting of a hydrophobic dansyl-headgroup attached to PEGs of different molecular weights have been synthesized and characterized physicochemically. After addition of dansyl-methoxypoly(ethylene glycol) (mPEG) 2 kDa to a 40 times molar excess of sCT resulted in an increase in dansyl-fluorescence and a decrease in 90° light scatter suggesting possible interactions. The aggregation of sCT in different buffer systems in presence or absence of the different dansyl-PEGs was measured by changes in Nile red fluorescence and turbidity. Dansyl-mPEG 2 kDa in a 1:1 molar ratio to sCT strongly reduced aggregation. Reduction of sCT aggregation was also measured for the bivalent dansyl-PEG 3 kDa in a 1:1 molar ratio. Dansyl-mPEG 5 kDa deteriorated sCT aggregation. Potential cytotoxicity and hemolysis were investigated. This paper shows that dansyl-PEGs are efficacious in reducing aggregation of sCT. Copyright © 2010 Wiley-Liss, Inc.

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

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2014-01-01

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

  3. Vascular remodeling and mineralocorticoids.

    Science.gov (United States)

    Weber, K T; Sun, Y; Campbell, S E; Slight, S H; Ganjam, V K

    1995-01-01

    Circulating mineralocorticoid hormones are so named because of their important homeostatic properties that regulate salt and water balance via their action on epithelial cells. A broader range of functions in nonclassic target cellular sites has been proposed for these steroids and includes their contribution to wound healing following injury. A chronic, inappropriate (relative to intravascular volume and dietary sodium intake) elevation of these circulating hormones evokes a wound healing response in the absence of tissue injury--a wound healing response gone awry. The adverse remodeling of vascularized tissues seen in association with chronic mineralocorticoid excess is the focus of this review.

  4. Natural Selection on Genes Related to Cardiovascular Health in High-Altitude Adapted Andeans.

    Science.gov (United States)

    Crawford, Jacob E; Amaru, Ricardo; Song, Jihyun; Julian, Colleen G; Racimo, Fernando; Cheng, Jade Yu; Guo, Xiuqing; Yao, Jie; Ambale-Venkatesh, Bharath; Lima, João A; Rotter, Jerome I; Stehlik, Josef; Moore, Lorna G; Prchal, Josef T; Nielsen, Rasmus

    2017-11-02

    The increase in red blood cell mass (polycythemia) due to the reduced oxygen availability (hypoxia) of residence at high altitude or other conditions is generally thought to be beneficial in terms of increasing tissue oxygen supply. However, the extreme polycythemia and accompanying increased mortality due to heart failure in chronic mountain sickness most likely reduces fitness. Tibetan highlanders have adapted to high altitude, possibly in part via the selection of genetic variants associated with reduced polycythemic response to hypoxia. In contrast, high-altitude-adapted Quechua- and Aymara-speaking inhabitants of the Andean Altiplano are not protected from high-altitude polycythemia in the same way, yet they exhibit other adaptive features for which the genetic underpinnings remain obscure. Here, we used whole-genome sequencing to scan high-altitude Andeans for signals of selection. The genes showing the strongest evidence of selection-including BRINP3, NOS2, and TBX5-are associated with cardiovascular development and function but are not in the response-to-hypoxia pathway. Using association mapping, we demonstrated that the haplotypes under selection are associated with phenotypic variations related to cardiovascular health. We hypothesize that selection in response to hypoxia in Andeans could have vascular effects and could serve to mitigate the deleterious effects of polycythemia rather than reduce polycythemia itself. Copyright © 2017. Published by Elsevier Inc.

  5. Expression Analysis of Genes Related to Rice Resistance Against Brown Planthopper, Nilaparvata lugens

    Directory of Open Access Journals (Sweden)

    Panatda Jannoey

    2017-05-01

    Full Text Available Brown planthopper (BPH is an insect species that feeds on the vascular system of rice plants. To examine the defence mechanism of rice plants against BPH, the pathogenesis-related genes (PR1a, PR2, PR3, PR4, PR6, PR9, PR10a, PR13, PR15 and PRpha, signaling molecule synthesis genes (AOS, AXR, ACO and LOX, antioxidant-related genes (CAT, TRX, GST and SOD and lignin biosynthesis-related genes (CHS, CHI and C4H were investigated in a resistant rice variety. AOS, PR6, PR9 and PR15 genes showed significantly increased relative expression levels at 24.38-, 19.17-, 14.71-, and 12.74-fold compared to the control. Moderate increased relative expression levels of lignin biosynthesis-related gene (C4H, pathogenesis-related genes (PR4, PR10a and PRpha, and antioxidant-related gene (GST were found, while CHI, LOX, SOD, TRX1 and AXR showed decreased relative expression levels. It was thus clearly shown that wound-induced response genes were activated in rice plants after BPH attacks through AOS activation. Jasmonic acid signaling molecule may activate PR6, PR15, GST and CAT subsequently increasing their expression for H2O2 detoxification. PR6 were expressed at the highest relative level among the PR genes. These genes therefore have also a considerable synergistic role with the other genes against BPH by interfered their digestion tract system.

  6. Interventional vascular radiology

    International Nuclear Information System (INIS)

    Yune, H.Y.

    1984-01-01

    The papers published during this past year in the area of interventional vascular radiology presented some useful modifications and further experiences both in the area of thromboembolic therapy and in dilation and thrombolysis, but no new techniques. As an introductory subject, an excellent monograph reviewing the current spectrum of pharmacoangiography was presented in Radiographics. Although the presented material is primarily in diagnostic application of various pharmacologic agents used today to facilitate demonstration of certain diagnostic criteria of various disease processes, both vasodilatory and vasoconstrictive reaction to these agents are widely used in various therapeutic vascular procedures. This monograph should be reviewed by every angiographer whether or not he or she performs interventional procedures, and it would be very convenient to have this table available in the angiography suite. In a related subject, Bookstein and co-workers have written an excellent review concerning pharmacologic manipulations of various blood coagulative parameters during angiography. Understanding the proper method of manipulation of the bloodclotting factors during angiography, and especially during interventional angiography, is extremely important. Particularly, the method of manipulating the coagulation with the use of heparin and protamine and modification of the platelet activity by using aspirin and dipyridamole are succinctly reviewed. The systemic and selective thrombolytic activities of streptokianse are also discussed

  7. Vascular dysfunction in preeclampsia.

    Science.gov (United States)

    Brennan, Lesley J; Morton, Jude S; Davidge, Sandra T

    2014-01-01

    Preeclampsia is a complex disorder which affects an estimated 5% of all pregnancies worldwide. It is diagnosed by hypertension in the presence of proteinuria after the 20th week of pregnancy and is a prominent cause of maternal morbidity and mortality. As delivery is currently the only known treatment, preeclampsia is also a leading cause of preterm delivery. Preeclampsia is associated with maternal vascular dysfunction, leading to serious cardiovascular risk both during and following pregnancy. Endothelial dysfunction, resulting in increased peripheral resistance, is an integral part of the maternal syndrome. While the cause of preeclampsia remains unknown, placental ischemia resulting from aberrant placentation is a fundamental characteristic of the disorder. Poor placentation is believed to stimulate the release of a number of factors including pro- and antiangiogenic factors and inflammatory activators into the maternal systemic circulation. These factors are critical mediators of vascular function and impact the endothelium in distinctive ways, including enhanced endothelial oxidative stress. The mechanisms of action and the consequences on the maternal vasculature will be discussed in this review. © 2013 John Wiley & Sons Ltd.

  8. Vascular Remodeling in Experimental Hypertension

    Directory of Open Access Journals (Sweden)

    Norma R. Risler

    2005-01-01

    Full Text Available The basic hemodynamic abnormality in hypertension is an increased peripheral resistance that is due mainly to a decreased vascular lumen derived from structural changes in the small arteries wall, named (as a whole vascular remodeling. The vascular wall is an active, flexible, and integrated organ made up of cellular (endothelial cells, smooth muscle cells, adventitia cells, and fibroblasts and noncellular (extracellular matrix components, which in a dynamic way change shape or number, or reorganize in response to physiological and pathological stimuli, maintaining the integrity of the vessel wall in physiological conditions or participating in the vascular changes in cardiovascular diseases such as hypertension. Research focused on new signaling pathways and molecules that can participate in the mechanisms of vascular remodeling has provided evidence showing that vascular structure is not only affected by blood pressure, but also by mechanisms that are independent of the increased pressure. This review will provide an overview of the evidence, explaining some of the pathophysiologic mechanisms participating in the development of the vascular remodeling, in experimental models of hypertension, with special reference to the findings in spontaneously hypertensive rats as a model of essential hypertension, and in fructose-fed rats as a model of secondary hypertension, in the context of the metabolic syndrome. The understanding of the mechanisms producing the vascular alterations will allow the development of novel pharmacological tools for vascular protection in hypertensive disease.

  9. Vascular pattern formation in plants.

    Science.gov (United States)

    Scarpella, Enrico; Helariutta, Ykä

    2010-01-01

    Reticulate tissue systems exist in most multicellular organisms, and the principles underlying the formation of cellular networks have fascinated philosophers, mathematicians, and biologists for centuries. In particular, the beautiful and varied arrangements of vascular tissues in plants have intrigued mankind since antiquity, yet the organizing signals have remained elusive. Plant vascular tissues form systems of interconnected cell files throughout the plant body. Vascular cells are aligned with one another along continuous lines, and vascular tissues differentiate at reproducible positions within organ environments. However, neither the precise path of vascular differentiation nor the exact geometry of vascular networks is fixed or immutable. Several recent advances converge to reconcile the seemingly conflicting predictability and plasticity of vascular tissue patterns. A control mechanism in which an apical-basal flow of signal establishes a basic coordinate system for body axis formation and vascular strand differentiation, and in which a superimposed level of radial organizing cues elaborates cell patterns, would generate a reproducible tissue configuration in the context of an underlying robust, self-organizing structure, and account for the simultaneous regularity and flexibility of vascular tissue patterns. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Association of calcitonin receptor gene (CALCR) polymorphism with kidney stone disease in the population of West Bengal, India.

    Science.gov (United States)

    Mitra, Pubali; Guha, Manalee; Ghosh, Sudakshina; Mukherjee, Sourav; Bankura, Biswabandhu; Pal, Dilip Kumar; Maity, Biswanath; Das, Madhusudan

    2017-07-30

    Kidney Stone Disease (KSD) is a complex urologic disorder with strong genetic constituent. Earlier association studies have indicated that the genetic polymorphisms are the potential cause of stone materialization; however unfortunately, the actual genetic signature is still unknown. Therefore, present study was aimed to investigate the potential contribution of two important polymorphisms of calcitonin receptor gene (CALCR): (i) rs1801197 (Leu447Pro) and (ii) rs1042138 (3'UTR+18C>T) in renal stone formation. Accordingly, we enrolled 152 patients registered with calcium-rich stone in kidney (case) and 144 corresponding age, sex and ethnicity matched healthy individuals (controls). Epidemiological and clinical data were recorded as well as peripheral blood sample was collected from each individual. Serum creatinine and urinary calcium level was found high in patients, compared to controls. Out of two studied polymorphisms, we have not found any significant association against the rs1042138 with KSD, nonetheless, significant high frequency (p=0.001; Odds ratio=1.81; 95% CI: 1.28-2.55) of risk allele T against the rs1801197 (T>C) in patient was noted. Moreover, significant association with KSD was noted by genotypic analysis of rs1801197 (Leu447Pro) in our population. Interestingly, male patients carrying TT genotype was found to be at high risk of stone formation, while no such association was observed in female patients. Altogether, present study indicated that the rs1042138 might not be used as a useful marker for susceptibility of kidney stone formation, whereas, the rs1801197 could definitely be considered as one of the risk factors for KSD in Indian population at least in West Bengal in particular. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis.

    Science.gov (United States)

    Bagger, Yu Z; Tankó, László B; Alexandersen, Peter; Karsdal, Morten A; Olson, Melvin; Mindeholm, Linda; Azria, Moïse; Christiansen, Claus

    2005-09-01

    To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the baseline level of cartilage turnover. This was a randomized, double blind, placebo-controlled clinical setting including 152 Danish postmenopausal women aged 55-85. The subjects received treatment with the different doses of sCT (0.15, 0.4, 1.0, or 2.5 mg) combined with Eligen technology-based carrier molecule (200 mg), or placebo for 3 months. The efficacy parameter was the changes in the 24-h excretion of urinary CTX-I/II corrected for creatinine excretion at month 3. sCT induced a significant dose-dependent decrease in 24-h urinary CTX-II excretion. Similar dose-dependent responses were found in 24-h urinary CTX-I. When stratifying the study population into tertiles of baseline urinary CTX-II, the present osteoarthritic symptoms and definite cases of osteoarthritis (OA) were significantly more frequent in women in the highest tertile of CTX-II (mean 391 +/- 18 ng/mmol). Women who received 1.0 mg of sCT and had the highest cartilage turnover presented the greatest decrease in urinary CTX-II after 3 months of treatment. In addition to its pronounced effect on bone resorption, this novel oral sCT formulation may also reduce cartilage degradation and thereby provide therapeutic benefit in terms of chondroprotection. Women with high cartilage turnover are more likely to benefit from oral sCT treatment.

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

    Directory of Open Access Journals (Sweden)

    Hyeogsun Kwon

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

  13. Additive Manufacturing of Vascular Grafts and Vascularized Tissue Constructs.

    Science.gov (United States)

    Elomaa, Laura; Yang, Yunzhi Peter

    2017-10-01

    There is a great need for engineered vascular grafts among patients with cardiovascular diseases who are in need of bypass therapy and lack autologous healthy blood vessels. In addition, because of the severe worldwide shortage of organ donors, there is an increasing need for engineered vascularized tissue constructs as an alternative to organ transplants. Additive manufacturing (AM) offers great advantages and flexibility of fabrication of cell-laden, multimaterial, and anatomically shaped vascular grafts and vascularized tissue constructs. Various inkjet-, extrusion-, and photocrosslinking-based AM techniques have been applied to the fabrication of both self-standing vascular grafts and porous, vascularized tissue constructs. This review discusses the state-of-the-art research on the use of AM for vascular applications and the key criteria for biomaterials in the AM of both acellular and cellular constructs. We envision that new smart printing materials that can adapt to their environment and encourage rapid endothelialization and remodeling will be the key factor in the future for the successful AM of personalized and dynamic vascular tissue applications.

  14. Cardiac and vascular malformations

    International Nuclear Information System (INIS)

    Ley, S.; Ley-Zaporozhan, J.

    2015-01-01

    Malformations of the heart and great vessels show a high degree of variation. There are numerous variants and defects with only few clinical manifestations and are only detected by chance, such as a persistent left superior vena cava or a partial anomalous pulmonary venous connection. Other cardiovascular malformations are manifested directly after birth and need prompt mostly surgical interventions. At this point in time echocardiography is the diagnostic modality of choice for morphological and functional characterization of malformations. Additional imaging using computed tomography (CT) or magnetic resonance imaging (MRI) is only required in a minority of cases. If so, the small anatomical structures, the physiological tachycardia and tachypnea are a challenge for imaging modalities and strategies. This review article presents the most frequent vascular, cardiac and complex cardiovascular malformations independent of the first line diagnostic imaging modality. (orig.) [de

  15. CIRSE Vascular Closure Device Registry

    NARCIS (Netherlands)

    Reekers, Jim A.; Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2011-01-01

    Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. The CIRSE registry of closure devices

  16. Dynamic adaption of vascular morphology

    DEFF Research Database (Denmark)

    Okkels, Fridolin; Jacobsen, Jens Christian Brings

    2012-01-01

    The structure of vascular networks adapts continuously to meet changes in demand of the surrounding tissue. Most of the known vascular adaptation mechanisms are based on local reactions to local stimuli such as pressure and flow, which in turn reflects influence from the surrounding tissue. Here ...

  17. Diagnostic criteria for vascular dementia

    NARCIS (Netherlands)

    Scheltens, P.; Hijdra, A. H.

    1998-01-01

    The term vascular dementia implies the presence of a clinical syndrome (dementia) caused by, or at least assumed to be caused by, a specific disorder (cerebrovascular disease). In this review, the various sets of criteria used to define vascular dementia are outlined. The various sets of criteria

  18. The vascular secret of Klotho

    DEFF Research Database (Denmark)

    Lewin, Ewa; Olgaard, Klaus

    2015-01-01

    Klotho is an evolutionarily highly conserved protein related to longevity. Increasing evidence of a vascular protecting effect of the Klotho protein has emerged and might be important for future treatments of uremic vascular calcification. It is still disputed whether Klotho is locally expressed ...

  19. Social media in vascular surgery.

    Science.gov (United States)

    Indes, Jeffrey E; Gates, Lindsay; Mitchell, Erica L; Muhs, Bart E

    2013-04-01

    There has been a tremendous growth in the use of social media to expand the visibility of various specialties in medicine. The purpose of this paper is to describe the latest updates on some current applications of social media in the practice of vascular surgery as well as existing limitations of use. This investigation demonstrates that the use of social networking sites appears to have a positive impact on vascular practice, as is evident through the incorporation of this technology at the Cleveland Clinic and by the Society for Vascular Surgery into their approach to patient care and physician communication. Overall, integration of social networking technology has current and future potential to be used to promote goals, patient awareness, recruitment for clinical trials, and professionalism within the specialty of vascular surgery. Copyright © 2013 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  20. Intestinal absorption of /sup 47/Ca in elderly patients with osteoporosis, Paget's disease, and osteomalacia. Effects of calcitonin, oestrogen, and vitamin D2

    Energy Technology Data Exchange (ETDEWEB)

    Lender, M.; Verner, E.; Stankiewicz, H.; Menczel, J.

    1977-01-01

    The intestinal absorption of /sup 47/Ca was studied in elderly patients. A standard dose of 10 ..mu..Ci of /sup 47/Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60--80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 ..mu..g once daily per os for 10 days proved to increase /sup 47/Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.

  1. Lipeo-sCT: a novel reversible lipidized salmon calcitonin derivative, its biophysical properties and hypocalcemic activity.

    Science.gov (United States)

    Cheng, Weiqiang; Lim, Lee-Yong

    2009-05-12

    We have previously described the design and synthesis of Mal-sCT and compared its biological activity with its reversible counterpart, REAL-sCT. Mal-sCT was salmon calcitonin (sCT) conjugated with two molecules of an epsilon-maleimido lysine derivative of palmitic acid via non-reversible thioether bonds at its cysteine residues while REAL-sCT was sCT conjugated with two molecules of a cysteine derivative of palmitic acid via reducible disulfide bonds at its cysteine residues. Neither compounds when dissolved in water could reproducibly improved the oral deliverability of sCT. The purpose of this study was to characterize and evaluate Lipeo-sCT, a novel sCT analog conjugated via reducible disulfide bonds with two amphiphilic groups consisting of a hydrophobic hexadecyl moiety attached via an ether bond to a hydrophilic triethylene glycol moiety. Lipeo-sCT was successfully synthesized by a 4-step reaction, purified and identified by ESI-MS. Analysis by dynamic light scattering (DLS) and transmission electron microscopy (TEM) suggested it had a propensity to form aggregates in water, although the aggregation behavior was controllable by modulating solvent polarity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicated a lack of cytotoxicity against the Caco-2 cells at up to 100 microM. Compared with sCT, Lipeo-sCT lowered plasma calcium to comparable levels when injected subcutaneously at 0.15 mg/kg into female Wistar rats, but the hypocalcemic activity of Lipeo-sCT was prolonged by at least 6 more hours. This was attributable to a continual regeneration of sCT from Lipeo-sCT. sCT was detectable in plasma 8h following subcutaneous injection of Lipeo-sCT (1.90 mg/kg), while Lipeo-sCT was not observed in plasma at all time points. By comparison, sCT was detectable in plasma for less than 2.5h following subcutaneous injection at an equivalent dose (1.50mg/kg). Data from this study complement those of previous studies, and add to the body of

  2. 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

  3. Vascular disease in cocaine addiction.

    Science.gov (United States)

    Bachi, Keren; Mani, Venkatesh; Jeyachandran, Devi; Fayad, Zahi A; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-07-01

    Cocaine, a powerful vasoconstrictor, induces immune responses including cytokine elevations. Chronic cocaine use is associated with functional brain impairments potentially mediated by vascular pathology. Although the Crack-Cocaine epidemic has declined, its vascular consequences are increasingly becoming evident among individuals with cocaine use disorder of that period, now aging. Paradoxically, during the period when prevention efforts could make a difference, this population receives psychosocial treatment at best. We review major postmortem and in vitro studies documenting cocaine-induced vascular toxicity. PubMed and Academic Search Complete were used with relevant terms. Findings consist of the major mechanisms of cocaine-induced vasoconstriction, endothelial dysfunction, and accelerated atherosclerosis, emphasizing acute, chronic, and secondary effects of cocaine. The etiology underlying cocaine's acute and chronic vascular effects is multifactorial, spanning hypertension, impaired homeostasis and platelet function, thrombosis, thromboembolism, and alterations in blood flow. Early detection of vascular disease in cocaine addiction by multimodality imaging is discussed. Treatment may be similar to indications in patients with traditional risk-factors, with few exceptions such as enhanced supportive care and use of benzodiazepines and phentolamine for sedation, and avoiding β-blockers. Given the vascular toxicity cocaine induces, further compounded by smoking and alcohol comorbidity, and interacting with aging of the crack generation, there is a public health imperative to identify pre-symptomatic markers of vascular impairments in cocaine addiction and employ preventive treatment to reduce silent disease progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. [The future of vascular medicine].

    Science.gov (United States)

    Kroeger, K; Luther, B

    2014-10-01

    In the future vascular medicine will still have a great impact on health of people. It should be noted that the aging of the population does not lead to a dramatic increase in patient numbers, but will be associated with a changing spectrum of co-morbidities. In addition, vascular medical research has to include the intensive care special features of vascular patients, the involvement of vascular medicine in a holistic concept of fast-track surgery, a geriatric-oriented intensive monitoring and early geriatric rehabilitation. For the future acceptance of vascular medicine as a separate subject area under delimitation of cardiology and radiology is important. On the other hand, the subject is so complex and will become more complex in future specialisations that mixing of surgery and angiology is desirable, with the aim to preserve the vascular surgical knowledge and skills on par with the medical and interventional measures and further develop them. Only large, interdisciplinary guided vascular centres will be able to provide timely diagnosis and therapy, to deal with the growing multi-morbidity of the patient, to perform complex therapies even in an acute emergency and due to sufficient number of cases to present with well-trained and experienced teams. These requirements are mandatory to decrease patients' mortality step by step. Georg Thieme Verlag KG Stuttgart · New York.

  5. Contemporary vascular smartphone medical applications.

    Science.gov (United States)

    Carter, Thomas; O'Neill, Stephen; Johns, Neil; Brady, Richard R W

    2013-08-01

    Use of smartphones and medical mHealth applications (apps) within the clinical environment provides a potential means for delivering elements of vascular care. This article reviews the contemporary availability of apps specifically themed to major vascular diseases and the opportunities and concerns regarding their integration into practice. Smartphone apps relating to major vascular diseases were identified from the app stores for the 6 most popular smartphone platforms, including iPhone, Android, Blackberry, Nokia, Windows, and Samsung. Search terms included peripheral artery (arterial) disease, varicose veins, aortic aneurysm, carotid artery disease, amputation, ulcers, hyperhydrosis, thoracic outlet syndrome, vascular malformation, and lymphatic disorders. Forty-nine vascular-themed apps were identified. Sixteen (33%) were free of charge. Fifteen apps (31%) had customer satisfaction ratings, but only 3 (6%) had greater than 100. Only 13 apps (27%) had documented medical professional involvement in their design or content. The integration of apps into the delivery of care has the potential to benefit vascular health care workers and patients. However, high-quality apps designed by clinicians with vascular expertise are currently lacking and represent an area of concern in the mHealth market. Improvement in the quality and reliability of these apps will require the development of robust regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Constructal vascularized structures

    Science.gov (United States)

    Cetkin, Erdal

    2015-06-01

    Smart features such as self-healing and selfcooling require bathing the entire volume with a coolant or/and healing agent. Bathing the entire volume is an example of point to area (or volume) flows. Point to area flows cover all the distributing and collecting kinds of flows, i.e. inhaling and exhaling, mining, river deltas, energy distribution, distribution of products on the landscape and so on. The flow resistances of a point to area flow can be decreased by changing the design with the guidance of the constructal law, which is the law of the design evolution in time. In this paper, how the flow resistances (heat, fluid and stress) can be decreased by using the constructal law is shown with examples. First, the validity of two assumptions is surveyed: using temperature independent Hess-Murray rule and using constant diameter ducts where the duct discharges fluid along its edge. Then, point to area types of flows are explained by illustrating the results of two examples: fluid networks and heating an area. Last, how the structures should be vascularized for cooling and mechanical strength is documented. This paper shows that flow resistances can be decreased by morphing the shape freely without any restrictions or generic algorithms.

  7. Diabetes and Retinal Vascular Dysfunction

    Directory of Open Access Journals (Sweden)

    Eui Seok Shin

    2014-01-01

    Full Text Available Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR. We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR.

  8. Vascular graft infections with Mycoplasma

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Skov Jensen, J; Prag, J

    1995-01-01

    laboratory techniques, the percentage of culture-negative yet grossly infected vascular grafts seems to be increasing and is not adequately explained by the prior use of antibiotics. We have recently reported the first case of aortic graft infection with Mycoplasma. We therefore suggest the hypothesis...... that the large number of culture-negative yet grossly infected vascular grafts may be due to Mycoplasma infection not detected with conventional laboratory technique....

  9. Limb vascular function in women

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Gliemann, Lasse

    2018-01-01

    Throughout life, women are subjected to both acute fluctuations in sex hormones, associated with the menstrual cycle, and chronic changes following the onset of menopause. Female sex hormones, and in particular estrogen, strongly influence cardiovascular function such as the regulation of vascular...... studies. Physical activity should be recommended for women of all ages, but the most essential timing for maintenance of vascular health may be from menopause and onwards....

  10. Facial vascular malformations in children

    International Nuclear Information System (INIS)

    Brunelle, F.O.; Lallemand, D.; Chaumont, P.; Teillac, D.; Manach, Y.

    1988-01-01

    The authors present their experience with conventional and digital angiography of vascular malformations of the head and neck in children. 22 hemangioendotheliomas, 8 venous angiomas, and 3 arteriovenous fistula were studied. 22 patients were embolised. DSA offers many advantages during the diagnostic as well as during the therapeutic phase of angiography. Embolization appears to have a major role in treatment of such vascular malformations. (orig.)

  11. Angiogenesis, Cancer, and Vascular Aging

    Directory of Open Access Journals (Sweden)

    Junji Moriya

    2017-10-01

    Full Text Available Several lines of evidence have revealed that the angiogenic response to ischemic injury declines with age, which might account for the increased morbidity and mortality of cardiovascular disease (CVD among the elderly. While impairment of angiogenesis with aging leads to delayed wound healing or exacerbation of atherosclerotic ischemic diseases, it also inhibits the progression of cancer. Age-related changes of angiogenesis have been considered to at least partly result from vascular aging or endothelial cell senescence. There is considerable evidence supporting the hypothesis that vascular cell senescence contributes to the pathogenesis of age-related CVD, suggesting that vascular aging could be an important therapeutic target. Since therapeutic angiogenesis is now regarded as a promising concept for patients with ischemic CVD, it has become even more important to understand the detailed molecular mechanisms underlying impairment of angiogenesis in older patients. To improve the usefulness of therapeutic angiogenesis, approaches are needed that can compensate for impaired angiogenic capacity in the elderly while not promoting the development or progression of malignancy. In this review, we briefly outline the mechanisms of angiogenesis and vascular aging, followed by a description of how vascular aging leads to impairment of angiogenesis. We also examine potential therapeutic approaches that could enhance angiogenesis and/or vascular function in the elderly, as well as discussing the possibility of anti-senescence therapy or reversal of endothelial cell senescence.

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

    Science.gov (United States)

    Rawat, Atul; Kumar, Dinesh

    2013-01-01

    Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(α) chemical shifts and three bond H(N) -H(α) coupling constants indicated that most of the residues of the peptide are populating the α-helical region of the Ramachandran (ϕ, ψ) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (10(2) -10(3)  s(-1) ), inferred by the multiple chemical shift assignments in the region Leu4-Leu12 and around Pro23 (for residues Gln20-Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self-association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The (15) N NMR-relaxation data revealed (i) the presence of slow (microsecond-to-millisecond) timescale dynamics in the N-terminal region (Cys1-Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond-to-picosecond) motions in the C-terminal arm. Put together, the various results suggested that (i) the flexible C-terminal of sCT (from Thr25-Thr31) is involved in identification of specific target receptors, (ii) whereas the N-terminal of sCT (from Cys1-Gln20) in solution - exhibiting significant amount of conformational plasticity and strong bias towards biologically active α-helical structure - facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs. Copyright © 2012 European Peptide

  13. Calcium dynamics in vascular smooth muscle

    OpenAIRE

    Amberg, Gregory C.; Navedo, Manuel F.

    2013-01-01

    Smooth muscle cells are ultimately responsible for determining vascular luminal diameter and blood flow. Dynamic changes in intracellular calcium are a critical mechanism regulating vascular smooth muscle contractility. Processes influencing intracellular calcium are therefore important regulators of vascular function with physiological and pathophysiological consequences. In this review we discuss the major dynamic calcium signals identified and characterized in vascular smooth muscle cells....

  14. Injuries to the vascular endothelium: vascular wall and endothelial dysfunction.

    Science.gov (United States)

    Fisher, Mark

    2008-01-01

    Vascular endothelial injury has multiple elements, and this article focuses on ischemia-related processes that have particular relevance to ischemic stroke. Distinctions between necrotic and apoptotic cell death provide a basic science context in which to better understand the significance of classical core and penumbra concepts of acute stroke, with apoptotic processes particularly prominent in the penumbra. The mitochondria are understood to serve as a reservoir of proteins that mediate apoptosis. Oxidative stress pathways generating reactive oxygen species (ROS) are prominent in endothelial injury, both ischemic and nonischemic, with prominent roles of enzyme- and nonenzymemediated pathways; mitochondria once again have a critical role, particularly in the nonenzymatic pathways generating ROS. Inflammation also contributes to vascular endothelial injury, and endothelial cells have the capacity to rapidly increase expression of inflammatory mediators following ischemic challenge; this leads to enhanced leukocyte-endothelial interactions mediated by selectins and adhesion molecules. Preconditioning consists of a minor version of an injurious event, which in turn may protect vascular endothelium from injury following a more substantial event. Presence of the blood-brain barrier creates unique responses to endothelial injury, with permeability changes due to impairment of endothelial-matrix interactions compounding altered vasomotor tone and tissue perfusion mediated by nitric oxide. Pharmacological protection against vascular endothelial injury can be provided by several of the phosphodiesterases (cilostazol and dipyridamole), along with statins. Optimal clinical responses for protection of brain vascular endothelium may use preconditioning as a model, and will likely require combined protection against apoptosis, ROS, and inflammation.

  15. Non-invasive vascular imaging: assessing tumour vascularity

    International Nuclear Information System (INIS)

    Delorme, S.; Knopp, M.V.

    1998-01-01

    Non-invasive assessment of vascularity is a new diagnostic approach to characterise tumours. Vascular assessment is based on the pathophysiology of tumour angiogenesis and its diagnostic implications for tumour biology, prognosis and therapy response. Two current techniques investigating vascular features in addition to morphology are Doppler ultrasonography and contrast-enhanced MRI. Diagnostic differentiation has been shown to be possible with Doppler, and a high degree of observed vascularity could be linked to an aggressive course of the disease. Dynamic MRI using gadolinium chelates is already used clinically to detect and differentiate tumours. The histological correlation shows that capillary permeability is increased in malignant tumours and is the best criterion for differentiation from benign processes. Permeability and perfusion factors seem to be more diagnostic than overall vessel density. New clinical applications are currently being established for therapy monitoring. Further instrumental developments will bring harmonic imaging in Doppler, and faster imaging techniques, higher spatial resolution and novel pharmacokinetic concepts in MRI. Upcoming contrast agents for both Doppler and MRI will further improve estimation of intratumoural blood volume and vascular permeability. (orig.)

  16. Watery diarrhea syndrome in an adult with ganglioneuroma-pheochromocytoma: identification of vasoactive intestinal peptide, calcitonin, and catecholamines and assessment of their biologic activity.

    Science.gov (United States)

    Trump, D L; Livingston, J N; Baylin, S B

    1977-10-01

    A case of adult ganglioneuroma-pheochromocytoma with an associated watery diarrhea syndrome is reported. High levels of vasoactive intestinal peptide (VIP) were found in preoperative serum and in tumor tissue. The serum VIP levels fell to normal, and the watery diarrhae syndrome completely ceased following removal of the tumor. In addition to containing VIP, the tumor was rich in catecholamines, and calcitonin. Peptide hormone-containing extracts and catecholamine extracts from the tumor both activated the adenyl cyclase system and increased lipolytic activity in a preparation of isolated rat fat cells. The findings in this patient further link VIP with neural crest tissues, and suggest the importance of determining catecholamine levels in patients with the watery diarrhea syndrome.

  17. 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...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...... determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy....

  18. 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)

    Gimbo, E.K.

    1989-01-01

    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 125 I-hCT free of high molecular weight contaminats. A repurification on polyacrylamide gel electrophoresis provided 125 I-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 (GP 2 -IPEN) could be used in such a dilution (1:4000) to provide highly sensitive curves (minimal detectable concentration [pt

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    Background and Purpose Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges – hence, development of weight loss therapies with the ability to reduce the co-morbidities is key. Experimental Approach The effect of the dual...... amylin and calcitonin receptor agonist (DACRA), KBP-089, on bodyweight, glucose homeostasis, and fatty acid accumulation in liver and muscle tissue, food preference was investigated. Further, we elucidate weight-independent effects of KBP-089 using a weight-matched group. Key Results High fat diet fed...... improved glucose homeostasis through improved insulin action. To obtain a weight-matched group, significantly less food was offered (9% less than in the KBP-089 group). Weight-matching led to improved glucose homeostasis through lowered plasma insulin; however, these were inferior to the effect of KBP-089...

  20. 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.

  1. Pediatric interventional radiology: vascular interventions

    International Nuclear Information System (INIS)

    Kandasamy, Devasenathipathy; Gamanagatti, Shivanand; Gupta, Arun Kumar

    2016-01-01

    Pediatric interventional radiology (PIR) comprises a range of minimally invasive diagnostic and therapeutic procedures that are performed using image guidance. PIR has emerged as an essential adjunct to various surgical and medical conditions. Over the years, technology has undergone dramatic and continuous evolution, making this speciality grow. In this review, the authors will discuss various vascular interventional procedures undertaken in pediatric patients. It is challenging for the interventional radiologist to accomplish a successful interventional procedure. There are many vascular interventional radiology procedures which are being performed and have changed the way the diseases are managed. Some of the procedures are life saving and have become the treatment of choice in those patients. The future is indeed bright for the practice and practitioners of pediatric vascular and non-vascular interventions. As more and more of the procedures that are currently being performed in adults get gradually adapted for use in the pediatric population, it may be possible to perform safe and successful interventions in many of the pediatric vascular lesions that are otherwise being referred for surgery. (author)

  2. Fetal origin of vascular aging

    Directory of Open Access Journals (Sweden)

    Shailesh Pitale

    2011-01-01

    Full Text Available Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke. It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD. These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ′Barker′s Hypothesis′. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

  3. Imaging after vascular gene therapy

    International Nuclear Information System (INIS)

    Manninen, Hannu I.; Yang, Xiaoming

    2005-01-01

    Targets for cardiovascular gene therapy currently include limiting restenosis after balloon angioplasty and stent placement, inhibiting vein bypass graft intimal hyperplasia/stenosis, therapeutic angiogenesis for cardiac and lower-limb ischemia, and prevention of thrombus formation. While catheter angiography is still standard method to follow-up vascular gene transfer, other modern imaging techniques, especially intravascular ultrasound (IVUS), magnetic resonance (MR), and positron emission tomography (PET) imaging provide complementary information about the therapeutic effect of vascular gene transfer in humans. Although molecular imaging of therapeutic gene expression in the vasculatures is still in its technical development phase, it has already offered basic medical science an extremely useful in vivo evaluation tool for non- or minimally invasive imaging of vascular gene therapy

  4. Association of variants in genes related to the immune response and obesity with BPH in CLUE II.

    Science.gov (United States)

    Lopez, D S; Peskoe, S B; Tsilidis, K K; Hoffman-Bolton, J; Helzlsouer, K J; Isaacs, W B; Smith, M W; Platz, E A

    2014-12-01

    Chronic inflammation and obesity may contribute to the genesis or progression of BPH and BPH-associated lower urinary tract symptoms (LUTS). The influence of variants in genes related to these states on BPH has not been studied extensively. Thus, we evaluated the association of 17 single-nucleotide polymorphisms (SNPs) in immune response genes (IL1B, IL6, IL8, IL10, TNF, CRP, TLR4 and RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG and TCF7L2), with BPH. BPH cases (N = 568) and age-frequency matched controls (N=568) were selected from among adult male CLUE II cohort participants who responded in 2000 to a mailed questionnaire. BPH was defined as BPH surgery, use of BPH medications or symptomatic BPH (American Urological Association Symptom Index Score ⩾ 15). Controls were men who had not had BPH surgery, did not use BPH medications and whose symptom score was ⩽ 7. Age-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. None of the candidate SNPs was statistically significantly associated with BPH. However, we could not rule out possible weak associations for CRP rs1205 (1082C>T), ADIPOQ rs1501299 (276C>A), PPARG rs1801282 (-49C>G) and TCF7L2 rs7903146 (47833T>C). After summing risk alleles, men with ⩾ 4 had an increased BPH risk compared with those with ⩽ 1 (OR, 1.78; 95% CI, 1.10-2.89; P(trend) = 0.006). SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH.

  5. Vascular Gene Expression: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Angélica Concepción eMartínez-Navarro

    2013-07-01

    Full Text Available The phloem is the conduit through which photoassimilates are distributed from autotrophic to heterotrophic tissues and is involved in the distribution of signaling molecules that coordinate plant growth and responses to the environment. Phloem function depends on the coordinate expression of a large array of genes. We have previously identified conserved motifs in upstream regions of the Arabidopsis genes, encoding the homologs of pumpkin phloem sap mRNAs, displaying expression in vascular tissues. This tissue-specific expression in Arabidopsis is predicted by the overrepresentation of GA/CT-rich motifs in gene promoters. In this work we have searched for common motifs in upstream regions of the homologous genes from plants considered to possess a primitive vascular tissue (a lycophyte, as well as from others that lack a true vascular tissue (a bryophyte, and finally from chlorophytes. Both lycophyte and bryophyte display motifs similar to those found in Arabidopsis with a significantly low E-value, while the chlorophytes showed either a different conserved motif or no conserved motif at all. These results suggest that these same genes are expressed coordinately in non- vascular plants; this coordinate expression may have been one of the prerequisites for the development of conducting tissues in plants. We have also analyzed the phylogeny of conserved proteins that may be involved in phloem function and development. The presence of CmPP16, APL, FT and YDA in chlorophytes suggests the recruitment of ancient regulatory networks for the development of the vascular tissue during evolution while OPS is a novel protein specific to vascular plants.

  6. [Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

    Science.gov (United States)

    Kurabayashi, Masahiko

    2015-05-01

    Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

  7. Vascular malforma- tions part 1 — normal and abnormal vascular ...

    African Journals Online (AJOL)

    Enrique

    to form the primitive vascular plexus. Angiogenesis is the formation of new vessels by sprouting or splitting of ... The differentiation of primitive vessels into arteries, veins or capillaries is determined by flow patterns .... identify, but it is probable that as time progresses further specific genetic defects related to the development ...

  8. Genetic Regulation of Vascular Development: Building the Zebrafish Vascular Tree

    NARCIS (Netherlands)

    R.L.J.M. Herpers (Robert)

    2010-01-01

    textabstractThe extensive networks of blood and lymphatic vessels within the vertebrate body are essential for the transport and delivery of fluids, gases, macromolecules and cells, and play important roles in facilitating immune responses. The development of the vascular tree requires a highly

  9. [Vascular access guidelines for hemodialysis].

    Science.gov (United States)

    Rodríguez Hernández, J A; González Parra, E; Julián Gutiérrez, J M; Segarra Medrano, A; Almirante, B; Martínez, M T; Arrieta, J; Fernández Rivera, C; Galera, A; Gallego Beuter, J; Górriz, J L; Herrero, J A; López Menchero, R; Ochando, A; Pérez Bañasco, V; Polo, J R; Pueyo, J; Ruiz, Camps I; Segura Iglesias, R

    2005-01-01

    Quality of vascular access (VA) has a remarkable influence in hemodialysis patients outcomes. Dysfunction of VA represents a capital cause of morbi-mortality of these patients as well an increase in economical. Spanish Society of Neprhology, aware of the problem, has decided to carry out a revision of the issue with the aim of providing help in comprehensión and treatment related with VA problems, and achieving an homogenization of practices in three mayor aspects: to increase arteriovenous fistula utilization as first vascular access, to increment vascular access monitoring practice and rationalise central catheters use. We present a consensus document elaborated by a multidisciplinar group composed by nephrologists, vascular surgeons, interventional radiologysts, infectious diseases specialists and nephrological nurses. Along six chapters that cover patient education, creation of VA, care, monitoring, complications and central catheters, we present the state of the art and propose guidelines for the best practice, according different evidence based degrees, with the intention to provide help at the professionals in order to make aproppiate decissions. Several quality standars are also included.

  10. Image Quality in Vascular Radiology

    International Nuclear Information System (INIS)

    Vanhavere, F.; Struelens, L.

    2005-01-01

    In vascular radiology, the radiologists use the radiological image to diagnose or treat a specific vascular structure. From literature, we know that related doses are high and that large dose variability exists between different hospitals. The application of the optimization principle is therefore necessary and is obliged by the new legislation. So far, very little fieldwork has been performed and no practical instructions are available to do the necessary work. It's indisputable that obtaining quantitative data is of great interest for optimization purposes. In order to gain insight into these doses and the possible measures for dose reduction, we performed a comparative study in 7 hospitals. Patient doses will be measured and calculated for specific procedures in vascular radiology and evaluated against their most influencing parameters. In view of optimization purposes, a protocol for dose audit will be set-up. From the results and conclusions in this study, experimentally based guidelines will be proposed, in order to improve clinical practice in vascular radiology

  11. Vascular aspects of multiple sclerosis

    NARCIS (Netherlands)

    D'haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; De Keyser, Jacques

    Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial

  12. Subclinical hypothyroidism after vascular complicated pregnancy

    NARCIS (Netherlands)

    Zanden, M. van der; Hop-de Groot, R.J.; Sweep, F.C.; Ross, H.A.; Heijer, M. den; Spaanderman, M.E.A.

    2013-01-01

    OBJECTIVE: Women with a history of vascular complicated pregnancy are at risk for developing remote cardiovascular disease. It is associated with underlying cardiovascular risk factors both jeopardizing trophoblast and vascular function. Subclinical hypothyroidism may relate to both conditions.

  13. Pediatric central nervous system vascular malformations

    International Nuclear Information System (INIS)

    Burch, Ezra A.; Orbach, Darren B.

    2015-01-01

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  14. Pediatric central nervous system vascular malformations

    Energy Technology Data Exchange (ETDEWEB)

    Burch, Ezra A. [Brigham and Women' s Hospital, Department of Radiology, Boston, MA (United States); Orbach, Darren B. [Boston Children' s Hospital, Neurointerventional Radiology, Boston, MA (United States)

    2015-09-15

    Pediatric central nervous system (CNS) vascular anomalies include lesions found only in the pediatric population and also the full gamut of vascular lesions found in adults. Pediatric-specific lesions discussed here include infantile hemangioma, vein of Galen malformation and dural sinus malformation. Some CNS vascular lesions that occur in adults, such as arteriovenous malformation, have somewhat distinct manifestations in children, and those are also discussed. Additionally, children with CNS vascular malformations often have associated broader vascular conditions, e.g., PHACES (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, eye anomalies and sternal anomalies), hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation syndrome (related to the RASA1 mutation). The treatment of pediatric CNS vascular malformations has greatly benefited from advances in endovascular therapy, including technical advances in adult interventional neuroradiology. Dramatic advances in therapy are expected to stem from increased understanding of the genetics and vascular biology that underlie pediatric CNS vascular malformations. (orig.)

  15. ESRD QIP - Vascular Access - Payment Year 2018

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes facility details, performance rates, vascular access topic measure score, and the state and national average measure scores for the vascular...

  16. Vascular neurocognitive disorders and the vascular risk factors

    Directory of Open Access Journals (Sweden)

    Carmen V. Albu

    2018-04-01

    Full Text Available Dementias are clinical neurodegenerative diseases characterized by permanent and progressive transformation of cognitive functions such as memory, learning capacity, attention, thinking, language, passing judgments, calculation or orientation. Dementias represent a relatively frequent pathology, encountered at about 10% of the population of 65-year olds and 20% of the population of 80-year olds. This review presents the main etiological forms of dementia, which include Alzheimer form of dementia, vascular dementia, dementia associated with alpha-synucleionopathies, and mixed forms. Regarding vascular dementia, the risk factors are similar to those for an ischemic or hemorrhagic cerebrovascular accident: arterial hypertension, diabetes mellitus, dyslipidemia, smoking, obesity, age, alcohol consumption, cerebral atherosclerosis/ arteriosclerosis. Several studies show that efficient management of the vascular risk factors can prevent the expression and/ or progression of dementia. Thus, lifestyle changes such as stress reduction, regular physical exercise, decreasing dietary fat, multivitamin supplementation, adequate control of blood pressure and serum cholesterol, and social integration and mental stimulation in the elderly population are important factors in preventing or limiting the symptoms of dementia, a disease with significant individual, social, and economic implications.

  17. Genotypes analysis of ten genes related to eating quality of 22 Shanghai important rice varieties by molecular marker

    Directory of Open Access Journals (Sweden)

    XIE Mixue

    2013-08-01

    Full Text Available The improvement of rice eating quality is a very important direction of rice breeding.Clearing the different genotype of rice eating quality provides the basis for the parent selection on breeding good eating quality rice.Using molecular marker detection technology,genotypes of ten genes related to eating quality of 22 Shanghai important rice varieties,including conventional rice and hybrid parents were detected.The results showed that "Zixiangnuo 861" rice contained many poor genotypes which might affect rice eating quality.The genotypes of 3 male parents,"Xiangqin","R44" and "Fan14" for three kinds of hybrid rice,"Hannyouxiangqing","Qiuyoujinfeng" and "Huayou14",respectively,were not as good as their corresponding female parents,"HanfengA","JinfengA" and "Shen9A" and another conventional rice varieties.Wx polymorphism analysis showed that there were two glutinous rice,four soft rice japonica and 16 non-soft rice japonica."Baonong34","Jinfeng" and "Yinxiang18" had relatively better genotypes of the genes controlling eating quality among the 16 non-soft rice japonica.

  18. [Comparative analysis of three treatment regimens for treating gonarthritis with calcitonin, naproxen and flavonoids based on EULAR criteria and visual analogue scale (VAS)].

    Science.gov (United States)

    Badurski, J; Jeziernicka, E; Naruszewicz, K; Racewicz, A

    1995-11-01

    The newest laboratory and clinical elaborations have described a stimulatory effect of salmon calcitonin (sCT) on cultivated chondrocytes and cartilage explants in regard to their secretory function of glycosaminoglycans, collagen t. II and hyaluonic acid as well as have shown anticatabolic effect of sCT on numerous animal models of osteoarthropathy. Moreover, very few clinical indicated profitable effect of CT on degenerative joint diseases and on rheumatoid arthritis. The aim of the present study is to compare the curative effect of sCT (Miacalcic, Sandoz, nasal spray, 2 x 100 IU/day ) vs flavonoides (VR, Venoruton, Zyma, 2 x 0.6 + Vit. C. 0.2/day) with or without naproxen sodium (AP, Apranax, 2 x 0.550/day) in 30 patients suffering from gonarthritis, treated in 10 months in one of the three regimes: I--(n = 10, BMI-33.3, aged 59.5 y., Larsen gr. -2.5): 1st month-VR, 2 and 3-sCT, 4 and 5-VR, 6 and 7-AP, 8.9 and 10-VR; II--(n = 10, BMI-28.8, aged 56 y., Larsen gr. 2.95): 1st m.-VR, 2 and 3-Ap, 4 and 5-VR, 6 and 7-sCT, 9.9 and 10-VR; III--(n = 10, BMI-31.4, aged 58 y., Larsen gr.-2.8): 1st m.-VR, 2 and 3-sCT, 4 and 5-VR, 6 and 7-sCT, 8.9 and 10-VR. Clinical effects of treatment were evaluated by EULAR criteria, VAS, and the paracetamol consumption. The best results according to all three criteria of improvement have been observed in group III treated only with sCT and VR followed by group I in which sCT was given as the first active drug. This effect lasted until three months after the withdrawal of sCT and/or naproxen. This results supported our opinion on antiosteoarthritic ability of salmon calcitonin and marked curative effect of flavonoides in the treatment of osteoarthritis.

  19. Vascularized osseous graft for scaphoid

    International Nuclear Information System (INIS)

    Mendez Daza, Carlos Hernan; Mathoulin, Cristophe

    2004-01-01

    The most commonly used technique for treatment of pseudo-arthrosis of the scaphoid is osteo-synthesis with Kirschnet wires and cortical sponge grafts. Results reported by different teams using this procedure show no more than 90% osseous consolidation, especially in cases where vascularisation of the proximal fragment of the scaphoid is compromised. Here we present a series of ten cases of pseudo-arthrosis of the scaphoid, treated using a new surgical technique involving a vascularized osseous graft of the distal radius. Using this procedure we obtained 100% consolidation, with no complications either during the procedure or immediately post-operatively. Patients returned to work in week 15 on average. In 4 cases we observed discomfort in the area of the scar, which was successfully treated using local cortisone injection. The results obtained are very similar to those seen in the literature on the different techniques for vascularized osseous grafts for pseudo-arthrosis of the scaphoid

  20. [Menopause: Hypertension and vascular disease].

    Science.gov (United States)

    Zilberman, J M

    Hypertension is the main cardiovascular risk factor affecting 25% of women. Hormone changes and hypertension after menopause may lead to higher target organ damage and cardiovascular disease such as increased arterial stiffness, coronary diseases, chronic heart failure and stroke. The physiopathological mechanisms involved in the development of hypertension and cardiovascular diseases in menopausal women are controversial. There are pharmacokinetic and pharmacodynamic differences in both sexes, the women have more coughing when using the converting-enzyme inhibitors, more cramps when using thiazide diuretics and more oedema in the inferior limbs when using calcium antagonists. The aim of this review is to analyse possible physiopathological mechanisms involved in hypertension after menopause and to gain a better understanding of the biological effects mediated by vascular ageing in women when the level of oestrogen protective effect decreases over the vascular system. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Vascular diagnostics for Raynaud's phenomenon

    Directory of Open Access Journals (Sweden)

    Dinsdale G

    2014-10-01

    Full Text Available Graham Dinsdale, Ariane L Herrick Centre for Musculoskeletal Research, Institute of Inflammation and Repair, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK Abstract: Raynaud's phenomenon (RP is common, and in most patients is primary (idiopathic when due to reversible vasospasm and does not progress to irreversible tissue injury. However, in those patients for whom RP is secondary to an underlying disease (eg, systemic sclerosis or atherosclerosis, progression to digital ulceration or critical ischemia can occur. Therefore, the key question for the clinician is “Why does this patient have RP?” Vascular diagnostics play a key role in answering this. In this review, we firstly discuss the different vascular investigations relevant to clinical practice: nail fold capillaroscopy (including the different methodologies for examining the nail fold capillaries, and the role of capillaroscopy in helping to differentiate between primary and systemic sclerosis-related RP, thermography (available in specialist centers, and evaluation of large vessel disease (for example, due to atherosclerosis. We then discuss research tools, mainly laser Doppler methods, including laser Doppler imaging and laser speckle contrast imaging. These are commercially available as complete imaging systems and are (relatively easy to use. The main current goal in vascular imaging research is to validate these novel state-of-the-art techniques as outcome measures of digital vascular disease, and then apply them in early and later phase studies of new treatment approaches, thus facilitating drug development programs. Keywords: Raynaud's phenomenon, systemic sclerosis, nail fold capillaroscopy, thermography, laser Doppler, angiography

  2. Effects of maternal smoking on the placental expression of genes related to angiogenesis and apoptosis during the first trimester.

    Directory of Open Access Journals (Sweden)

    Akihiro Kawashima

    Full Text Available Maternal cigarette smoking is reportedly associated with miscarriage, fetal growth restriction and placental abruption, and is paradoxically associated with a decreased risk of developing preeclampsia. In the present study, we investigated the gene expression levels of villous tissues in early gestation. We compared the expression levels of the genes related to angiogenesis and apoptosis in the villous tissues obtained from smoking and non-smoking pregnant women.We collected villous tissue samples from 57 women requesting surgical termination due to non-medical reasons at 6-8 weeks of gestation. The maternal cigarette smoking status was evaluated by the level of serum cotinine and patients were divided into active smokers and non-smokers by the serum cotinine level. The placental levels of VEGFA, PGF, FLT1, HIF1A, TP53, BAX and BCL2 mRNA were quantified by real time PCR.The gene expression level of PGF and HIF1A in the active smoker group was significantly higher than that in the non-smoker group. We did not observe any significant differences in the VEGFA or FLT1 expression between the groups. In active smoker group, the gene expression levels of TP53 and BAX were significantly higher than those in the non-smoker group. The ratio of BAX/BCL2 mRNA in the active smoker group was significantly higher than that in the non-smoker group.Our findings revealed that smoking might affect the placenta during early pregnancy. Maternal cigarette smoking in early pregnancy may be associated with villus hypoxia, which may influence angiogenesis and apoptosis.

  3. Transcriptomic analysis of a tertiary relict plant, extreme xerophyte Reaumuria soongorica to identify genes related to drought adaptation.

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    Yong Shi

    Full Text Available BACKGROUND: Reaumuria soongorica is an extreme xerophyte shrub widely distributed in the desert regions including sand dune, Gobi and marginal loess of central Asia which plays a crucial role to sustain and restore fragile desert ecosystems. However, due to the lacking of the genomic sequences, studies on R. soongorica had mainly limited in physiological responses to drought stress. Here, a deep transcriptomic sequencing of R. soongorica will facilitate molecular functional studies and pave the path to understand drought adaptation for a desert plant. METHODOLOGY/PRINCIPAL FINDINGS: A total of 53,193,660 clean paired-end reads was generated from the Illumina HiSeq™ 2000 platform. By assembly with Trinity, we got 173,700 contigs and 77,647 unigenes with mean length of 677 bp and N50 of 1109 bp. Over 55% (43,054 unigenes were successfully annotated based on sequence similarity against public databases as well as Rfam and Pfam database. Local BLAST and Kyoto Encyclopedia of Genes and Genomes (KEGG maps were used to further exhausting seek for candidate genes related to drought adaptation and a set of 123 putative candidate genes were identified. Moreover, all the C4 photosynthesis genes existed and were active in R. soongorica, which has been regarded as a typical C3 plant. CONCLUSION/SIGNIFICANCE: The assembled unigenes in present work provide abundant genomic information for the functional assignments in an extreme xerophyte R. soongorica, and will help us exploit the genetic basis of how desert plants adapt to drought environment in the near future.

  4. Screening the Drug Sensitivity Genes Related to GEM and CDDP in the Lung Cancer Cell-lines

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    Chunyu YANG

    2009-10-01

    Full Text Available Background and objective Screening of small-cell lung cancer (SCLC and non-small cell lung cancer (NSCLC cell lines with gemcitabine hydrochloride (GEM and cisplatin (CDDP related to drug sensitivity gene might clarify the action mechanism of anti-cancer drugs and provide a new clue for overcoming drug resistance and the development of new anti-cancer drugs, and also provide theoretical basis for the clinical treatment of individual. Methods The drug sensitivity of CDDP and GEM in 4 SCLC cell lines and 6 NSCLC cell lines was determined using MTT colorimetric assay, while the cDNA macroarray was applied to detect the gene expression state related to drug sensitivity of 10 lung cancer cell line in 1 291, and the correlation between the two was analysized. Results There were 6 genes showing significant positive correlation (r≥0.632, P < 0.05 with GEM sensitivity; 45 genes positively related to CDDP; another 41 genes related to both GEM and CDDP (r≥± 0.4. Lung cancer with GEM and CDDP sensitivity of two types of drugs significantly related genes were Metallothinein (Signal transduction molecules, Cathepsin B (Organization protease B and TIMP1 (Growth factor; the GEM, CDDP sensitivity associated genes of lung cancer cell lines mainly distributed in Metallothinein, Cathepsin B, growth factor TIMP1 categories. Conclusion There existed drug-related sensitive genes of GEM, CDDP in SCLC and NSCLC cell lines; of these genes, Metallothinein, Cathepsin B and TIMP1 genes presented a significant positive correlation with GEM drug sensitivity, a significant negative correlation with CDDP drug sensitivity.

  5. Kearns-Sayre syndrome with facial and white matter extensive involvement: a (mitochondrial and nuclear gene related? neurocristopathy?

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    Agostino Berio

    2017-12-01

    Full Text Available The Authors report on a patient with Kearns-Sayre syndrome, large mtDNA deletion (7/kb, facial abnormalities and severe central nervous system (CNS white matter radiological features, commonly attributed to spongy alterations. The common origin from neural crest cell (NCC of facial structures (cartilagineous, osseous, vascular and of the peripheral nervous system and of peripheral glia and partially of the CNS white matter are underlined and the facial and glial abnormalities are attributed to the abnormal reproduction/migration of NCC. In this view, the CNS spongy alterations in KSS may be not only a dystrophic process (leukodystrophy but also a dysplastic condition (leukodysplasia. The Authors hypothesize that the symptoms may be related to mtDNA mutations associated to NCC nuclear gene abnormality. SOX 10 gene may be a nuclear candidate gene, as reported in some case of Waardenburg IV syndrome.

  6. Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: the gender-specific differences.

    Science.gov (United States)

    Ubl, Philipp; Gincu, Tatiana; Keilani, Mohammad; Ponhold, Lothar; Crevenna, Richard; Niederle, Bruno; Hacker, Marcus; Li, Shuren

    2014-08-01

    The aim of this study was to compare the side effects of the pentagastrin test and the calcium stimulation test in patients with increased basal calcitonin concentration, especially the gender-specific differences of side effects. A total of 256 patients (123 females and 133 males, mean age of 56 ± 27 years, range 21-83 years) had both pentagastrin and calcium stimulation tests. All patients filled in a questionnaire regarding the side effects within 30 min after completion of the stimulation tests. The differences of side effects between female and male patients as well as between the pentagastrin stimulation test and the calcium stimulation test were evaluated. Warmth feeling was the most frequent occurring side effect in all patients who had both pentagastrin and calcium stimulation tests, followed by nausea, altered gustatory sensation, and dizziness. The incidences of urgency to micturate (p stimulation test. Significant higher incidences of urgency to micturate (p stimulation test as compared with those by pentagastrin test in female patients. The incidences of nausea (p stimulation test than by calcium stimulation test. There is a significant gender-specific difference in side effects induced by calcium stimulation test. Female patients have fewer side effects by pentagastrin test than by calcium stimulation test. Male patients may tolerate the calcium stimulation test better than the pentagastrin test.

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

    Science.gov (United States)

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

    2011-10-01

    This study investigates the combined effect of absorption enhancers and electrical assistance on transbuccal salmon calcitonin (sCT) delivery, using fresh swine buccal tissue. We placed 200 IU (40 μg/mL) of each sCT formulation--containing various concentrations of ethanol, N-acetyl-L-cysteine (NAC), and sodium deoxyglycocholate (SDGC)--onto the donor part of a Franz diffusion cell. Then, 0.5 mA/cm(2) of fixed anodal current was applied alone or combined with chemical enhancers. The amount of permeated sCT was analyzed using an ELISA kit, and biophysical changes of the buccal mucosa were investigated using FT-IR spectroscopy, and hematoxylin-eosin staining methods were used to evaluate histological alteration of the buccal tissues. The flux (J(s)) of sCT increased with the addition of absorption enhancer groups, but it was significantly enhanced by the application of anodal iontophoresis (ITP). FT-IR study revealed that all groups caused an increase in lipid fluidity but only the groups containing SDGC showed statistically significant difference. Although the histological data of SDGC groups showed a possibility for tissue damage, the present enhancing methods appear to be safe. In conclusion, the combination of absorption enhancers and electrical assistance is a potential strategy for the enhancement of transbuccal sCT delivery. Copyright © 2011 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2012-06-01

    Protein aggregation is a major instability that can occur during all stages of protein drug production and development. Protein aggregates may compromise the safety and efficacy of the final protein formulation. In this paper, various new excipients [phenylbutylamino-, benzyl-, and cholesteryl-polyethylene glycols (PEGs)] and their use for the reduction of aggregation of salmon calcitonin (sCT) and hen egg-white lysozyme (HEWL) by noncovalent PEGylation are presented. The ability to suppress aggregation of sCT in various buffer systems at a 1:1 molar ratio was assessed by following changes in protein conformation and aggregation state over time. The results are compared with that of dansyl- and L-tryptophan (Trp)-PEGs described in earlier publications. Furthermore, the influence of the different PEG-based excipients on the aggregation of HEWL was measured. HEWL aggregation was completely suppressed in the presence of cholesteryl-PEGs (2 and 5 kDa), whereas deterioration was observed using benzyl-methoxy polyethylene glycols (mPEGs; 2 and 5 kDa). Phenylbutylamino- and Trp-mPEG (2 kDa), as well as dansyl-PEGs of different molecular weight prolonged the lag phase of aggregation and reduced the aggregation velocity of HEWL. Copyright © 2012 Wiley Periodicals, Inc.

  9. Ghrelin improves vascular autophagy in rats with vascular calcification.

    Science.gov (United States)

    Xu, Mingming; Liu, Lin; Song, Chenfang; Chen, Wei; Gui, Shuyan

    2017-06-15

    This study aimed to investigate whether ghrelin ameliorated vascular calcification (VC) through improving autophagy. VC model was induced by nicotine plus vitamin D 3 in rats and β-glycerophosphate in vascular smooth muscle cell (VSMC). Calcium deposition was detected by von Kossa staining or alizarin red S staining. ALP activity was also detected. Western blot was used to assess the protein expression. Ghrelin treatment attenuated the elevation of calcium deposition and ALP activity in VC model both in vivo and in vitro. Interesting, the protein levels of autophagy markers, LC3 and beclin1 were significantly upregulated by ghrelin in VC model. An autophagy inhibitor, 3-methyladenine blocks the ameliorative effect of ghrelin on VC. Furthermore, protein expressions of phosphate-AMPK were increased by ghrelin treatment both in calcified aorta and VSMC. The effect of ghrelin on autophagy induction and VC attenuation was prevented by AMPK inhibitor, compound C. Our results suggested that ghrelin improved autophagy through AMPK activation, which was resulted in VC amelioration. These data maybe throw light on prevention and therapy of VC. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Vascular dementia: Facts and controversies

    Directory of Open Access Journals (Sweden)

    Pavlović Aleksandra

    2013-01-01

    Full Text Available Vascular dementia (VaD is the second most frequent dementia after Alzheimer’s disease, and is diagnosed during lifetime in 20% of demented patients. Five­year survival rate in VaD is 39%, while it is estimated to be 75% in healthy persons of the same age. It is therefore important to make correct diagnosis of VaD early in the course of the disease. Risk factors for VaD are identical to stroke risk factors, and there are significant possibilities for the prevention of vascular cognitive decline. Cognitive decline develops acutely or step­by­step within three months after stroke, but more gradual progression of intellectual decline is also possible. Neurological examination can reveal pyramidal and extrapyramidal signs, pseudobulbar palsy, gait disturbance and urinary incontinence. Neuropsychological profile comprises the loss of cognitive set shifting, decline in word fluency, verbal learning difficulties, perseverations, difficulties in complex figure copying, and in patients with cortically located lesions also problems with speech and praxia. The basis of the diagnosis is, besides history, neurological examination and neuropsychological assessment, computed tomography and/ or magnetic resonance brain imaging. Vascular risk factors control is the most important measure in VaD prevention. Modern guidelines for the treatment of cognitive decline in VaD emphasize that donepezil can be useful in the improvement of cognitive status at the level of Class IIa recommendation at the level of evidence A, while memantine may be useful in patients with mixed VaD and Alzheimer’s disease dementia. [Projekat Ministarstva nauke Republike Srbije, br. 175022 i br. 175033

  11. Non-vascular surgical mediastinum

    International Nuclear Information System (INIS)

    Schiavon, S.; Trenaghi, P.; Nardini, S.; Pagan, V.

    1989-01-01

    A review was made of the chest X-ray features of 120 patients who underwent surgical treatment for mediastinal non-vascular pathologies over the past 12 years in the Mestre Hospital. A method of analysis is proposed which takes into account not only the differences between the immediate post-operative period and the follow-up, but also the anatomotopographic partition and the surgical practice. Normal and pathological patterns for both of the above periods are described. The ''dimness'' of the arial tracheogram is emphasized as a usefull and early sign of mediastinal recurrence

  12. Vascular comorbidities in multiple sclerosis

    DEFF Research Database (Denmark)

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils

    2016-01-01

    To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry...... and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique...

  13. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    , the retinal vascular fractal dimension was measured using the box-counting method and compared within monozygotic and dizygotic twin pairs using Pearson correlation coefficients. Falconer's formula and quantitative genetic models were used to determine the genetic component of variation. Results: The mean...... fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0...

  14. NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

    Science.gov (United States)

    Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a

  15. Equine Chorionic Gonadotropin Modulates the Expression of Genes Related to the Structure and Function of the Bovine Corpus Luteum.

    Science.gov (United States)

    Sousa, Liza Margareth Medeiros de Carvalho; Mendes, Gabriela Pacheco; Campos, Danila Barreiro; Baruselli, Pietro Sampaio; Papa, Paula de Carvalho

    2016-01-01

    We hypothesized that stimulatory and superovulatory treatments, using equine chorionic gonadotropin (eCG), modulate the expression of genes related to insulin, cellular modelling and angiogenesis signaling pathways in the bovine corpus luteum (CL). Therefore, we investigated: 1-the effect of these treatments on circulating insulin and somatomedin C concentrations and on gene and protein expression of INSR, IGF1 and IGFR1, as well as other insulin signaling molecules; 2-the effects of eCG on gene and protein expression of INSR, IGF1, GLUT4 and NFKB1A in bovine luteal cells; and 3-the effect of stimulatory and superovulatory treatments on gene and protein expression of ANG, ANGPT1, NOS2, ADM, PRSS2, MMP9 and PLAU. Serum insulin did not differ among groups (P = 0.96). However, serum somatomedin C levels were higher in both stimulated and superovulated groups compared to the control (P = 0.01). In stimulated cows, lower expression of INSR mRNA and higher expression of NFKB1A mRNA and IGF1 protein were observed. In superovulated cows, lower INSR mRNA expression, but higher INSR protein expression and higher IGF1, IGFR1 and NFKB1A gene and protein expression were observed. Expression of angiogenesis and cellular modelling pathway-related factors were as follows: ANGPT1 and PLAU protein expression were higher and MMP9 gene and protein expression were lower in stimulated animals. In superovulated cows, ANGPT1 mRNA expression was higher and ANG mRNA expression was lower. PRSS2 gene and protein expression were lower in both stimulated and superovulated animals related to the control. In vitro, eCG stimulated luteal cells P4 production as well as INSR and GLUT4 protein expression. In summary, our results suggest that superovulatory treatment induced ovarian proliferative changes accompanied by increased expression of genes providing the CL more energy substrate, whereas stimulatory treatment increased lipogenic activity, angiogenesis and plasticity of the extracellular matrix

  16. Equine Chorionic Gonadotropin Modulates the Expression of Genes Related to the Structure and Function of the Bovine Corpus Luteum.

    Directory of Open Access Journals (Sweden)

    Liza Margareth Medeiros de Carvalho Sousa

    Full Text Available We hypothesized that stimulatory and superovulatory treatments, using equine chorionic gonadotropin (eCG, modulate the expression of genes related to insulin, cellular modelling and angiogenesis signaling pathways in the bovine corpus luteum (CL. Therefore, we investigated: 1-the effect of these treatments on circulating insulin and somatomedin C concentrations and on gene and protein expression of INSR, IGF1 and IGFR1, as well as other insulin signaling molecules; 2-the effects of eCG on gene and protein expression of INSR, IGF1, GLUT4 and NFKB1A in bovine luteal cells; and 3-the effect of stimulatory and superovulatory treatments on gene and protein expression of ANG, ANGPT1, NOS2, ADM, PRSS2, MMP9 and PLAU. Serum insulin did not differ among groups (P = 0.96. However, serum somatomedin C levels were higher in both stimulated and superovulated groups compared to the control (P = 0.01. In stimulated cows, lower expression of INSR mRNA and higher expression of NFKB1A mRNA and IGF1 protein were observed. In superovulated cows, lower INSR mRNA expression, but higher INSR protein expression and higher IGF1, IGFR1 and NFKB1A gene and protein expression were observed. Expression of angiogenesis and cellular modelling pathway-related factors were as follows: ANGPT1 and PLAU protein expression were higher and MMP9 gene and protein expression were lower in stimulated animals. In superovulated cows, ANGPT1 mRNA expression was higher and ANG mRNA expression was lower. PRSS2 gene and protein expression were lower in both stimulated and superovulated animals related to the control. In vitro, eCG stimulated luteal cells P4 production as well as INSR and GLUT4 protein expression. In summary, our results suggest that superovulatory treatment induced ovarian proliferative changes accompanied by increased expression of genes providing the CL more energy substrate, whereas stimulatory treatment increased lipogenic activity, angiogenesis and plasticity of the

  17. CIRSE Vascular Closure Device Registry

    International Nuclear Information System (INIS)

    Reekers, Jim A.; Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2011-01-01

    Purpose: Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods: The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results: Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0–14.5] for antegrade access and 1.8% (95% CI 1.1–2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only 5.9 cm, and two vessel occlusions. Conclusion: The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters.

  18. Neuroradiological findings in vascular dementia

    Energy Technology Data Exchange (ETDEWEB)

    Guermazi, Ali; Miaux, Yves; Suhy, Joyce; Pauls, Jon; Lopez, Ria [Synarc, Inc., Department of Radiology Services, San Francisco, CA (United States); Rovira-Canellas, Alex [Hospital General Universitari Vall d' Hebron, Unita de Resonancia Magnetica, Barcelona (Spain); Posner, Holly [Eisai, Inc., Teaneck, NJ (United States)

    2007-01-15

    There are multiple diagnostic criteria for vascular dementia (VaD) that may define different populations. Utilizing the criteria of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) has provided improved consistency in the diagnosis of VaD. The criteria include a table listing brain imaging lesions associated with VaD. The different neuroradiological aspects of the criteria are reviewed based on the imaging data from an ongoing large-scale clinical trial testing a new treatment for VaD. The NINDS-AIREN criteria were applied by a centralized imaging rater to determine eligibility for enrollment in 1,202 patients using brain CT or MRI. Based on the above data set, the neuroradiological features that are associated with VaD and that can result from cerebral small-vessel disease with extensive leukoencephalopathy or lacunae (basal ganglia or frontal white matter), or may be the consequence of single strategically located infarcts or multiple infarcts in large-vessel territories, are illustrated. These features may also be the consequence of global cerebral hypoperfusion, intracerebral hemorrhage, or other mechanisms such as genetically determined arteriopathies. Neuroimaging confirmation of cerebrovascular disease in VaD provides information about the topography and severity of vascular lesions. Neuroimaging may also assist with the differential diagnosis of dementia associated with normal pressure hydrocephalus, chronic subdural hematoma, arteriovenous malformation or tumoral diseases. (orig.)

  19. Diffuse and vascular hepatic diseases

    International Nuclear Information System (INIS)

    Kreimeyer, S.; Grenacher, L.

    2011-01-01

    In addition to focal liver lesions, diffuse and vascular disorders of the liver represent a wide spectrum of liver diseases which are from the radiological point of view often difficult or nearly impossible to diagnose. Classical diagnostic methods are computed tomography and magnetic resonance imaging in addition to ultrasound. Diffuse parenchymal damage caused by diseases of various etiologies is therefore difficult to evaluate because it often lacks characteristic morphological features. For hepatic steatosis, hemochromatosis/siderosis as an example of a diffuse storage disease and sarcoidosis and candidiasis as infectious/inflammatory diseases, an image-based diagnosis is appropriate in some cases. For most diffuse liver diseases, however only nonspecific changes are visualized. Vascular pathologies of the liver, such as the Budd-Chiari syndrome and portal vein thrombosis, however, can usually be diagnosed very clearly using radiology and there is also a very effective interventional radiological treatment. Chronic diseases very often culminate in liver cirrhosis which is highly associated with an increased risk of liver cancer. (orig.) [de

  20. CIRSE Vascular Closure Device Registry

    Science.gov (United States)

    Müller-Hülsbeck, Stefan; Libicher, Martin; Atar, Eli; Trentmann, Jens; Goffette, Pierre; Borggrefe, Jan; Zeleňák, Kamil; Hooijboer, Pieter; Belli, Anna-Maria

    2010-01-01

    Purpose Vascular closure devices are routinely used after many vascular interventional radiology procedures. However, there have been no major multicenter studies to assess the safety and effectiveness of the routine use of closure devices in interventional radiology. Methods The CIRSE registry of closure devices with an anchor and a plug started in January 2009 and ended in August 2009. A total of 1,107 patients were included in the registry. Results Deployment success was 97.2%. Deployment failure specified to access type was 8.8% [95% confidence interval (95% CI) 5.0–14.5] for antegrade access and 1.8% (95% CI 1.1–2.9) for retrograde access (P = 0.001). There was no difference in deployment failure related to local PVD at the access site. Calcification was a reason for deployment failure in only 5.9 cm, and two vessel occlusions. Conclusion The conclusion of this registry of closure devices with an anchor and a plug is that the use of this device in interventional radiology procedures is safe, with a low incidence of serious access site complications. There seems to be no difference in complications between antegrade and retrograde access and other parameters. PMID:20981425

  1. Enhanced Recovery after Vascular Surgery

    Directory of Open Access Journals (Sweden)

    Milena D. Stojanovic

    2018-01-01

    Full Text Available The beginnings of the enhanced recovery after surgery (ERAS program were first developed for patients in colorectal surgery, and after it was established as the standard of care in this surgical field, it began to be applied in many others surgical areas. This is multimodal, evidence-based approach program and includes simultaneous optimization of preoperative status of patients, adequate selection of surgical procedure and postoperative management. The aim of this program is to reduce complications, the length of hospital stay and to improve the patients outcome. Over the past decades, special attention was directed to the postoperative management in vascular surgery, especially after major vascular surgery because of the great risk of multiorgan failure, such as: respiratory failure, myocardial infarction, hemodynamic instability, coagulopathy, renal failure, neurological disorders, and intra-abdominal complications. Although a lot of effort was put into it, there is no unique acceptable program for ERAS in this surgical field, and there is still a need to point out the factors responsible for postoperative outcomes of these patients. So far, it is known that special attention should be paid to already existing diseases, type and the duration of the surgical intervention, hemodynamic and fluid management, nutrition, pain management, and early mobilization of patients.

  2. Vascular access for home haemodialysis.

    Science.gov (United States)

    Al Shakarchi, Julien; Day, C; Inston, N

    2018-03-01

    Home haemodialysis has been advocated due to improved quality of life. However, there are very little data on the optimum vascular access for it. A retrospective cohort study was carried on all patients who initiated home haemodialysis between 2011 and 2016 at a large university hospital. Access-related hospital admissions and interventions were used as primary outcome measures. Our cohort consisted of 74 patients. On initiation of home haemodialysis, 62 individuals were using an arteriovenous fistula as vascular access, while the remaining were on a tunnelled dialysis catheter. Of the 12 patients who started on a tunnelled dialysis catheter, 5 were subsequently converted to either an arteriovenous fistula ( n = 4) or an arteriovenous graft ( n = 1). During the period of home haemodialysis use, four arteriovenous fistula failed or thrombosed with patients continuing on home haemodialysis using an arteriovenous graft ( n = 3) or a tunnelled dialysis catheter ( n = 1). To maintain uninterrupted home haemodialysis, interventional rates were 0.32 per arteriovenous fistula/arteriovenous graft access-year and 0.4 per tunnelled dialysis catheter access-year. Hospital admission rates for patients on home haemodialysis were 0.33 per patient-year. Our study has shown that home haemodialysis can be safely and independently performed at home within a closely managed home haemodialysis programme. The authors also advocate the use of arteriovenous fistulas for this cohort of patients due to both low complication and intervention rates.

  3. Vascular emergencies in liver trauma

    Energy Technology Data Exchange (ETDEWEB)

    Taourel, P. [Centre Hospitalier Universitaire Lapeyronie, Montpellier (France)], E-mail: p-taourel@chu-montpellier.fr; Vernhet, H. [Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier (France); Suau, A.; Granier, C. [Centre Hospitalier Universitaire Lapeyronie, Montpellier (France); Lopez, F.M. [Centre Hospitalier Universitaire, Nimes (France); Aufort, S. [Centre Hospitalier Universitaire Lapeyronie, Montpellier (France)

    2007-10-15

    The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of compli cation and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications.

  4. Vascular emergencies in liver trauma

    International Nuclear Information System (INIS)

    Taourel, P.; Vernhet, H.; Suau, A.; Granier, C.; Lopez, F.M.; Aufort, S.

    2007-01-01

    The use of CT in the diagnosis and management of liver trauma is responsible for the shift from routine surgical versus non-surgical treatment in the management of traumatic liver injuries, even when they are of high grade. The main cause of compli cation and of death in liver trauma is related to vascular injury. The goal of this review focussed on the vascular complications of liver trauma is to describe the elementary lesions shown by CT in liver trauma including laceration, parenchymal hematoma and contusions, partial devascularisation, subcapsular hematomas, hemoperitoneum, active bleeding, pseudoaneurysm of the hepatic artery, bile leak, and periportal oedema, to illustrate the possible pitfalls in CT diagnosis of liver trauma and to underline the key-points which may absolutely be present in a CT report of liver trauma. Then we will remind the grading system based on the CT features and we will analyze the interest and limitations of such grading systems. Last we will discuss the diagnostic strategy at the early phase in patients with suspected liver trauma according to their clinical conditions and underline the conditions of arterial embolization, and then we will discuss the diagnosis strategy at the delayed phase according to the suspected complications

  5. Vascularized bone transplant chimerism mediated by vascular endothelial growth factor.

    Science.gov (United States)

    Willems, Wouter F; Larsen, Mikko; Friedrich, Patricia F; Bishop, Allen T

    2015-01-01

    Vascular endothelial growth factor (VEGF) induces angiogenesis and osteogenesis in bone allotransplants. We aim to determine whether bone remodeling in VEGF-treated bone allotransplants results from repopulation with circulation-derived autogenous cells or survival of allogenic transplant-derived cells. Vascularized femoral bone transplants were transplanted from female Dark Agouti rats (DA;RT1(a) ) to male Piebald Viral Glaxo (PVG;RT1(c) ). Arteriovenous bundle implantation and short-term immunosuppression were used to maintain cellular viability. VEGF was encapsulated in biodegradable microspheres and delivered intramedullary in the experimental group (n = 22). In the control group (n = 22), no VEGF was delivered. Rats were sacrificed at 4 or 18 weeks. Laser capture microdissection of bone remodeling areas was performed at the inner and outer cortex. Sex-mismatched genes were quantified with reverse transcription-polymerase chain reaction to determine the amount of male cells to total cells, defined as the relative expression ratio (rER). At 4 weeks, rER was significantly higher at the inner cortex in VEGF-treated transplants as compared to untreated transplants (0.622 ± 0.225 vs. 0.362 ± 0.081, P = 0.043). At 4 weeks, the outer cortex in the control group had a significantly higher rER (P = 0.038), whereas in the VEGF group, the inner cortex had a higher rER (P = 0.015). Over time, in the outer cortex the rER significantly increased to 0.634 ± 0.106 at 18 weeks in VEGF-treated rats (P = 0.049). At 18 weeks, the rER was >0.5 at all cortical areas in both groups. These in vivo findings suggest a chemotactic effect of intramedullary applied VEGF on recipient-derived bone and could imply that more rapid angiogenesis of vascularized allotransplants can be established with microencapsulated VEGF. © 2014 Wiley Periodicals, Inc.

  6. Proatherogenic pathways leading to vascular calcification

    International Nuclear Information System (INIS)

    Mazzini, Michael J.; Schulze, P. Christian

    2006-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the western world and atherosclerosis is the major common underlying disease. The pathogenesis of atherosclerosis involves local vascular injury, inflammation and oxidative stress as well as vascular calcification. Vascular calcification has long been regarded as a degenerative process leading to mineral deposition in the vascular wall characteristic for late stages of atherosclerosis. However, recent studies identified vascular calcification in early stages of atherosclerosis and its occurrence has been linked to clinical events in patients with cardiovascular disease. Its degree correlates with local vascular inflammation and with the overall impact and the progression of atherosclerosis. Over the last decade, diverse and highly regulated molecular signaling cascades controlling vascular calcification have been described. Local and circulating molecules such as osteopontin, osteoprogerin, leptin and matrix Gla protein were identified as critical regulators of vascular calcification. We here review the current knowledge on molecular pathways of vascular calcification and their relevance for the progression of cardiovascular disease

  7. World Federation of Vascular Societies: presidential address

    DEFF Research Database (Denmark)

    Sillesen, Henrik Hegaard

    2010-01-01

    The presidential address describes briefly the history of the World Federation for Vascular Societies (WFVS) and its objectives. Vascular Surgery today includes interventional procedures (open surgical and endovascular) in addition to risk factor reduction and medical treatment. It is equally imp...... throughout the world. In addition, for introduction of new treatments, training issues and dissemination of science a global organisation like the WFVS is needed.......The presidential address describes briefly the history of the World Federation for Vascular Societies (WFVS) and its objectives. Vascular Surgery today includes interventional procedures (open surgical and endovascular) in addition to risk factor reduction and medical treatment. It is equally...

  8. Identification and tissue distribution of mRNAs encoding salmon-type calcitonins-IV and -V in the rainbow trout.

    Science.gov (United States)

    Hidaka, Yoshie; Suzuki, Masakazu

    2004-06-01

    Four types of calcitonin are produced in salmonid fish, although their functional diversity is almost unknown. To explore the significance of these isoforms, we have characterized salmon-type calcitonin (sCT) mRNAs in the rainbow trout (Oncorhynchus mykiss), and examined their tissue distribution. In addition to the previously isolated sCT-I cDNAs, two new forms of sCT cDNA were cloned from the ultimobranchial gland, and one of them (sCT-IV cDNA) was predicted to encode an N-terminal peptide of 80 amino acid residues, a putative cleavage site Lys-Arg, sCT-IV, a cleavage and amidation sequence Gly-Lys-Lys-Arg, and a C-terminal peptide of 18 amino acids. The sCT-IV precursor was 78% identical with the rainbow trout sCT-I precursors. The other cloned cDNA encoded a precursor for a novel CT, sCT-V. The sCT-V peptide was different from sCT-IV by only one amino acid residue: Val at position 8 in the latter was replaced by Met. The sCT-V precursor had 80 and 90% identity with the sCT-I and -IV precursors respectively. No cDNA clones were obtained for sCTs-II or -III.Tissue distribution of sCT-I, -IV and -V mRNAs was examined by RT-PCR and specific cleavage with restriction enzymes. An amplified fragment from sCT-I mRNA was detected not only in the ultimobranchial gland, but also in the gills, testis and ovary. RT-PCR analysis coupled to restriction digestion further revealed that sCT-IV mRNA was expressed in both the testis and the ultimobranchial gland. The expression sites of sCT-IV mRNA were localized to the Leydig cells of the testis and to the parenchymal cells of the ultimobranchial gland, by in situ hybridization histochemistry. Although the amino acid sequence of sCT-V peptide was nearly the same as that of sCT-IV, the sCT-V gene showed a much wider pattern of expression: the band amplified by RT-PCR was detected in all the tissues examined except the kidney, gills and blood cells. The sCT-V mRNA was shown to be localized in the parenchymal cells of the

  9. Calcitonin receptor gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis in South Indian population – An observational study

    Directory of Open Access Journals (Sweden)

    Anuradha Ankam

    2017-01-01

    Full Text Available Context: Chronic periodontitis and osteoporosis are multifactorial diseases which share common risk factors. Interactions between genetic and other factors determine the likely hood of osteoporotic fractures and chronic periodontitis. Calcitonin receptor (CTR gene polymorphism is one of the important factors which contribute to the development of osteoporosis and chronic periodontitis. Aims: This study highlights the association of CTR gene polymorphisms at codon 447 in patients with osteoporosis and chronic periodontitis and healthy controls in south Indian population. Settings and Design: The study was designed as a case–control retrospective, observational clinical trial which was conducted to assess the role of CTR gene polymorphism in patients with osteoporosis and periodontitis as well as in healthy controls. Materials and Methods: A total of 50 subjects were taken into the study comprising of 20 healthy and 30 osteoporotic subjects with chronic periodontitis between the age group of 30–55 years. Within the limitations of our study, only 50 subjects were taken in the study due to the strict sampling method (Patients who were just diagnosed with osteoporosis and periodontitis and hence not taking any medication. 2 ml of blood sample was collected in ethylenediamine tetra acetic acid containing vials, and polymerase chain reaction was run to identify CTR gene polymorphism. Statistical Analysis Used: Statistical analysis was done by student t-test. Pertaining to C > T allele pattern there was a significant difference between the test and control group. Results: A significant difference was observed between the test and control group in relation to the C > T allele pattern. Patients showing TT genotype distribution had greater periodontal destruction and lower bone-mineral density compared to CT genotype distribution followed by CC genotype distribution indicating TT homozygotes are more prone to the development of osteoporosis with

  10. Basal Serum Calcitonin, After Calcium Stimulation, and in the Needle Washout of Patients with Thyroid Nodules and Mild or Moderate Basal Hypercalcitoninemia.

    Science.gov (United States)

    Rosario, P W; Calsolari, M R

    2017-02-01

    This prospective study evaluated the concentrations of basal serum calcitonin (Ctn), Ctn after stimulation with calcium, and Ctn in the needle washout (FNA-Ctn) as predictors of sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules and basal Ctn between 10 and 100 pg/ml. Forty-one patients were included in the study. MTC was diagnosed in only 6 patients (14.6%). None of the patients with basal Ctn≤24.6 pg/ml (n=26) or stimulated Ctn≤186.5 pg/ml (n=21) had MTC. All patients without MTC had basal Ctnstimulated Ctnbasal Ctn between 24.6 and 47 pg/ml (n=12), 3 (25%) had MTC. Among patients with stimulated Ctn between 186.5 and 655.2 pg/ml (n=18), 4 (22.2%) had MTC. FNA-Ctn distinguished nodules that were MTC (n=6) from those that were not (n=60), without overlapping results. In the calcium stimulation test, 19 patients (46.3%) reported some adverse effect, but none of them was severe or required specific treatment. Our results highlight that in patients without a history suspicious for MTC, mild or moderate basal hypercalcitoninemia should not establish the diagnosis of this tumor. Depending on the concentration found, basal Ctn should be sufficient to define patient management. In doubtful cases, FNA-Ctn seems to be the best diagnostic test. Calcium stimulation testing was safe, but more studies are needed to determine the Ctn cutoff after stimulation with calcium. © Georg Thieme Verlag KG Stuttgart · New York.

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

    Directory of Open Access Journals (Sweden)

    Hiraku Onishi

    2016-09-01

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

  12. Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats.

    Science.gov (United States)

    Feigh, Michael; Andreassen, Kim V; Hjuler, Sara T; Nielsen, Rasmus H; Christiansen, Claus; Henriksen, Kim; Karsdal, Morten A

    2013-07-01

    Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects of oral sCT on energy and glucose homeostasis in high-fat diet (HFD)- and ovariectomy (OVX)-induced obese rats. Furthermore, the weight-regulatory and gluco-regulatory effects of short-term oral sCT intervention on HFD-induced obese rats were explored. For prevention, female rats exposed to HFD with or without OVX were treated with oral sCT for 5 weeks. As intervention, HFD-induced obese male rats were treated with oral sCT for 4 days. Body weight, food intake, and plasma glucose, insulin, and leptin levels were measured, and the clinical homeostasis model assessment for insulin resistance (HOMA-IR) index was calculated. In addition, oral glucose tolerance was evaluated in the systemic and portal circulations. For prevention, oral sCT reduced body weight by ∼16% to 19% (P fasting glycemia (P obesity. Furthermore, oral sCT significantly reduced the incremental area under the curve for plasma glucose and insulin by ∼40% and ∼70%, respectively, during glucose tolerance testing. As intervention in HFD-induced obese rats, oral sCT reduced body weight, fasting glycemia, and insulinemia in conjunction with HOMA-IR (P obese rats, indicating the clinical usefulness of oral sCT in postmenopausal obesity-related IR and type 2 diabetes.

  13. 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.

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

    Science.gov (United States)

    2013-01-01

    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. PMID:23421519

  15. Calcitonin assay in wash-out fluid after fine-needle aspiration biopsy in patients with a thyroid nodule and border-line value of the hormone.

    Science.gov (United States)

    Massaro, F; Dolcino, M; Degrandi, R; Ferone, D; Mussap, M; Minuto, F; Giusti, M

    2009-04-01

    Assaying calcitonin (CT) in the wash-out fluid from fine-needle aspiration biopsies (CT-FNAB) could be useful in the diagnosis of medullary thyroid carcinoma (MTC). The aim of this study was to correlate serum CT with cytology and CT-FNAB. Twenty-seven subjects (age range 27-75 yr) were studied. FNAB was performed in a thyroid nodule (no.=16) or lymph-node (no.=1 previously operated on for MTC) or in the prevalent nodule of multinodular goiters (no.=10). CT-FNAB values obtained in 37 subjects with normal serum CT (thyroid nodules served as a negative control. In these subjects, CTFNAB values were 8.2+/-6.4 ng/l (range 2-30 ng/l). In patients with a thyroid nodule under evaluation for MTC, serum CT and CT-FNAB values were 14.5+/-3.9 ng/l (range 10-24 ng/l) and 16.4+/-29.8 ng/l (range 2-144 ng/l), respectively. In 4 patients, CT-FNAB values were higher than the highest values found in our negative controls (30 ng/l), but cytology results were compatible with a benign thyroid lesion and pentagastrin testing was negative. In 3 cases with CT-FNAB 100 ng/l. Our data do not show any correlation between CT-FNAB and serum CT. In conclusion, borderline CT values in patients with thyroid nodules are not rare. Our experience suggests that CT-FNAB does not have the same importance as that reported in the literature for thyroglobulin and PTH assay in wash-out fluid after FNAB in malignant thyroid and hyperfunctioning parathyroid lesions.

  16. 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.

  17. [Immunologic problems in vascular homografts].

    Science.gov (United States)

    D'Addato, M; Mirelli, M

    2001-01-01

    Fresh arterial homografts are immunogenic, inducing in recipient a strong immune response specifically directed against the antigens of the donor graft. The initial immune response seems to be cellular (lymphocytotoxic) and the late reaction humoral (antibody), even if they are strictly correlated. Immunosuppressive therapy reduce the immune reaction, but this response is dose-related. Implanted arterial homografts induce a donor-specific response similar to chronic reaction, which occurs in the recipients of vascularized solid-organ allografts. Therefore, in arterial transplantation, ABO compatibility and negative crossmatch should be respected. Effort should be made to curb the immune response by prospective cross-matching, immunosuppressive therapy and preoperative manipulation of homografts to reduce their antigenicity.

  18. Heritability of Retinal Vascular Fractals

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Broe, Rebecca; Kessel, Line

    2017-01-01

    Purpose: To determine the genetic contribution to the pattern of retinal vascular branching expressed by its fractal dimension. Methods: This was a cross-sectional study of 50 monozygotic and 49 dizygotic, same-sex twin pairs aged 20 to 46 years. In 50°, disc-centered fundus photographs, the reti...... fractal dimension did not differ statistically significantly between monozygotic and dizygotic twin pairs (1.505 vs. 1.495, P = 0.06), supporting that the study population was suitable for quantitative analysis of heritability. The intrapair correlation was markedly higher (0.505, P = 0.......0002) in monozygotic twins than in dizygotic twins (0.108, P = 0.46), corresponding to a heritability h2 for the fractal dimension of 0.79. In quantitative genetic models, dominant genetic effects explained 54% of the variation and 46% was individually environmentally determined. Conclusions: In young adult twins...

  19. Vascular anastomosis by Argon Laser

    International Nuclear Information System (INIS)

    Gomes, O.M.; Macruz, R.; Armelin, E.; Brum, J.M.G.; Ribeiro, M.P.; Mnitentog, J.; Verginelli, G.; Pileggi, F.; Zerbini, E.J.

    1982-01-01

    Twenty four mongrel dogs, wheighing 13 to 24 kilograms were studied. After anesthesia, intubation and controlled ventilation, they were submitted to three types of vascular anastomosis: Group I - eight dogs with saphenous vein inter-carotid arteries by-pass: Group II - eight dogs with left mammary artery - left anterior descending coronary artery by-pass; Group III - eight dogs with venovenous anastomosis. In all groups 0.8 to 15 watts of Argon Laser power was applied to a total time of 90 to 300 seconds. The lower power for venovenous anastomosis and the greater for the arterial ones. The mean valves of resistence of the Laser anastomosis to pressure induced rupture was 730 mmHg in the immediate post operative study, and superior to 2.500 mmHg 30 days after. No signs of occlusion was demonstrated at the anastomosis sites by the angiographic and anathomo-patological study performed. (Author) [pt

  20. Vascular targeting with peptide libraries

    Energy Technology Data Exchange (ETDEWEB)

    Pasqualini, R. [La Jolla Cancer Research Center The Burnham Inst., La Jolla CA (United States)

    1999-06-01

    The authors have developed an 'in vivo' selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, they have isolate several organ and tumor-homing peptides. They have shown that each of those peptides binds of different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are up regulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animals models decrease toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angio genesis and lead to advances to extend the potential for targeting of drugs, genes and radionuclides in the context of many diseases.

  1. Vascular Morphodynamics During Secondary Growth.

    Science.gov (United States)

    de Reuille, Pierre Barbier; Ragni, Laura

    2017-01-01

    Quantification of vascular morphodynamics during secondary growth has been hampered by the scale of the process. Even in the tiny model plant Arabidopsis thaliana, the xylem can include more than 2000 cells in a single cross section, rendering manual counting impractical. Moreover, due to its deep location, xylem is an inaccessible tissue, limiting live imaging. A novel method to visualize and measure secondary growth progression has been proposed: "the Quantitative Histology" approach. This method is based on a detailed anatomical atlas, and image segmentation coupled with machine learning to automatically extract cell shapes and identify cell type. Here we present a new version of this approach, with a user-friendly interface implemented in the open source software LithoGraphX.

  2. Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

    NARCIS (Netherlands)

    Kanhai, D.A.N.I.S.

    2013-01-01

    Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society,

  3. FPGA controlled artificial vascular system

    Directory of Open Access Journals (Sweden)

    Laqua D.

    2015-09-01

    Full Text Available Monitoring the oxygen saturation of an unborn child is an invasive procedure, so far. Transabdominal fetal pulse oximetry is a promising method under research, used to estimate the oxygen saturation of a fetus noninvasively. Due to the nature of the method, the fetal information needs to be extracted from a mixed signal. To properly evaluate signal processing algorithms, a phantom modeling fetal and maternal blood circuits and tissue layers is necessary. This paper presents an improved hardware concept for an artificial vascular system, utilizing an FPGA based CompactRIO System from National Instruments. The experimental model to simulate the maternal and fetal blood pressure curve consists of two identical hydraulic circuits. Each of these circuits consists of a pre-pressure system and an artificial vascular system. Pulse curves are generated by proportional valves, separating these two systems. The dilation of the fetal and maternal artificial vessels in tissue substitutes is measured by transmissive and reflective photoplethysmography. The measurement results from the pressure sensors and the transmissive optical sensors are visualized to show the functionality of the pulse generating systems. The trigger frequency for the maternal valve was set to 1 per second, the fetal valve was actuated at 0.7 per second for validation. The reflective curve, capturing pulsations of the fetal and maternal circuit, was obtained with a high power LED (905 nm as light source. The results show that the system generates pulse curves, similar to its physiological equivalent. Further, the acquired reflective optical signal is modulated by the alternating diameter of the tubes of both circuits, allowing for tests of signal processing algorithms.

  4. Dynamics of nephron-vascular network

    DEFF Research Database (Denmark)

    Postnov, Dmitry; Postnov, D E; Marsh, D J

    2012-01-01

    The paper presents a modeling study of the spatial dynamics of a nephro-vascular network consisting of individual nephrons connected via a tree-like vascular branching structure. We focus on the effects of nonlinear mechanisms that are responsible for the formation of synchronous patterns in order...

  5. Imaging of the peripheral vascular system

    International Nuclear Information System (INIS)

    Gould, S.A.; Pond, G.D.; Pinsky, S.; Moss, G.S.; Srikantaswamy, S.; Ryo, U.Y.

    1984-01-01

    This book is limited neither to the peripheral vascular system nor to diagnostic imaging techniques. Its 18 chapters cover nonimaging blood-flow techniques (Doppler ultrasound, plethysmography) as well as noninvasive and invasive imaging techniques (ultrasound, computed tomography, radionuclide digital-subtraction angiography, and contrast angiography). These are applied not only to the peripheral vascular system but also to the aorta and vena cava

  6. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  7. Reconstructive vascular surgery below the knee

    DEFF Research Database (Denmark)

    Rasmussen, L B; Jelnes, R; Sager, P

    1986-01-01

    In a series of 38 consecutive patients with advanced peripheral vascular disease (i.e. rest pain) reconstructive vascular surgery was performed with the distal anastomosis below the knee. Ankle/arm pressure index (AAI) was 0.28 (0.11-0.47) preoperatively; accumulated graft patency rate was 0.47 (SD...

  8. Vascular dementia | Connor | African Journal of Psychiatry

    African Journals Online (AJOL)

    Vascular dementia (VaD) is a common but heterogeneous condition in which there is a clear temporal relationship between the dementia and vascular disease. It may result from multiple large or small vessel strokes or a single strategic stroke. Subcortical ischaemic VaD includes multiple lacunes and subcortical ...

  9. PanVascular medicine. 2. ed.

    Energy Technology Data Exchange (ETDEWEB)

    Lanzer, Peter (ed.) [Health Care Center Bitterfeld (Germany). Division of Cardiovascular Disease

    2015-06-01

    Vascular management and care has become a truly multidisciplinary enterprise as the number of specialists involved in the treatment of patients with vascular diseases has steadily increased. While in the past, treatments were delivered by individual specialists, in the twenty-first century a team approach is without doubt the most effective strategy. In order to promote professional excellence in this dynamic and rapidly evolving field, a shared knowledge base and interdisciplinary standards need to be established. Pan Vascular Medicine, 2nd edition has been designed to offer such an interdisciplinary platform, providing vascular specialists with state-of-the art descriptive and procedural knowledge. Basic science, diagnostics, and therapy are all comprehensively covered. In a series of succinct, clearly written chapters, renowned specialists introduce and comment on the current international guidelines and present up-to-date reviews of all aspects of vascular care.

  10. Using Polymeric Scaffolds for Vascular Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Alida Abruzzo

    2014-01-01

    Full Text Available With the high occurrence of cardiovascular disease and increasing numbers of patients requiring vascular access, there is a significant need for small-diameter (<6 mm inner diameter vascular graft that can provide long-term patency. Despite the technological improvements, restenosis and graft thrombosis continue to hamper the success of the implants. Vascular tissue engineering is a new field that has undergone enormous growth over the last decade and has proposed valid solutions for blood vessels repair. The goal of vascular tissue engineering is to produce neovessels and neoorgan tissue from autologous cells using a biodegradable polymer as a scaffold. The most important advantage of tissue-engineered implants is that these tissues can grow, remodel, rebuild, and respond to injury. This review describes the development of polymeric materials over the years and current tissue engineering strategies for the improvement of vascular conduits.

  11. Postoperative radiographic evaluation of vascularized fibular grafts

    International Nuclear Information System (INIS)

    Manaster, B.J.; Coleman, D.A.; Bell, D.A.

    1989-01-01

    This paper reports on thirty-five patients with free vascularized fibular grafts examined postoperatively with plain radiography. Early graft incorporation is seen as a fuzziness of the cortex at the site of its insertion into the host bone. Causes of failure in grafting for bone defects include graft fracture, hardware failure, and infection. A high percentage of complications or at least delayed unions occurred when vascularized fibular grafts were used to fill defects in the lower extremity. Conversely, upper extremity defects bridged by vascularized grafts heal quickly and hypertrophy. Vascularized grafts placed in the femoral head and neck for a vascular necrosis incorporate early on their superior aspect. The osseous tunnel in which they are placed is normally wider than the graft and often becomes sclerotic; this appearance does not represent nonunion

  12. PanVascular medicine. 2. ed.

    International Nuclear Information System (INIS)

    Lanzer, Peter

    2015-01-01

    Vascular management and care has become a truly multidisciplinary enterprise as the number of specialists involved in the treatment of patients with vascular diseases has steadily increased. While in the past, treatments were delivered by individual specialists, in the twenty-first century a team approach is without doubt the most effective strategy. In order to promote professional excellence in this dynamic and rapidly evolving field, a shared knowledge base and interdisciplinary standards need to be established. Pan Vascular Medicine, 2nd edition has been designed to offer such an interdisciplinary platform, providing vascular specialists with state-of-the art descriptive and procedural knowledge. Basic science, diagnostics, and therapy are all comprehensively covered. In a series of succinct, clearly written chapters, renowned specialists introduce and comment on the current international guidelines and present up-to-date reviews of all aspects of vascular care.

  13. GRECOS project. The use of genetics to predict the vascular recurrence after stroke

    Science.gov (United States)

    Fernández-Cadenas, Israel; Mendióroz, Maite; Giralt, Dolors; Nafria, Cristina; Garcia, Elena; Carrera, Caty; Gallego-Fabrega, Cristina; Domingues-Montanari, Sophie; Delgado, Pilar; Ribó, Marc; Castellanos, Mar; Martínez, Sergi; Freijo, Mari Mar; Jiménez-Conde, Jordi; Rubiera, Marta; Alvarez-Sabín, José; Molina, Carlos A.; Font, Maria Angels; Olivares, Marta Grau; Palomeras, Ernest; de la Ossa, Natalia Perez; Martinez-Zabaleta, Maite; Masjuan, Jaime; Moniche, Francisco; Canovas, David; Piñana, Carlos; Purroy, Francisco; Cocho, Dolores; Navas, Inma; Tejero, Carlos; Aymerich, Nuria; Cullell, Natalia; Muiño, Elena; Serena, Joaquín; Rubio, Francisco; Davalos, Antoni; Roquer, Jaume; Arenillas, Juan Francisco; Martí-Fábregas, Joan; Keene, Keith; Chen, Wei-Min; Worrall, Bradford; Sale, Michele; Arboix, Adrià; Krupinski, Jerzy; Montaner, Joan

    2017-01-01

    Background and Purpose Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack (TIA). Clinical scores do not predict the whole vascular recurrence risk, therefore we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. Methods We analyzed 256 polymorphisms from 115 candidate genes in three patient cohorts comprising 4,482 IS or TIA patients. The discovery cohort was prospectively recruited and included 1,494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2,988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score), and generated risk groups using a classification tree method. Results The analyses revealed that rs1800801 in the MGP gene (HR: 1.33, p= 9×10−03), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305), however it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS (p= 3.2×10−09) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared to previous SPI-II score (p=0.03). Conclusions The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population. PMID:28411264

  14. Using NASA's GeneLab for VESGEN Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways

    Science.gov (United States)

    Parsons-Wingerter, P.; Weitzel, Alexander; Vyas, R. J.; Murray, M. C.; Vickerman, M. B.; Bhattacharya, S.; Wyatt, S. E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. A unifying perspective is that vascular patterning offers a useful readout of molecular signaling that necessarily integrates these complex pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascularrelated changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the spatial and dynamic dimensions of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions. Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by

  15. [Gastric vascular lesions in cirrhosis: gastropathy and antral vascular ectasia].

    Science.gov (United States)

    Casas, Meritxell; Calvet, Xavier; Vergara, Mercedes; Bella, Maria Rosa; Junquera, Félix; Martinez-Bauer, Eva; Campo, Rafael

    2015-02-01

    Portal hypertensive gastropathy (GHP) is a complication of portal hypertension usually associated with liver cirrhosis. The pathogenesis is unclear but the presence of portal hypertension is an essential factor for its development. GHP may be asymptomatic or present as gastrointestinal bleeding or iron deficiency anemia. Endoscopic lesions vary from a mosaic pattern to diffuse red spots; the most common location is the fundus. Treatment is indicated when there is acute or chronic bleeding, as secondary prophylaxis. There is insufficient evidence to recommend primary prophylaxis in patients who have never bled. Drugs that decrease portal pressure, such as non-cardioselective beta-blockers, and/or endoscopic ablative treatments, such as argon-beam coagulation, may be used. The role of transarterial intrahepatic portosystemic shunt) or bypass surgery has been insufficiently analyzed. Antral vascular ectasia (EVA) is a rare entity in liver cirrhosis, whose pathophysiology is still unknown. Clinical presentation is similar to that of GHP and endoscopy usually shows red spots in the antrum. Biopsy is often required to differentiate EVA from GHP. There is no effective medical therapy, so endoscopic ablative therapy and, in severe cases, antrectomy are recommended. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  16. Vascular elastic photoacoustic tomography in humans

    Science.gov (United States)

    Hai, Pengfei; Zhou, Yong; Liang, Jinyang; Li, Chiye; Wang, Lihong V.

    2016-03-01

    Quantification of vascular elasticity can help detect thrombosis and prevent life-threatening conditions such as acute myocardial infarction or stroke. Here, we propose vascular elastic photoacoustic tomography (VE-PAT) to measure vascular elasticity in humans. VE-PAT was developed by incorporating a linear-array-based photoacoustic computed tomography system with a customized compression stage. By measuring the deformation of blood vessels under uniaxial loading, VE-PAT was able to quantify the vascular compliance. We first demonstrated the feasibility of VE-PAT in blood vessel phantoms. In large vessel phantoms, VE-PAT detected a decrease in vascular compliance due to simulated thrombosis, which was validated by a standard compression test. In small blood vessel phantoms embedded 3 mm deep in gelatin, VE-PAT detected elasticity changes at depths that are difficult to image using other elasticity imaging techniques. We then applied VE-PAT to assess vascular compliance in a human subject and detected a decrease in vascular compliance when an occlusion occurred downstream from the measurement point, demonstrating the potential of VE-PAT in clinical applications such as detection of deep venous thrombosis.

  17. [A new specialty is born: Vascular medicine].

    Science.gov (United States)

    Laroche, J-P

    2016-05-01

    On the 4th of December 2015, the French authorities officially recognized the birth of a specialty in vascular medicine entitled CO-DES cardiology-vascular/vascular Medicine. France is the 7th country to obtain this specialty after Switzerland, Germany, Austria, Czech Republic, Slovakia and Slovenia, six countries in the EEC. It has taken years to achieve a long but exciting experience: we went from hopes to disappointments, sometimes with the blues, but lobbying helping… with sustained confidence. This article tells the story of 30 years of struggle to achieve this vascular medicine specialty. Gaston Bachelard wrote: "Nothing is obvious, nothing is given, all is built." For the construction of vascular medicine, we had to overcome many obstacles, nothing was given to us, everything was conquered. Beware "The specialist is one who knows more and more things about an increasingly restricted field, up to 'knowing everything about nothing"' recalled Ralph Barton Ferry, philosopher; so there is room for modesty and humility but also convictions. The physical examination will remain the basis of our exercise. But let us recall the contributions of all those vascular physicians who practiced in the past, together with those currently active, who built day after day, year after year, a vascular medicine of quality. It is because of the trust of our colleagues and our patients that we can occupy the place that is ours today. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Diagnosis and management of vascular diseases

    International Nuclear Information System (INIS)

    Fan Xindong; Zheng Lianzhou

    2011-01-01

    Vascular disorders mainly include hemangiomas and vascular malformations, and constitute some of the most difficult diagnostic and therapeutic enigmas that can be encountered in the clinical practice. The clinical presentations are extremely variable and can range from an asymptomatic birthmark to life-threatening congestive heart failure. Attributing any of these extremely varied symptoms that a patients may present with to a vascular malformation may be a challenge to the most experienced clinical. This problem is compounded by the extreme rarity of these vascular lesions. If a clinician meets such a patient once every few years, it will be extremely difficult for the physicians to gain a steep learning curve. In such circumstances, it is difficult to formulate a standard of diagnosis and treatment for these vascular disorders. This paper aims to make a comprehensive and detailed description of the classification and diagnosis of the vascular disorders, the common used embolization agents, the concepts of interventional diagnosis and management and the therapies of various hemangiomas and vascular malformations. (authors)

  19. Vascular inflammatory cells in hypertension

    Directory of Open Access Journals (Sweden)

    David G. Harrison

    2012-05-01

    Full Text Available Hypertension is a common disorder with uncertain etiology. In the last several years, it has become evident that components of both the innate and adaptive immune system play an essential role in hypertension. Macrophages and T cells accumulate in the perivascular fat, the heart and the kidney of hypertensive patients and in animals with experimental hypertension. Various immunosuppressive agents lower blood pressure and prevent end-organ damage. Mice lacking lymphocytes are protected against hypertension, and adoptive transfer of T cells, but not B cells in the animals restores their blood pressure response to stimuli such as angiotensin II or high salt. Recent studies have shown that mice lacking macrophages have blunted hypertension in response to angiotensin II and that genetic deletion of macrophages markedly reduces experimental hypertension. Dendritic cells have also been implicated in this disease. Many hypertensive stimuli have triggering effects on the central nervous system and signals arising from the circumventricular organ seem to promote inflammation. Studies have suggested that central signals activate macrophages and T cells, which home to the kidney and vasculature and release cytokines, including IL-6 and IL-17, which in turn cause renal and vascular dysfunction and lead to blood pressure elevation. These recent discoveries provide a new understanding of hypertension and provide novel therapeutic opportunities for treatment of this serious disease.

  20. Imaging evaluation of fetal vascular anomalies

    International Nuclear Information System (INIS)

    Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal; Adams, Denise M.; Gupta, Anita; Lim, Foong-Yen

    2015-01-01

    Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification. (orig.)

  1. Imaging evaluation of fetal vascular anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Calvo-Garcia, Maria A.; Kline-Fath, Beth M.; Koch, Bernadette L.; Laor, Tal [MLC 5031 Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Adams, Denise M. [Cincinnati Children' s Hospital Medical Center, Department of Pediatrics and Hemangioma and Vascular Malformation Center, Cincinnati, OH (United States); Gupta, Anita [Cincinnati Children' s Hospital Medical Center, Department of Pathology, Cincinnati, OH (United States); Lim, Foong-Yen [Cincinnati Children' s Hospital Medical Center, Pediatric Surgery and Fetal Center of Cincinnati, Cincinnati, OH (United States)

    2015-08-15

    Vascular anomalies can be detected in utero and should be considered in the setting of solid, mixed or cystic lesions in the fetus. Evaluation of the gray-scale and color Doppler US and MRI characteristics can guide diagnosis. We present a case-based pictorial essay to illustrate the prenatal imaging characteristics in 11 pregnancies with vascular malformations (5 lymphatic malformations, 2 Klippel-Trenaunay syndrome, 1 venous-lymphatic malformation, 1 Parkes-Weber syndrome) and vascular tumors (1 congenital hemangioma, 1 kaposiform hemangioendothelioma). Concordance between prenatal and postnatal diagnoses is analyzed, with further discussion regarding potential pitfalls in identification. (orig.)

  2. Vascular ring complicates accidental button battery ingestion.

    Science.gov (United States)

    Mercer, Ronald W; Schwartz, Matthew C; Stephany, Joshua; Donnelly, Lane F; Franciosi, James P; Epelman, Monica

    2015-01-01

    Button battery ingestion can lead to dangerous complications, including vasculoesophageal fistula formation. The presence of a vascular ring may complicate battery ingestion if the battery lodges at the level of the ring and its important vascular structures. We report a 4-year-old boy with trisomy 21 who was diagnosed with a vascular ring at the time of button battery ingestion and died 9 days after presentation due to massive upper gastrointestinal bleeding from esophageal erosion and vasculoesophageal fistula formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Localized purpura revealing vascular prosthetic graft infection].

    Science.gov (United States)

    Boureau, A S; Lescalie, F; Cassagnau, E; Clairand, R; Connault, J

    2013-07-01

    Prosthetic graft infection after vascular reconstruction is a rare but serious complication. We report a case of infection occurring late after implantation of an iliofemoral prosthetic vascular graft. The Staphylococcus aureus infection was revealed by vascular purpura localized on the right leg 7 years after implantation of a vascular prosthesis. This case illustrates an uncommonly late clinical manifestation presenting as an acute infection 7 years after the primary operation. In this situation, the presentation differs from early infection, which generally occurs within the first four postoperative months. Diagnosis and treatment remain a difficult challenge because prosthetic graft infection is a potentially life-threatening complication. Morbidity and mortality rates are high. Here we detail specific aspects of the clinical and radiological presentation. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Vascular function in health, hypertension, and diabetes

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Gliemann, Lasse; Hellsten, Ylva

    2015-01-01

    muscle, which can affect muscle function. Central aspects in the vascular impairments are alterations in the formation of prostacyclin, the bioavailability of NO and an increased formation of vasoconstrictors and reactive oxygen species (ROS). Regular physical activity effectively improves vascular......, the increase in muscle blood flow required for oxygen supply during exercise is achieved through a substantial increase in vasodilators locally formed in the active muscle tissue that overcome the vasoconstrictor signals. Most of the vasodilator signals are mediated via endothelial cells, which lead...... to the formation of vasodilators such as nitric oxide (NO) and prostacyclin. In essential hypertension and type II diabetes, the endothelial function and regulation of vascular tone is impaired with consequent increases in peripheral vascular resistance and inadequate regulation of oxygen supply to the skeletal...

  5. Human genetics of diabetic vascular complications

    Indian Academy of Sciences (India)

    Abstract. Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the ..... cohort with nominal significance, and a recent meta-analysis ..... Whereas it is generally thought that lysine acetylation is.

  6. Incorporating simulation in vascular surgery education.

    Science.gov (United States)

    Bismuth, Jean; Donovan, Michael A; O'Malley, Marcia K; El Sayed, Hosam F; Naoum, Joseph J; Peden, Eric K; Davies, Mark G; Lumsden, Alan B

    2010-10-01

    The traditional apprenticeship model introduced by Halsted of "learning by doing" may just not be valid in the modern practice of vascular surgery. The model is often criticized for being somewhat unstructured because a resident's experience is based on what comes through the "door." In an attempt to promote uniformity of training, multiple national organizations are currently delineating standard curricula for each trainee to govern the knowledge and cases required in a vascular residency. However, the outcomes are anything but uniform. This means that we graduate vascular specialists with a surprisingly wide spectrum of abilities. Use of simulation may benefit trainees in attaining a level of technical expertise that will benefit themselves and their patients. Furthermore, there is likely a need to establish a simulation-based certification process for graduating trainees to further ascertain minimum technical abilities. Copyright © 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

  7. Audit of the Danish national vascular database

    DEFF Research Database (Denmark)

    Levi-Mazloum, Niels Donald; Jensen, L P; Schroeder, T V

    1996-01-01

    The accuracy of data contained in the Danish vascular database was compared with the case notes. A total of 100 case notes were reviewed for 11 pertinent variables in the database. A high error rate ranging from 2 to 34% was found. Also, approximately 10% of patients had never been entered into t...... into the vascular database. Further improvement of the Danish vascular database is necessary for its use as basis for reporting results.......The accuracy of data contained in the Danish vascular database was compared with the case notes. A total of 100 case notes were reviewed for 11 pertinent variables in the database. A high error rate ranging from 2 to 34% was found. Also, approximately 10% of patients had never been entered...

  8. Vascular adaptation to physical inactivity in humans.

    NARCIS (Netherlands)

    Bleeker, M.W.P.

    2006-01-01

    This thesis presents studies on vascular adaptation to physical inactivity and deconditioning. Although it is clear that physical inactivity is an important risk factor for cardiovascular disease, the underlying physiological mechanisms have not yet been elucidated. In contrast to physical

  9. Extracellular Matrix Molecules Facilitating Vascular Biointegration

    Directory of Open Access Journals (Sweden)

    Martin K.C. Ng

    2012-08-01

    Full Text Available All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials.

  10. Lipidomics in vascular health: current perspectives.

    Science.gov (United States)

    Kolovou, Genovefa; Kolovou, Vana; Mavrogeni, Sophie

    2015-01-01

    Identifying the mechanisms that convert a healthy vascular wall to an atherosclerotic wall is of major importance since the consequences may lead to a shortened lifespan. Classical risk factors (age, smoking, obesity, diabetes mellitus, hypertension, and dyslipidemia) may result in the progression of atherosclerotic lesions by processes including inflammation and lipid accumulation. Thus, the evaluation of blood lipids and the full lipid complement produced by cells, organisms, or tissues (lipidomics) is an issue of importance. In this review, we shall describe the recent progress in vascular health research using lipidomic advances. We will begin with an overview of vascular wall biology and lipids, followed by a short analysis of lipidomics. Finally, we shall focus on the clinical implications of lipidomics and studies that have examined lipidomic approaches and vascular health.

  11. Lower limb vascular dysfunction in cyclists

    Directory of Open Access Journals (Sweden)

    Thiago Ayala Melo Di Alencar

    2013-06-01

    Full Text Available Sports-related vascular insufficiency affecting the lower limbs is uncommon, and early signs and symptoms can be confused with musculoskeletal injuries. This is also the case among professional cyclists, who are always at the threshold between endurance and excess training. The aim of this review was to analyze the occurrence of vascular disorders in the lower limbs of cyclists and to discuss possible etiologies. Eighty-five texts, including papers and books, published from 1950 to 2012, were used. According to the literature reviewed, some cyclists receive a late diagnosis of vascular dysfunction due to a lack of familiarity of the medical team with this type of dysfunction. Data revealed that a reduced blood flow in the external iliac artery, especially on the left, is much more common than in the femoral and popliteal arteries, and that vascular impairment is responsible for the occurrence of early fatigue and reduced performance in cycling.

  12. Laser-assisted vascular anastomosis

    Science.gov (United States)

    Kao, Race L.; Tsao-Wu, George; Magovern, George J.

    1990-06-01

    The milliwatt CO2 laser and a thermal activated binding compound (20% serum albumin) were used for microvascular anastomoses. Under general anesthesia, the femoral arteries (0.7 to 1.0 mm diameter) of 6 rats were isolated. After the left femoral artery in each rat was clamped and transected, the vessel was held together with 3 equidistant 10-0 Xomed sutures. The cut edges were coated 3 to 4 times with the albumin solution and sealed with the CO2 laser (power density = 120 W/cm2). The binding compound solidified to a translucent tensile substance which supported the anastomosis until self healing and repair were achieved. The right femoral artery was used as sham operated control. Complete hemostasis and patency were observed in every case immediately and at 1, 3, and 6 months following surgery. The binding compound absorbed most of the laser energy thus minimizing thermal injury to the underlying tissue. Mongrel dogs weighing 28 to 33 kg were anesthetized and prepared for sterile surgical procedures. In 5 dogs, the femoral and jugular veins were exposed, transected, and anastomosed using a CO2 laser (Sharplan 1040) with the binding compound. In another 12 dogs, cephalic veins were isolated and used for aortocoronary artery bypass procedures. The Sharplan 1040 CO2 laser and 20% albumin solution were utilized to complete the coronary anastomoses in 6 dogs, and 6 dogs were used as controls by suturing the vessels. Again, hemostasis, patency, and minimal tissue damage were observed immediately and 6 weeks after the procedures. Improved surgical results, reduced operating time, minimized tissue damage, and enhanced anastomotic integrity are the advantages of laser assisted vascular anastomosis with a thermal activated binding compound.

  13. The vascular surgery workforce: a survey of consultant vascular surgeons in the UK, 2014.

    Science.gov (United States)

    Harkin, D W; Beard, J D; Shearman, C P; Wyatt, M G

    2015-04-01

    The purpose of this study was to describe the demographics, training, and practice characteristics of consultant vascular surgeons across the UK to provide an assessment of current, and inform future prediction of workforce needs. A questionnaire was developed using a modified Delphi process to generate questionnaire items. The questionnaire was emailed to all consultant vascular surgeons (n = 450) in the UK who were members of the Vascular Society of Great Britain & Ireland. 352 consultant vascular surgeons from 95 hospital trusts across the UK completed the survey (78% response rate). The mean age was 50.6 years old, the majority (62%) were mid-career, but 24% were above the age of 55. Currently, 92% are men and only 8% women. 93% work full-time, with 60% working >50 hours, and 21% working >60 hours per week. The average team was 5 to 6 (range 2-10) vascular surgeons, with 23% working in a large team of ≥8. 17% still work in small teams of ≤3. Over 90% of consultant vascular surgeons perform the major index vascular surgery procedures (aneurysm repair, carotid endarterectomy, infra-inguinal bypass, amputation). While 84% perform standard endovascular abdominal aortic aneurysm repair (EVAR), <50% perform more complex endovascular aortic therapy. The majority of vascular surgeons "like their job" (85%) and are "satisfied" (69%) with their job. 34% of consultant vascular surgeons indicated they were "extremely likely" to retire within the next 10 years. This study provides the first detailed analysis of the new specialty of vascular surgery as practiced in the UK. There is a need to plan for a significant expansion in the consultant vascular surgeon workforce in the UK over the next 10 years to maintain the status quo. Copyright © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  14. Biomimicry, vascular restenosis and coronary stents.

    Science.gov (United States)

    Schwartz, R S; van der Giessen, W J; Holmes, D R

    1998-01-01

    Biomimicry is in its earliest stages and is being considered in the realm of tissue engineering. If arterial implants are to limit neointimal thickening, purely passive structures cannot succeed. Bioactivity must be present, either by pharmacologic intervention or by fabricating a 'living stent' that contains active cellular material. As tissue engineering evolves, useful solutions will emerge from applying this knowledge directly to vascular biologic problems resulting from angioplasty, stenting, and vascular prosthesis research.

  15. The current role of vascular stents.

    Science.gov (United States)

    Busquet, J

    1993-09-01

    The limitations of percutaneous balloon angioplasty have favoured the development and the use of vascular endoprostheses or stents. These thin-walled metal devices maintain after expansion, an optimal and constant diameter for the vascular lumen. Restenosis, dissection, abrupt closure, residual stenosis or re-opened total occlusion represent appropriate indications for stenting. A large experience with non-coronary application of stents is currently available in iliac, femoro-popliteal and renal arteries, aorta, large veins.

  16. Vascular colitis: a report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Il; Han, Chang Yul; Han, Man Chung; Choo, Dong Woon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1973-04-15

    The authors report two cases of vascular colitis in Korean with a review of literature. Case I, 20 years old male had severe abdominal pain and bloody diarrhea. Case II was 57 years old male and complained severe abdominal pain. Barium enema colon study on each cases disclosed typical thumbprinting appearance of involved segment. Predisposing factor in case I appeared to be anaphylactoid purpura, and in case II distal obstruction due to adenocarcinoma. The mechanism of vascular was briefly discussed.

  17. Robotic vascular resections during Whipple procedure.

    Science.gov (United States)

    Allan, Bassan J; Novak, Stephanie M; Hogg, Melissa E; Zeh, Herbert J

    2018-01-01

    Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vascular resections. This report outlines our technique.

  18. Effects of ouabain on vascular reactivity

    Directory of Open Access Journals (Sweden)

    Vassallo D.V.

    1997-04-01

    Full Text Available Ouabain is an endogenous substance occurring in the plasma in the nanomolar range, that has been proposed to increase vascular resistance and induce hypertension. This substance acts on the a-subunit of Na+,K+-ATPase inhibiting the Na+-pump activity. In the vascular smooth muscle this effect leads to intracellular Na+ accumulation that reduces the activity of the Na+/Ca2+ exchanger and to an increased vascular tone. It was also suggested that circulating ouabain, even in the nanomolar range, sensitizes the vascular smooth muscle to vasopressor substances. We tested the latter hypothesis by studying the effects of ouabain in the micromolar and nanomolar range on phenylephrine (PE-evoked pressor responses. The experiments were performed in normotensive and hypertensive rats in vivo, under anesthesia, and in perfused rat tail vascular beds. The results showed that ouabain pretreatment increased the vasopressor responses to PE in vitro and in vivo. This sensitization after ouabain treatment was also observed in hypertensive animals which presented an enhanced vasopressor response to PE in comparison to normotensive animals. It is suggested that ouabain at nanomolar concentrations can sensitize vascular smooth muscle to vasopressor stimuli possibly contributing to increased tone in hypertension

  19. 3D bioprinting for vascularized tissue fabrication

    Science.gov (United States)

    Richards, Dylan; Jia, Jia; Yost, Michael; Markwald, Roger; Mei, Ying

    2016-01-01

    3D bioprinting holds remarkable promise for rapid fabrication of 3D tissue engineering constructs. Given its scalability, reproducibility, and precise multi-dimensional control that traditional fabrication methods do not provide, 3D bioprinting provides a powerful means to address one of the major challenges in tissue engineering: vascularization. Moderate success of current tissue engineering strategies have been attributed to the current inability to fabricate thick tissue engineering constructs that contain endogenous, engineered vasculature or nutrient channels that can integrate with the host tissue. Successful fabrication of a vascularized tissue construct requires synergy between high throughput, high-resolution bioprinting of larger perfusable channels and instructive bioink that promotes angiogenic sprouting and neovascularization. This review aims to cover the recent progress in the field of 3D bioprinting of vascularized tissues. It will cover the methods of bioprinting vascularized constructs, bioink for vascularization, and perspectives on recent innovations in 3D printing and biomaterials for the next generation of 3D bioprinting for vascularized tissue fabrication. PMID:27230253

  20. Vascular retraction driven by matrix softening

    Science.gov (United States)

    Valentine, Megan

    We recently discovered we can directly apply physical forces and monitor the downstream responses in a living organism in real time through manipulation of the blood vessels of a marine organism called, Botryllus schlosseri. The extracellular matrix (ECM) plays a key role in regulating vascular growth and homeostasis in Botryllus,a basal chordate which has a large, transparent extracorporeal vascular network that can encompass areas >100 cm2. We have determined that lysyl oxidase 1 (LOX1), which is responsible for cross-linking collagen, is expressed in all vascular cells and is critically important for vascular maintenance. Inhibition of LOX1 activity in vivo by the addition of a specific inhibitor, ß-aminopropionitrile (BAPN), caused a rapid, global regression of the entire vascular bed, with some vessels regressing >10 mm within 16 hrs. In this talk, I will discuss the molecular and cellular origins of this systemic remodeling event, which hinges upon the ability of the vascular cells to sense and respond to mechanical signals, while introducing this exciting new model system for studies of biological physics and mechanobiology. Collaborators: Anthony DeTomaso, Delany Rodriguez, Aimal Khankhel (UCSB).

  1. [Vascular aging, arterial hypertension and physical activity].

    Science.gov (United States)

    Schmidt-Trucksäss, A; Weisser, B

    2011-11-01

    The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Vascular Adventitia Calcification and Its Underlying Mechanism.

    Directory of Open Access Journals (Sweden)

    Na Li

    Full Text Available Previous research on vascular calcification has mainly focused on the vascular intima and media. However, we show here that vascular calcification may also occur in the adventitia. The purpose of this work is to help elucidate the pathogenic mechanisms underlying vascular calcification. The calcified lesions were examined by Von Kossa staining in ApoE-/- mice which were fed high fat diets (HFD for 48 weeks and human subjects aged 60 years and older that had died of coronary heart disease, heart failure or acute renal failure. Explant cultured fibroblasts and smooth muscle cells (SMCswere obtained from rat adventitia and media, respectively. After calcification induction, cells were collected for Alizarin Red S staining. Calcified lesions were observed in the aorta adventitia and coronary artery adventitia of ApoE-/-mice, as well as in the aorta adventitia of human subjects examined. Explant culture of fibroblasts, the primary cell type comprising the adventitia, was successfully induced for calcification after incubation with TGF-β1 (20 ng/ml + mineralization media for 4 days, and the phenotype conversion vascular adventitia fibroblasts into myofibroblasts was identified. Culture of SMCs, which comprise only a small percentage of all cells in the adventitia, in calcifying medium for 14 days resulted in significant calcification.Vascular calcification can occur in the adventitia. Adventitia calcification may arise from the fibroblasts which were transformed into myofibroblasts or smooth muscle cells.

  3. Patterns of peripheral vascular diseases at Muhimbili National hospital

    African Journals Online (AJOL)

    diseases) and HIV- vasculitis. A total of 97 patients (63%) were surgically treated. Conclusion: Shortage of vascular surgeons and facilities in our. Country needs to be sorted out to save life to these patients with vascular disorders. Key Words: Peripheral Vascular Diseases, and Shortage of Vascular Services in Tanzania.

  4. Lung irradiation induces pulmonary vascular remodelling resembling pulmonary arterial hypertension

    NARCIS (Netherlands)

    Ghobadi, G.; Bartelds, B.; van der Veen, S. J.; Dickinson, M. G.; Brandenburg, S.; Berger, R. M. F.; Langendijk, J. A.; Coppes, R. P.; van Luijk, P.

    Background Pulmonary arterial hypertension (PAH) is a commonly fatal pulmonary vascular disease that is often diagnosed late and is characterised by a progressive rise in pulmonary vascular resistance resulting from typical vascular remodelling. Recent data suggest that vascular damage plays an

  5. Vascular associated gene variants in patients with preeclampsia

    DEFF Research Database (Denmark)

    Lykke, Jacob A; Bare, Lance A; Olsen, Jørn

    2012-01-01

    Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms.......Preeclampsia has been linked to subsequent vascular disease with many shared predisposing factors. We investigated the association between severe preeclampsia, and its subtypes, and specific vascular-related polymorphisms....

  6. CDKL5 Gene-Related Epileptic Encephalopathy in Estonia: Four Cases, One Novel Mutation Causing Severe Phenotype in a Boy, and Overview of the Literature.

    Science.gov (United States)

    Lilles, Stella; Talvik, Inga; Noormets, Klari; Vaher, Ulvi; Õunap, Katrin; Reimand, Tiia; Sander, Valentin; Ilves, Pilvi; Talvik, Tiina

    2016-12-01

    Cyclin-dependent kinase-like 5 ( CDKL5 ) gene mutations have mainly been found in females with early infantile epileptic encephalopathy (EIEE), severe intellectual disability, and Rett-like features. To date, only 22 boys have been reported, presenting with far more severe phenotypic features. We report the first cases of CDKL5 gene-related EIEE in Estonia diagnosed using panels of epilepsy-associated genes and describe the phenotype-genotype correlations in three male and one female patient. One of the mutations, identified in a male patient, was a novel de novo hemizygous frameshift mutation (NM_003159.2:c.2225_2228del (p.Glu742Afs*41)) in exon 15 of CDKL5. All boys have a more severe phenotype than the female patient. In boys with early onset of seizures and poor development with absent or poor eye contact, CDKL5 gene-related EIEE can be suspected and epilepsy-associated genes should be analyzed for early etiological diagnosis. Early genetic diagnosis would be the cornerstone in personalized treatment in the future. Georg Thieme Verlag KG Stuttgart · New York.

  7. Sirtuins, Cell Senescence, and Vascular Aging.

    Science.gov (United States)

    Kida, Yujiro; Goligorsky, Michael S

    2016-05-01

    The sirtuins (SIRTs) constitute a class of proteins with nicotinamide adenine dinucleotide-dependent deacetylase or adenosine diphosphate-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, and SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition; and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, and contribute to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 show protective functions against vascular aging, and definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and nicotinamide adenine dinucleotide stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  8. Progenitor cells in pulmonary vascular remodeling

    Science.gov (United States)

    Yeager, Michael E.; Frid, Maria G.; Stenmark, Kurt R.

    2011-01-01

    Pulmonary hypertension is characterized by cellular and structural changes in the walls of pulmonary arteries. Intimal thickening and fibrosis, medial hypertrophy and fibroproliferative changes in the adventitia are commonly observed, as is the extension of smooth muscle into the previously non-muscularized vessels. A majority of these changes are associated with the enhanced presence of α-SM-actin+ cells and inflammatory cells. Atypical abundances of functionally distinct endothelial cells, particularly in the intima (plexiform lesions), and also in the perivascular regions, are also described. At present, neither the origin(s) of these cells nor the molecular mechanisms responsible for their accumulation, in any of the three compartments of the vessel wall, have been fully elucidated. The possibility that they arise from either resident vascular progenitors or bone marrow–derived progenitor cells is now well established. Resident vascular progenitor cells have been demonstrated to exist within the vessel wall, and in response to certain stimuli, to expand and express myofibroblastic, endothelial or even hematopoietic markers. Bone marrow–derived or circulating progenitor cells have also been shown to be recruited to sites of vascular injury and to assume both endothelial and SM-like phenotypes. Here, we review the data supporting the contributory role of vascular progenitors (including endothelial progenitor cells, smooth muscle progenitor cells, pericytes, and fibrocytes) in vascular remodeling. A more complete understanding of the processes by which progenitor cells modulate pulmonary vascular remodeling will undoubtedly herald a renaissance of therapies extending beyond the control of vascular tonicity and reduction of pulmonary artery pressure. PMID:22034593

  9. Congenital vascular malformations in scintigraphic evaluation

    International Nuclear Information System (INIS)

    Pilecki, Stanisław; Gierach, Marcin; Gierach, Joanna; Świętaszczyk, Cyprian; Junik, Roman; Lasek, Władysław

    2014-01-01

    Congenital vascular malformations are tumour-like, non-neoplastic lesions caused by disorders of vascular tissue morphogenesis. They are characterised by a normal cell replacement cycle throughout all growth phases and do not undergo spontaneous involution. Here we present a scintigraphic image of familial congenital vascular malformations in two sisters. A 17-years-old young woman with a history of multiple hospitalisations for foci of vascular anomalies appearing progressively in the upper and lower right limbs, chest wall and spleen. A Parkes Weber syndrome was diagnosed based on the clinical picture. Due to the occurrence of new foci of malformations, a whole-body scintigraphic examination was performed. A 12-years-old girl reported a lump in the right lower limb present for approximately 2 years, which was clinically identified as a vascular lesion in the area of calcaneus and talus. Phleboscintigraphy visualized normal radiomarker outflow from the feet via the deep venous system, also observed in the superficial venous system once the tourniquets were released. In static and whole-body examinations vascular malformations were visualised in the area of the medial cuneiform, navicular and talus bones of the left foot, as well as in the projection of right calcaneus and above the right talocrural joint. People with undiagnosed disorders related to the presence of vascular malformations should undergo periodic follow-up to identify lesions that may be the cause of potentially serious complications and to assess the results of treatment. Presented scintigraphic methods may be used for both diagnosing and monitoring of disease progression

  10. Gene transfer therapy in vascular diseases.

    Science.gov (United States)

    McKay, M J; Gaballa, M A

    2001-01-01

    Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of

  11. Adiposity, adipocytokines & microvesicles in the etiology of vascular disease

    OpenAIRE

    Kanhai, D.A.N.I.S.

    2013-01-01

    Vascular disease, in this thesis the terms vascular and cardiovascular are used interchangeably, is the number 1 cause of death worldwide. In 2008, 30% of all mortality had a vascular origin. Vascular mortality rates after a first manifestation of vascular disease are decreasing in Western society, which is attributable to better disease awareness, better preventive strategies and better healthcare systems. As mortality rates are decreasing, the number of patients surviving their first vascul...

  12. Open and endovascular aneurysm repair in the Society for Vascular Surgery Vascular Quality Initiative.

    Science.gov (United States)

    Spangler, Emily L; Beck, Adam W

    2017-12-01

    The Society for Vascular Surgery Vascular Quality Initiative is a patient safety organization and a collection of procedure-based registries that can be utilized for quality improvement initiatives and clinical outcomes research. The Vascular Quality Initiative consists of voluntary participation by centers to collect data prospectively on all consecutive cases within specific registries which physicians and centers elect to participate. The data capture extends from preoperative demographics and risk factors (including indications for operation), through the perioperative period, to outcomes data at up to 1-year of follow-up. Additionally, longer-term follow-up can be achieved by matching with Medicare claims data, providing long-term longitudinal follow-up for a majority of patients within the Vascular Quality Initiative registries. We present the unique characteristics of the Vascular Quality Initiative registries and highlight important insights gained specific to open and endovascular abdominal aortic aneurysm repair. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Preparation and features of polycaprolactone vascular grafts with the incorporated vascular endothelial growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Sevostyanova, V. V., E-mail: sevostyanova.victoria@gmail.com; Khodyrevskaya, Y. I.; Glushkova, T. V.; Antonova, L. V.; Kudryavtseva, Y. A.; Barbarash, O. L.; Barbarash, L. S. [Research Institute for Complex Issues of Cardiovascular Diseases, Kemerovo (Russian Federation)

    2015-10-27

    The development of tissue-engineered small-diameter vascular grafts is an urgent issue in cardiovascular surgery. In this study, we assessed how the incorporation of the vascular endothelial growth factor (VEGF) affects morphological and mechanical properties of polycaprolactone (PCL) vascular grafts along with its release kinetics. Vascular grafts were prepared using two-phase electrospinning. In pursuing our aims, we performed scanning electron microscopy, mechanical testing, and enzyme-linked immunosorbent assay. Our results demonstrated the preservation of a highly porous structure and improvement of PCL/VEGF scaffold mechanical properties as compared to PCL grafts. A prolonged VEGF release testifies the use of this construct as a scaffold for tissue-engineered vascular grafts.

  14. Effects of PPARγ ligands on vascular tone.

    Science.gov (United States)

    Salomone, Salvatore; Drago, Filippo

    2012-06-01

    Peroxisome Proliferator-Activated Receptor γ (PPARγ), originally described as a transcription factor for genes of carbohydrate and lipid metabolism, has been more recently studied in the context of cardiovascular pathophysiology. Here, we review the available data on PPARγ ligands as modulator of vascular tone. PPARγ ligands include: thiazolidinediones (used in the treatment of type 2 diabetes mellitus), glitazars (bind and activate both PPARγ and PPARα), and other experimental drugs (still in development) that exploit the chemistry of thiazolidinediones as a scaffold for PPARγ-independent pharmacological properties. In this review, we examine both short (mostly from in vitro data)- and long (mostly from in vivo data)-term effects of PPARγ ligands that extend from PPARγ-independent vascular effects to PPARγ-dependent gene expression. Because endothelium is a master regulator of vascular tone, we have attempted to differentiate between endothelium-dependent and endothelium-independent effects of PPARγ ligands. Based on available data, we conclude that PPARγ ligands appear to influence vascular tone in different experimental paradigms, most often in terms of vasodilatation (potentially increasing blood flow to some tissues). These effects on vascular tone, although potentially beneficial, must be weighed against specific cardiovascular warnings that may apply to some drugs, such as rosiglitazone.

  15. Insulin resistance: vascular function and exercise

    Directory of Open Access Journals (Sweden)

    Moon-Hyon Hwang

    2016-09-01

    Full Text Available Insulin resistance associated with metabolic syndrome and Type 2 diabetes mellitus is an epidemic metabolic disorder, which increases the risk of cardiovascular complications. Impaired vascular endothelial function is an early marker for atherosclerosis, which causes cardiovascular complications. Both experimental and clinical studies indicate that endothelial dysfunction in vasculatures occurs with insulin resistance. The associated physiological mechanisms are not fully appreciated yet, however, it seems that augmented oxidative stress, a physiological imbalance between oxidants and antioxidants, in vascular cells is a possible mechanism involved in various vascular beds with insulin resistance and hyperglycemia. Regardless of the inclusion of resistance exercise, aerobic exercise seems to be beneficial for vascular endothelial function in both large conduit and small resistance vessels in both clinical and experimental studies with insulin resistance. In clinical cases, aerobic exercise over 8 weeks with higher intensity seems more beneficial than the cases with shorter duration and lower intensity. However, more studies are needed in the future to elucidate the physiological mechanisms by which vascular endothelial function is impaired in insulin resistance and improved with aerobic exercise.

  16. Vascular trauma: selected historical reflections from the

    Directory of Open Access Journals (Sweden)

    Rich Norman M

    2011-04-01

    Full Text Available 【Abstract】In the spirit of international exchanges of knowledge with colleagues from all over the world, who are interested in the care and treatment of vascular trauma, we offer selected historical reflections from the western world on vascular trauma. Whereas there are a number of key individuals and a variety of events that are important to us in our writing, we know essentially nothing about what is written by other cultures and, particularly, the Chinese. It is well recognized around the world that Chinese surgeons are among the first to be highly successful in re-plantation of severed extremities, repairing both injured arteries and veins. Also, we recognize that there are contributions in other parts of the world, which are not well known to us collectively. Contributions from the Arabic speaking part of the world come to mind because there is periodic brief reference. We offer our perspective hoping that there will be one or more Chinese surgeons who will offer us the benefit of sharing their perspective on important historical contributions to the managing of vascular trauma outside of the western world, and, particularly, the English speaking literature. Once again, we encourage our colleagues in the Arabic speaking world to provide us with their perspective of the development and management of vascular trauma. Key words: Vascular system injuries; History; Western world; International educational exchange

  17. Arteriographic evaluation, in the perispheric vascular trauma

    International Nuclear Information System (INIS)

    Patino, Jairo Hernando; Granados, Ana Maria; Lopera B, Jorge; Prada W, Angela Maria

    1993-01-01

    136 patients were angiographically studied under the suspicion of perispheric vascular lesion submitted to the radiology department of the San Vicente de Paul University Hospital (H.U.S.VP.) Medellin Colombia. The majority of the patients were young with wounds caused by gunshots (79.4%). the must frequent angiographic indication was the proximity of the wound to a vascular path (44.5%). 63% of the patients with angiography indicative of abnormality needed surgery from which 21% were because of the proximity of the wound to a vascular path and 76% because of the mayor findings when admitted to the hospital. the possible complications as a result of the angiographic procedure were revised only find inc two mayor reactions to the contrast media. there were no late complications. Angiography is highlighting sensitive (100%) specific (98.5%) and secure in the evaluation of patients with perispheric vascular trauma. Due to the high number of false negatives when the physical examination is performed, every patient with a wound near a vascular path must be evaluated angiographically

  18. Endothelial dysfunction in metabolic and vascular disorders.

    Science.gov (United States)

    Polovina, Marija M; Potpara, Tatjana S

    2014-03-01

    Vascular endothelium has important regulatory functions in the cardiovascular system and a pivotal role in the maintenance of vascular health and metabolic homeostasis. It has long been recognized that endothelial dysfunction participates in the pathogenesis of atherosclerosis from early, preclinical lesions to advanced, thrombotic complications. In addition, endothelial dysfunction has been recently implicated in the development of insulin resistance and type 2 diabetes mellitus (T2DM). Considering that states of insulin resistance (eg, metabolic syndrome, impaired fasting glucose, impaired glucose tolerance, and T2DM) represent the most prevalent metabolic disorders and risk factors for atherosclerosis, it is of considerable scientific and clinical interest that both metabolic and vascular disorders have endothelial dysfunction as a common background. Importantly, endothelial dysfunction has been associated with adverse outcomes in patients with established cardiovascular disease, and a growing body of evidence indicates that endothelial dysfunction also imparts adverse prognosis in states of insulin resistance. In this review, we discuss the association of insulin resistance and T2DM with endothelial dysfunction and vascular disease, with a focus on the underlying mechanisms and prognostic implications of the endothelial dysfunction in metabolic and vascular disorders. We also address current therapeutic strategies for the improvement of endothelial dysfunction.

  19. Nanomedicine approaches in vascular disease: a review.

    Science.gov (United States)

    Gupta, Anirban Sen

    2011-12-01

    Nanomedicine approaches have revolutionized the treatment of cancer and vascular diseases, where the limitations of rapid nonspecific clearance, poor biodistribution and harmful side effects associated with direct systemic drug administration can be overcome by packaging the agents within sterically stabilized, long-circulating nanovehicles that can be further surface-modified with ligands to actively target cellular/molecular components of the disease. With significant advancements in genetics, proteomics, cellular and molecular biology and biomaterials engineering, the nanomedicine strategies have become progressively refined regarding the modulation of surface and bulk chemistry of the nanovehicles, control of drug release kinetics, manipulation of nanoconstruct geometry and integration of multiple functionalities on single nanoplatforms. The current review aims to capture the various nanomedicine approaches directed specifically toward vascular diseases during the past two decades. Analysis of the promises and limitations of these approaches will help identify and optimize vascular nanomedicine systems to enhance their efficacy and clinical translation in the future. Nanomedicine-based approaches have had a major impact on the treatment and diagnosis of malignancies and vascular diseases. This review discusses various nanomedicine approaches directed specifically toward vascular diseases during the past two decades, highlighting their advantages, limitations and offering new perspectives on future applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. The vascular pattern in the flower of some Mesembryanthemaceae: Aptenia cordifolia and Dorotheanthus bellidiformis. The effect of an ontogenetical shifting on the vascular pattern and vascular conservatism

    NARCIS (Netherlands)

    Meulen-Bruijns, van der C.

    1976-01-01

    1. The vascular pattern in the flower at various stages of maturity of Aptenia cordifolia and Dorotheanthus bellidiformis is examined. 2. The vascular pattern of Dorotheanthus has been compared with that of Aptenia: typologically, Dorotheanthus is derived from Aptenia. 3. The vascular pattern of

  1. Vascular training and endovascular practice in Europe

    DEFF Research Database (Denmark)

    Liapis, C.D.; Avgerinos, E.D.; Sillesen, H.

    2009-01-01

    specialties was distributed to a VS educator within 14 European countries. European Vascular and Endovascular Monitor (EVEM) data also were processed to correlate endovascular practice with training models. RESULTS: Fourteen questionnaires were gathered. Vascular training in Europe appears in 3 models: 1....... Mono-specialty (independence): 7 countries, 2. Subspecialty: 5 countries, 3. An existing specialty within general surgery: 2 countries. Independent compared to non-independent certification shortens overall training length (5.9 vs 7.9 years, p=0.006), while increasing overall training devoted......% respectively. Countries with independent vascular certification, despite their lower average endovascular index (procedures per 100,000 population), reported a higher growth rate of aortic endovascular procedures (VS independent 132% vs VS non-independent 87%), within a four-year period (2003-2007). Peripheral...

  2. Intraoperative digital angiography: Peripheral vascular applications

    International Nuclear Information System (INIS)

    Bell, K.; Reifsteck, J.E.; Binet, E.F.; Fleisher, H.J.

    1986-01-01

    Intraoperative digital angiography is the procedure of choice for the peripheral vascular surgeon who wishes to evaluate his results before terminating anesthesia. Two operating suites at the John L. McClellan Memorial Veterans Hospital are equipped with permanent ceiling-mounted Philips C-arm fluoroscopes and share an ADAC 4100 digital angiographic system. In the last 18 months, 40 peripheral vascular intraoperative digital angiographic procedures have been performed, in all but two cases using direct arterial puncture. In 65% of cases, the intraoperative study showed no significant abnormality. In 12.5%, minor abnormalities not requiring reoperation were seen. In 22.5% of cases, the intraoperative digital angiogram revealed a significant abnormality requiring immediate operative revision. None of the patients who underwent reoperation experienced postoperative sequelae. Intraoperative digital angiography is useful in identifying complications of peripheral vascular operations

  3. Viral haemorrhagic fever and vascular alterations.

    Science.gov (United States)

    Aleksandrowicz, P; Wolf, K; Falzarano, D; Feldmann, H; Seebach, J; Schnittler, H

    2008-02-01

    Pathogenesis of viral haemorrhagic fever (VHF) is closely associated with alterations of the vascular system. Among the virus families causing VHF, filoviruses (Marburg and Ebola) are the most fatal, and will be focused on here. After entering the body, Ebola primarily targets monocytes/macrophages and dendritic cells. Infected dendritic cells are largely impaired in their activation potency, likely contributing to the immune suppression that occurs during filovirus infection. Monocytes/macrophages, however, immediately activate after viral contact and release reasonable amounts of cytokines that target the vascular system, particularly the endothelial cells. Some underlying molecular mechanisms such as alteration of the vascular endothelial cadherin/catenin complex, tyrosine phosphorylation, expression of cell adhesion molecules, tissue factor and the effect of soluble viral proteins released from infected cells to the blood stream will be discussed.

  4. Vacuum assisted closure in vascular surgery.

    Science.gov (United States)

    Beno, M; Martin, J; Sager, P

    2011-01-01

    Vacuum assisted closure (VAC-therapy) is a well established method in nearly all surgical disciplines. The aim is to present the efficiency of vacuum assisted closure in the treatment of acute and chronic wounds in patients admitted in the department of vascular surgery. Within the year 2008 there were 59 patients (44 men, 15 women) treated with VAC therapy in our Department of Vascular surgery (Landshut, Germany). VAC was used 22x (37.28 %) in therapy of ulcus cruris (venous, arterial, mixed genesis), 15x (25.42%) in patients with diabetic foot syndrome, 12x (20.33%) in secondary healing wounds and infected wounds, 5x (8.47%) in wounds after several injuries and soft skin tissue infections and 5x (8.47%) in wound infections connected with vascular graft infections after vascular revascularization. VAC therapy seems to be very effective in the management of patients with venous ulcers, especially after a proper surgical treatment (100%), patients with soft skin tissue infections (100%) and secondary healing wounds (100%) especially in combination with MESH-Grafting. In patients with diabetic foot syndrome (80%) and peripheral arterial occlusive disease (72.7%), an evaluation of peripheral blood perfusion and revascularization prior to VAC therapy is often necessary. Although VAC was used 5x in the therapy of infected vascular grafts, successful preservation of infected graft material was observed in only one case (infection of PTFE femoro-popliteal bypass graft). Vacuum assisted closure in vascular surgery proved to be simple and efficient method in therapy of acute and chronic wounds. The efficiency of VAC systems in therapy of infected graft material after revascularization needs further studies (Tab. 3, Ref. 10).

  5. The pathology and pathophysiology of vascular dementia.

    Science.gov (United States)

    Kalaria, Raj N

    2017-12-19

    Vascular dementia (VaD) is widely recognised as the second most common type of dementia. Consensus and accurate diagnosis of clinically suspected VaD relies on wide-ranging clinical, neuropsychological and neuroimaging measures in life but more importantly pathological confirmation. Factors defining subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes as well as time after the initial vascular event. Atherosclerotic and cardioembolic diseases combined appear the most common subtypes of vascular brain injury. In recent years, cerebral small vessel disease (SVD) has gained prominence worldwide as an important substrate of cognitive impairment. SVD is characterised by arteriolosclerosis, lacunar infarcts and cortical and subcortical microinfarcts and diffuse white matter changes, which involve myelin loss and axonal abnormalities. Global brain atrophy and focal degeneration of the cerebrum including medial temporal lobe atrophy are also features of VaD similar to Alzheimer's disease. Hereditary arteriopathies have provided insights into the mechanisms of dementia particularly how arteriolosclerosis, a major contributor of SVD promotes cognitive impairment. Recently developed and validated neuropathology guidelines indicated that the best predictors of vascular cognitive impairment were small or lacunar infarcts, microinfarcts, perivascular space dilation, myelin loss, arteriolosclerosis and leptomeningeal cerebral amyloid angiopathy. While these substrates do not suggest high specificity, VaD is likely defined by key neuronal and dendro-synaptic changes resulting in executive dysfunction and related cognitive deficits. Greater understanding of the molecular pathology is needed to clearly define microvascular disease and vascular substrates of dementia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Perioperative smoking cessation in vascular surgery

    DEFF Research Database (Denmark)

    Kehlet, M.; Heesemann, Sabine; Tonnesen, H.

    2015-01-01

    Background: The effect of intensive smoking cessation programs on postoperative complications has never before been assessed in soft tissue surgery when smoking cessation is initiated on the day of surgery. Methods: A single-blinded randomized clinical trial conducted at two vascular surgery...... departments in Denmark. The intervention group was offered the Gold Standard Program (GSP) for smoking cessation intervention. The control group was offered the departments' standard care. Inclusion criteria were patients with planned open peripheral vascular surgery and who were daily smokers. According...

  7. Genealogy of training in vascular neurosurgery.

    Science.gov (United States)

    Chowdhry, Shakeel A; Spetzler, Robert F

    2014-02-01

    Remarkable advances and changes in the landscape of neurovascular disease have occurred recently. Concurrently, a paradigm shift in training and resident education is underway. This crossroad of unique opportunities and pressures necessitates creative change in the training of future vascular neurosurgeons to allow incorporation of surgical advances, new technology, and supplementary treatment modalities in a setting of reduced work hours and increased public scrutiny. This article discusses the changing landscape in neurovascular disease treatment, followed by the recent changes in resident training, and concludes with our view of the future of training in vascular neurosurgery.

  8. Vascularized Composite Allografts: Procurement, Allocation, and Implementation.

    Science.gov (United States)

    Rahmel, Axel

    Vascularized composite allotransplantation is a continuously evolving area of modern transplant medicine. Recently, vascularized composite allografts (VCAs) have been formally classified as 'organs'. In this review, key aspects of VCA procurement are discussed, with a special focus on interaction with the procurement of classical solid organs. In addition, options for a matching and allocation system that ensures VCA donor organs are allocated to the best-suited recipients are looked at. Finally, the different steps needed to promote VCA transplantation in society in general and in the medical community in particular are highlighted.

  9. Early vascular plants in the Czech Republic

    OpenAIRE

    Uhlířová, Monika

    2017-01-01

    Vascular plants are characterized as a group of plants, which are already fully adapted to live on the land. Their evolution is a result of a set of adaptations that have required the necessary changes at anatomical and morphological level. Some evidences about the rise of vascular plants appear in the fossil record from the Middle Ordovician in the form of spores and later also from the Early Silurian in the form of megafossils. The aim of the thesis is to briefly describe and discuss the mo...

  10. Radiological study of cerebro-vascular accidents

    International Nuclear Information System (INIS)

    Misri, H.T.; Kabawe, Bassam

    1991-01-01

    The role of computerized tomography scanner in studying the cerebro-vascular accidents has been discussed. One hundred fifty patients with cerebro-vascular accidents were studied at Aleppo University Hospital between 1989-1990. Clinical history and physical examination were recorded, as well as, computerized tomography scanning in all cases without using the contrast media mostly. Relationship between the density of the lesion (inforctionor hemorrhage) and the time has been found. This relationship can help in forensic medicine. (author). 29 refs., 5 tabs., 2 figs

  11. Angiogenesis and vascular targeting: Relevance for hyperthermia

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2008-01-01

    The creation of a functional blood supply from the normal tissue vasculature via the process of angiogenesis is critical for the continued growth and development of solid tumours. This importance has led to the concept of targeting the tumour vasculature as a therapeutic strategy, and two major...... types of vascular targeting agents (VTAs) have developed; those that inhibit the angiogenic process-angiogenesis inhibiting agents (AIAs)-and those that specifically damage the already established neovasculature-vascular disrupting agents (VDAs). The tumour vasculature also plays a critical role...

  12. Age related changes in tumor vascularity

    International Nuclear Information System (INIS)

    Loerelius, L.E.; Stridbeck, H.

    1984-01-01

    VX 2 tumors in the rabbit hind leg were investigated at one, two and three weeks of age. Angiograms were compared with vascular casts. The tumors grew rapidly the first two weeks of age. Large variations in vascularity were noted between tumors of different ages. With increasing age arteriovenous shunts at the tumor periphery and areas of avascularity of necrosis in the tumor center increased in size. Possible reasons for tumor necrosis are increased tissue pressure, anoxia caused by arteriovenous shunts and elevation in venous pressure. The natural history of the VX 2 tumor must be considered in every experimental study of the effect of any treatment. (orig.)

  13. Improving Technology for Vascular Imaging

    Science.gov (United States)

    Rana, Raman

    Neuro-endovascular image guided interventions (Neuro-EIGIs) is a minimally invasive procedure that require micro catheters and endovascular devices be inserted into the vasculature via an incision near the femoral artery and guided under low dose fluoroscopy to the vasculature of the head and neck. However, the endovascular devices used for the purpose are of very small size (stents are of the order of 50mum to 100mum) and the success of these EIGIs depends a lot on the accurate placement of these devices. In order to accurately place these devices inside the patient, the interventionalist should be able to see them clearly. Hence, high resolution capabilities are of immense importance in neuro-EIGIs. The high-resolution detectors, MAF-CCD and MAF-CMOS, at the Toshiba Stroke and Vascular Research Center at the University at Buffalo are capable of presenting improved images for better patient care. Focal spot of an x-ray tube plays an important role in performance of these high resolution detectors. The finite size of the focal spot results into the blurriness around the edges of the image of the object resulting in reduced spatial resolution. Hence, knowledge of accurate size of the focal spot of the x-ray tube is very essential for the evaluation of the total system performance. Importance of magnification and image detector blur deconvolution was demonstrated to carry out the more accurate measurement of x-ray focal spot using a pinhole camera. A 30 micron pinhole was used to obtain the focal spot images using flat panel detector (FPD) and different source to image distances (SIDs) were used to achieve different magnifications (3.16, 2.66 and 2.16). These focal spot images were deconvolved with a 2-D modulation transfer function (MTF), obtained using noise response (NR) method, to remove the detector blur present in the images. Using these corrected images, the accurate size of all the three focal spots were obtained and it was also established that effect of

  14. Genome-wide gene expression array identifies novel genes related to disease severity and excessive daytime sleepiness in patients with obstructive sleep apnea.

    Directory of Open Access Journals (Sweden)

    Yung-Che Chen

    Full Text Available We aimed to identify novel molecular associations between chronic intermittent hypoxia with re-oxygenation and adverse consequences in obstructive sleep apnea (OSA. We analyzed gene expression profiles of peripheral blood mononuclear cells from 48 patients with sleep-disordered breathing stratified into four groups: primary snoring (PS, moderate to severe OSA (MSO, very severe OSA (VSO, and very severe OSA patients on long-term continuous positive airway pressure treatment (VSOC. Comparisons of the microarray gene expression data identified eight genes up-regulated with OSA and down-regulated with CPAP treatment, and five genes down-regulated with OSA and up-regulated with CPAP treatment. Protein expression levels of two genes related to endothelial tight junction (AMOT P130, and PLEKHH3, and three genes related to anti-or pro-apoptosis (BIRC3, ADAR1 P150, and LGALS3 were all increased in the VSO group, while AMOT P130 was further increased, and PLEKHH3, BIRC3, and ADAR1 P150 were all decreased in the VSOC group. Subgroup analyses revealed that AMOT P130 protein expression was increased in OSA patients with excessive daytime sleepiness, BIRC3 protein expression was decreased in OSA patients with hypertension, and LGALS3 protein expression was increased in OSA patients with chronic kidney disease. In vitro short-term intermittent hypoxia with re-oxygenation experiment showed immediate over-expression of ADAR1 P150. In conclusion, we identified a novel association between AMOT/PLEKHH3/BIRC3/ADAR1/LGALS3 over-expressions and high severity index in OSA patients. AMOT and GALIG may constitute an important determinant for the development of hypersomnia and kidney injury, respectively, while BIRC3 may play a protective role in the development of hypertension.

  15. Large scale expression changes of genes related to neuronal signaling and developmental processes found in lateral septum of postpartum outbred mice.

    Directory of Open Access Journals (Sweden)

    Brian E Eisinger

    Full Text Available Coordinated gene expression changes across the CNS are required to produce the mammalian maternal phenotype. Lateral septum (LS is a brain region critically involved with aspects of maternal care, and we recently examined gene expression of whole septum (LS and medial septum in selectively bred maternal mice. Here, we expand on the prior study by 1 conducting microarray analysis solely on LS in virgin and postpartum mice, 2 using outbred mice, and 3 evaluating the role of sensory input on gene expression changes. Large scale changes in genes related to neuronal signaling were identified, including four GABAA receptor subunits. Subunits α4 and δ were downregulated in maternal LS, likely reflecting a reduction in the extrasynaptic, neurosteroid-sensitive α4/δ containing receptor subtype. Conversely, subunits ε and θ were increased in maternal LS. Fifteen K+ channel related genes showed altered expression, as did dopamine receptors Drd1a and Drd2 (both downregulated, hypocretin receptor 1 (Hcrtr1, kappa opioid receptor 1 (Oprk1, and transient receptor potential channel 4 (Trpc4. Expression of a large number of genes linked to developmental processes or cell differentiation were also altered in postpartum LS, including chemokine (C-X-C motif ligand 12 (Cxcl12, fatty acid binding protein 7 (Fabp7, plasma membrane proteolipid (Pllp, and suppressor of cytokine signaling 2 (Socs2. Additional genes that are linked to anxiety, such as glutathione reductase (Gsr, exhibited altered expression. Pathway analysis also identified changes in genes related to cyclic nucleotide metabolism, chromatin structure, and the Ras gene family. The sensory presence of pups was found to contribute to the altered expression of a subset of genes across all categories. This study suggests that both large changes in neuronal signaling and the possible terminal differentiation of neuronal and/or glial cells play important roles in producing the maternal state.

  16. Engineering the mechanical and biological properties of nanofibrous vascular grafts for in situ vascular tissue engineering.

    Science.gov (United States)

    Henry, Jeffrey J D; Yu, Jian; Wang, Aijun; Lee, Randall; Fang, Jun; Li, Song

    2017-08-17

    Synthetic small diameter vascular grafts have a high failure rate, and endothelialization is critical for preventing thrombosis and graft occlusion. A promising approach is in situ tissue engineering, whereby an acellular scaffold is implanted and provides stimulatory cues to guide the in situ remodeling into a functional blood vessel. An ideal scaffold should have sufficient binding sites for biomolecule immobilization and a mechanical property similar to native tissue. Here we developed a novel method to blend low molecular weight (LMW) elastic polymer during electrospinning process to increase conjugation sites and to improve the mechanical property of vascular grafts. LMW elastic polymer improved the elasticity of the scaffolds, and significantly increased the amount of heparin conjugated to the micro/nanofibrous scaffolds, which in turn increased the loading capacity of vascular endothelial growth factor (VEGF) and prolonged the release of VEGF. Vascular grafts were implanted into the carotid artery of rats to evaluate the in vivo performance. VEGF treatment significantly enhanced endothelium formation and the overall patency of vascular grafts. Heparin coating also increased cell infiltration into the electrospun grafts, thus increasing the production of collagen and elastin within the graft wall. This work demonstrates that LMW elastic polymer blending is an approach to engineer the mechanical and biological property of micro/nanofibrous vascular grafts for in situ vascular tissue engineering.

  17. Vascular plugs - A key companion to Interventionists - 'Just Plug it'.

    Science.gov (United States)

    Ramakrishnan, Sivasubramanian

    2015-01-01

    Vascular plugs are ideally suited to close extra-cardiac, high flowing vascular communications. The family of vascular plugs has expanded. Vascular plugs in general have a lower profile and the newer variants can be delivered even through a diagnostic catheter. These features make them versatile and easy to use. The Amplatzer vascular plugs are also used for closing intracardiac defects including coronary arterio-venous fistula and paravalvular leakage in an off-label fashion. In this review, the features of currently available vascular plugs are reviewed along with tips and tricks of using them in the cardiac catheterization laboratory. Copyright © 2015. Published by Elsevier B.V.

  18. Oscillation of Angiogenesis and Vascular Dropout in Progressive Human Vascular Disease. [Vascular Pattern as Useful Read-Out of Complex Molecular Signaling

    Science.gov (United States)

    Parsons-Wingerter, Patricia

    2010-01-01

    When analyzed by VESsel GENeration Analysis (VESGEN) software, vascular patterns provide useful integrative read-outs of complex, interacting molecular signaling pathways. Using VESGEN, we recently discovered and published our innovative, surprising findings that angiogenesis oscillated with vascular dropout throughout progression of diabetic retinopathy, a blinding vascular disease. Our findings provide a potential paradigm shift in the current prevailing view on progression and treatment of this disease, and a new early-stage window of regenerative therapeutic opportunities. The findings also suggest that angiogenesis may oscillate with vascular disease in a homeostatic-like manner during early stages of other inflammatory progressive diseases such as cancer and coronary vascular disease.

  19. Vascular risk factors, cognitve decline, and dementia

    Directory of Open Access Journals (Sweden)

    E Duron

    2008-04-01

    Full Text Available E Duron, Olivier HanonBroca Hospital, Paris, FranceAbstract: Dementia is one of the most important neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer’s disease and vascular dementia, leading to a devastating loss of autonomy. In view of the increasing longevity of populations worldwide, prevention of dementia has turned into a major public health challenge. In the past decade, several vascular risk factors have been found to be associated with vascular dementia but also Alzheimer’s disease. Some longitudinal studies, have found significant associations between hypertension, diabetus mellitus, and metabolic syndrome, assessed at middle age, and dementia. Studies assessing the link between hypercholesterolemia, atrial fibrillation, smoking, and dementia have given more conflicting results. Furthermore, some studies have highlighted the possible protective effect of antihypertensive therapy on cognition and some trials are evaluating the effects of statins and treatments for insulin resistance. Vascular risk factors and their treatments are a promising avenue of research for prevention of dementia, and further long-term, placebo-controlled, randomized studies, need to be performed.Keywords: dementia, hypertension, diabetus mellitus, hypercholesterolemia, metabolic syndrome

  20. Vascular anatomy in angiography for magnetic resonance

    International Nuclear Information System (INIS)

    Charry Lopez, Marco Luciano; Rivera Gomez, Juan Enrique

    1998-01-01

    A review of basic anatomical concepts and main variants, as well as some anatomical anomalies of the central nervous system vascularity, these concepts are considered essential for the interpretation of magnetic resonance angiography with time-of-flight (TOF) and phase-contrast (PC) methods

  1. CT imaging of cervical spinal vascular malformation

    International Nuclear Information System (INIS)

    Ueda, Takashi; Iwamoto, Munehisa; Miyamoto, Etsuo; Kuriyama, Tsuyoshi; Hayama, Tsuneto

    1982-01-01

    The patient had a history of the onset of motor paralysis of the right upper and lower extremities. Eight years later, numbness of the right upper extremity and a severe neck pain developed, and transverse paralysis of the lower extremities appeared in about 10 hours. CT demonstrated the presence of spinal vascular abnormality. Angiography suggested arteriovenous malformation of glomus type. (Chiba, N.)

  2. NEURO-VASCULAR INJURIES ASSOCIATED WITH LIMB ...

    African Journals Online (AJOL)

    hi-tech

    2000-12-01

    Dec 1, 2000 ... Subjects: Forty three patients with bone fractures associated with vascular and peripheral nerve injury seen at the Emergency Room of Assir Central Hospital from 1990 to 1999. There were 39 males and four females. Thirty five of these patients (81.4%) were Saudi nationals and the rest were non-Saudi.

  3. B vitamins influence vascular cognitive impairment

    Science.gov (United States)

    As the number of elderly in the USA and globally continues to increase, age-related neurological disorders, such as Alzheimer's disease and vascular dementia, are a growing concern. The loss of memory, emotional changes, and impairments in general cognitive functioning frequently result in social is...

  4. Quality Estimation for Vascular Pattern Recognition

    DEFF Research Database (Denmark)

    Hartung, Daniel; Martin, Sophie; Busch, Christoph

    2011-01-01

    The quality of captured samples is a critical aspect in biometric systems. In this paper we present a quality estimation algorithm for vascular images, which uses global and local features based on a Grey Level Co-Occurrence Matrix (GLCM) and optionally available metadata. An evaluation of the al...

  5. Self-management of vascular risk factors

    NARCIS (Netherlands)

    Sol-de Rijk, B.G.M.

    2009-01-01

    Summary The aim of this thesis was to provide insight into the potential of a self-management approach in treatment of vascular risk factors and to develop a self-management intervention. Furthermore to examine if this intervention, based on self-efficacy promoting theory, is effective in reducing

  6. Human genetics of diabetic vascular complications

    Indian Academy of Sciences (India)

    Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play ...

  7. CT imaging of cervical spinal vascular malformation

    Energy Technology Data Exchange (ETDEWEB)

    Ueda, Takashi; Iwamoto, Munehisa; Miyamoto, Etsuo; Kuriyama, Tsuyoshi; Hayama, Tsuneto [Wakayama Red Cross Hospital, Wakayama (Japan)

    1982-05-01

    The patient had a history of the onset of motor paralysis of the right upper and lower extremities. Eight years later, numbness of the right upper extremity and a severe neck pain developed, and transverse paralysis of the lower extremities appeared in about 10 hours. CT demonstrated the presence of spinal vascular abnormality. Angiography suggested arteriovenous malformation of glomus type.

  8. LASER TREATMENT OF BENIGN CUTANEOUS VASCULAR LESIONS

    Directory of Open Access Journals (Sweden)

    Uroš Ahčan

    2004-07-01

    Full Text Available Background. Congenital and acquired vascular lesions of the skin and subcutis are a common health problem from aesthetic and also from psycho-social point of view. However, recent advances in laser technology have enabled an efficient and safe treatment. This study presents our experience with treatment of cutaneous vascular lesions using modern laser systems. Most common benign cutaneous vascular lesions are described.Patients and methods. In years 2002 and 2003, 109 patients, 4 to 80 (mean 39 years old, Fitzpatrick skin type 1–4, with 210 benign cutaneous vascular lesions were treated using the Dualis VP® laser system (Fotona, Slovenia which incorporates the KTP and Nd:YAG lasers. Vascular lesions in the upper layers of the skin with diameter up to 1 mm were treated with the KTP laser (wavelength 532 nm. For larger vessels in deeper layer we used the Nd:YAG laser (wavelength 1064 nm. Patients graded the pain during treatment on a scale of 1–10. Clinical outcomes were evaluated 1–3 months after the last treatment: according to the percentage of clearance of the lesion compared to the adjacent normal skin and for the presence of adverse effects. According to these criteria each lesion was assigned a score: poor (0–25%, fair (26–50%, good (51–75%, excellent (76–100%.Results. Immediate response after application of a laser beam with proper characteristics was whitish-grey discoloration of treated area. Treatment results after 1–3 months were excellent in 48.1%, good 40.9%, fair in 8.6% and poor in 2.4%. Patients without prior anaesthesia graded pain during treatment from 1 to 8 (mean 4.0 and patients with EMLA® anaesthesia from 1 to 6 (mean 2.6. Side effects were frequent but minimal and transient. Erythema disappeared in several days after treatment while crusting persisted for 14 days. 3 permanent hyperpigmentations, 2 permanent hypopigmentations, 2 hypertrophic scars and 1 beam sized atrophic scar were detected at last follow

  9. Vascular Contributions to Cognitive Impairment and Dementia

    Science.gov (United States)

    Gorelick, Philip B.; Scuteri, Angelo; Black, Sandra E.; DeCarli, Charles; Greenberg, Steven M.; Iadecola, Costantino; Launer, Lenore J.; Laurent, Stephane; Lopez, Oscar L.; Nyenhuis, David; Petersen, Ronald C.; Schneider, Julie A.; Tzourio, Christophe; Arnett, Donna K.; Bennett, David A.; Chui, Helena C.; Higashida, Randall T.; Lindquist, Ruth; Nilsson, Peter M.; Roman, Gustavo C.; Sellke, Frank W.; Seshadri, Sudha

    2013-01-01

    Background and Purpose This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment and dementia of later life are common. Definitions of vascular cognitive impairment (VCI), neuropathology, basic science and pathophysiological aspects, role of neuroimaging and vascular and other associated risk factors, and potential opportunities for prevention and treatment are reviewed. This statement serves as an overall guide for practitioners to gain a better understanding of VCI and dementia, prevention, and treatment. Methods Writing group members were nominated by the writing group co-chairs on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council Scientific Statement Oversight Committee, the Council on Epidemiology and Prevention, and the Manuscript Oversight Committee. The writing group used systematic literature reviews (primarily covering publications from 1990 to May 1, 2010), previously published guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and, when appropriate, formulate recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on the recommendations and approved the final version of this document. After peer review by the American Heart Association, as well as review by the Stroke Council leadership, Council on Epidemiology and Prevention Council, and Scientific Statements Oversight Committee, the statement was approved by the American Heart Association Science Advisory and Coordinating Committee. Results The construct of VCI has been introduced to capture the entire spectrum of cognitive disorders associated with all forms of cerebral vascular brain injury—not solely stroke—ranging from mild cognitive impairment through fully developed

  10. GRECOS Project (Genotyping Recurrence Risk of Stroke): The Use of Genetics to Predict the Vascular Recurrence After Stroke.

    Science.gov (United States)

    Fernández-Cadenas, Israel; Mendióroz, Maite; Giralt, Dolors; Nafria, Cristina; Garcia, Elena; Carrera, Caty; Gallego-Fabrega, Cristina; Domingues-Montanari, Sophie; Delgado, Pilar; Ribó, Marc; Castellanos, Mar; Martínez, Sergi; Freijo, Marimar; Jiménez-Conde, Jordi; Rubiera, Marta; Alvarez-Sabín, José; Molina, Carlos A; Font, Maria Angels; Grau Olivares, Marta; Palomeras, Ernest; Perez de la Ossa, Natalia; Martinez-Zabaleta, Maite; Masjuan, Jaime; Moniche, Francisco; Canovas, David; Piñana, Carlos; Purroy, Francisco; Cocho, Dolores; Navas, Inma; Tejero, Carlos; Aymerich, Nuria; Cullell, Natalia; Muiño, Elena; Serena, Joaquín; Rubio, Francisco; Davalos, Antoni; Roquer, Jaume; Arenillas, Juan Francisco; Martí-Fábregas, Joan; Keene, Keith; Chen, Wei-Min; Worrall, Bradford; Sale, Michele; Arboix, Adrià; Krupinski, Jerzy; Montaner, Joan

    2017-05-01

    Vascular recurrence occurs in 11% of patients during the first year after ischemic stroke (IS) or transient ischemic attack. Clinical scores do not predict the whole vascular recurrence risk; therefore, we aimed to find genetic variants associated with recurrence that might improve the clinical predictive models in IS. We analyzed 256 polymorphisms from 115 candidate genes in 3 patient cohorts comprising 4482 IS or transient ischemic attack patients. The discovery cohort was prospectively recruited and included 1494 patients, 6.2% of them developed a new IS during the first year of follow-up. Replication analysis was performed in 2988 patients using SNPlex or HumanOmni1-Quad technology. We generated a predictive model using Cox regression (GRECOS score [Genotyping Reurrence Risk of Stroke]) and generated risk groups using a classification tree method. The analyses revealed that rs1800801 in the MGP gene (hazard ratio, 1.33; P =9×10 - 03 ), a gene related to artery calcification, was associated with new IS during the first year of follow-up. This polymorphism was replicated in a Spanish cohort (n=1.305); however, it was not significantly associated in a North American cohort (n=1.683). The GRECOS score predicted new IS ( P =3.2×10 - 09 ) and could classify patients, from low risk of stroke recurrence (1.9%) to high risk (12.6%). Moreover, the addition of genetic risk factors to the GRECOS score improves the prediction compared with previous Stroke Prognosis Instrument-II score ( P =0.03). The use of genetics could be useful to estimate vascular recurrence risk after IS. Genetic variability in the MGP gene was associated with vascular recurrence in the Spanish population. © 2017 American Heart Association, Inc.

  11. Coexistence of pheochromocytoma with uncommon vascular lesions

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2012-01-01

    Full Text Available Background: Pheochromocytoma/paragangliomas have been described to be associated with rare vascular abnormalities like renal artery stenosis. Coexistence of physiologically significant renal artery lesions is a compounding factor that alters management and prognosis of pheochromocytoma patients. Apart from individual case reports, data on such association in Indian population is not available. The aim of this study is to find the nature and prevalence of associated vascular abnormalities. Materials and Methods: From 1990 to 2010, a total of 50 patients were diagnosed with pheochromocytoma/paragangliomas. Hospital charts of these patients were reviewed retrospectively to identify those with unusual vascular abnormalities. Available literature was also reviewed. Results: Of the 50 patients with pheochromocytoma, 7 (14% had coexisting vascular lesions including renal artery stenosis in 4, aortoarteritis in 1, aortic aneurysm in 1 and inferior vena cava thrombosis in 1. Pheochromocytoma was adrenal in 42 and extra adrenal in 8. Laparoscopic adrenalectomy was done in the patients. One patient with renal artery stenosis due to intimal fibrosis was subjected to percutaneous balloon angioplasty; the other three improved after adrenalectomy and lysis of fibrous adhesive bands. The patient with aortoarteritos was treated with oral steroids. Inferior vena cava thrombosis was reversed with anticoagulants. The patient with abdominal aortic aneurysm was advised for annual follow-up on account of its size of 4.5 cm and asymptomatic presentation. Conclusion: There are multiple mechanisms that can lead to renal artery stenosis and other vascular abnormalities in a case of pheochromocytoma. A high index of suspicion is necessary to enable both entities to be diagnosed preoperatively and allow proper planning of surgical therapy. Incomplete diagnosis may lead to persistent hypertension postoperatively in a case of associated renal artery stenosis.

  12. The making of indigenous vascular prosthesis

    Directory of Open Access Journals (Sweden)

    Madathipat Unnikrishnan

    2016-01-01

    Full Text Available Background & objectives: Vascular illnesses are on the rise in India, due to increase in lifestyle diseases and demographic transition, requiring intervention to save life, organ or limbs using vascular prosthesis. The aim of this study was to develop indigenous large diameter vascular graft for treatment of patients with vascular pathologies. Methods: The South India Textile Research Association, at Coimbatore, Tamil Nadu, India, developed seamless woven polyester (Polyethylene terephthalate graft at its research wing. Further characterization and testing followed by clinical trials were conducted at Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India. Fifteen in vivo experiments were carried out in 1992-1994 in pigs as animal model. Controlled (phase I clinical trial in ten patients was performed along with control graft. Thereafter, phase II trial involved 22 patients who underwent multi-centre clinical trial in four centres across India. Results: Laboratory testing showed that polyester graft was non-toxic, non-leeching and non-haemolytic with preserved long-term quality, further confirming in pigs by implanting in thoracic aorta, comparable to control Dacron grafts. Perigraft incorporation and smooth neointima formation which are prime features of excellent healing characteristics, were noted at explantation at planned intervals. Subsequently in the phase I and II clinical trials, all patients had excellent recovery without mortality or device-related adverse events. Patients receiving the test graft were followed up for 10 and 5 years, respectively. Serial clinical, duplex scans and CT angiograms performed periodically confirmed excellent graft performance. Interpretation & conclusions: Indigenously developed Chitra vascular graft was comparable to commercially available Dacron graft, ready for clinical use at affordable cost to patients as against costly imported grafts.

  13. A biodegradable vascularizing membrane: a feasibility study.

    Science.gov (United States)

    Kaushiva, Anchal; Turzhitsky, Vladimir M; Darmoc, Marissa; Backman, Vadim; Ameer, Guillermo A

    2007-09-01

    Regenerative medicine and in vivo biosensor applications require the formation of mature vascular networks for long-term success. This study investigated whether biodegradable porous membranes could induce the formation of a vascularized fibrous capsule and, if so, the effect of degradation kinetics on neovascularization. Poly(l-lactic acid) (PLLA) and poly(dl-lactic-co-glycolic) acid (PLGA) membranes were created by a solvent casting/salt leaching method. Specifically, PLLA, PLGA 75:25 and PLGA 50:50 polymers were used to vary degradation kinetics. The membranes were designed to have an average 60mum pore diameter, as this pore size has been shown to be optimal for inducing blood vessel formation around nondegradable polymer materials. Membrane samples were imaged by scanning electron microscopy at several time points during in vitro degradation to assess any changes in pore structure. The in vivo performance of the membranes was assessed in Sprague-Dawley rats by measuring vascularization within the fibrous capsule that forms adjacent to implants. The vascular density within 100microm of the membranes was compared with that seen in normal tissue, and to that surrounding the commercially available vascularizing membrane TheraCyte. The hemoglobin content of tissue containing the membranes was measured by four-dimensional elastic light scattering as a novel method to assess tissue perfusion. Results from this study show that slow-degrading membranes induce greater amounts of neovascularization and a thinner fibrous capsule relative to fast degrading membranes. These results may be due both to an initially increased number of macrophages surrounding the slower degrading membranes and to the maintenance of their initial pore structure.

  14. Advanced Maternal Age Worsens Postpartum Vascular Function

    Directory of Open Access Journals (Sweden)

    Jude S. Morton

    2017-06-01

    Full Text Available The age at which women experience their first pregnancy has increased throughout the decades. Pregnancy has an important influence on maternal short- and long-term cardiovascular outcomes. Pregnancy at an advanced maternal age increases maternal risk of gestational diabetes, preeclampsia, placenta previa and caesarian delivery; complications which predict worsened cardiovascular health in later years. Aging also independently increases the risk of cardiovascular disease; therefore, combined risk in women of advanced maternal age may lead to detrimental cardiovascular outcomes later in life. We hypothesized that pregnancy at an advanced maternal age would lead to postpartum vascular dysfunction. We used a reproductively aged rat model to investigate vascular function in never pregnant (virgin, previously pregnant (postpartum and previously mated but never delivered (nulliparous rats at approximately 13.5 months of age (3 months postpartum or equivalent. Nulliparous rats, in which pregnancy was spontaneously lost, demonstrated significantly reduced aortic relaxation responses (methylcholine [MCh] Emax: 54.2 ± 12.6% vs. virgin and postpartum rats (MCh Emax: 84.8 ± 3.5% and 84.7 ± 3.2% respectively; suggesting pregnancy loss causes a worsened vascular pathology. Oxidized LDL reduced relaxation to MCh in aorta from virgin and postpartum, but not nulliparous rats, with an increased contribution of the LOX-1 receptor in the postpartum group. Further, in mesenteric arteries from postpartum rats, endothelium-derived hyperpolarization (EDH-mediated vasodilation was reduced and a constrictive prostaglandin effect was apparent. In conclusion, aged postpartum rats exhibited vascular dysfunction, while rats which had pregnancy loss demonstrated a distinct vascular pathology. These data demonstrate mechanisms which may lead to worsened outcomes at an advanced maternal age; including early pregnancy loss and later life cardiovascular dysfunction.

  15. Endovascular Management of Vascular Injury during Transsphenoidal Surgery

    OpenAIRE

    Çinar, C.; Bozkaya, H.; Parildar, M.; Oran, I.

    2013-01-01

    Vascular injury is an unusual and serious complication of transsphenoidal surgery. We aimed to define the role of angiography and endovascular treatment in patients with vascular injuries occurring during transsphenoidal surgery.

  16. Vascular effects of a single high salt meal

    Directory of Open Access Journals (Sweden)

    Mohamed Abdel Kader Abdel Wahab

    2016-09-01

    Conclusion: High salt intake may acutely impair vascular function in different vascular beds independent of the increase of blood pressure. Plasma sodium increase may be one of the underlying mechanisms.

  17. Vascular surgery research in the Gulf Cooperation Council countries

    Directory of Open Access Journals (Sweden)

    Ali Jawas

    2014-04-01

    Conclusion: The quality and quantity of vascular surgery research in the GCC countries should be improved to answer important local questions related to vascular diseases. This needs better strategic planning and more collaboration between various institutions.

  18. Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

    Science.gov (United States)

    Khalil, Raouf A

    2013-12-15

    Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Cell sheet engineering using the stromal vascular fraction of adipose tissue as a vascularization strategy

    OpenAIRE

    Costa, M.; Cerqueira, Mariana Teixeira; Santos, T. C.; Marques, Belém Sampaio; Ludovico, Paula; Marques, A. P.; Pirraco, Rogério P.; Reis, R. L.

    2017-01-01

    Current vascularization strategies for Tissue Engineering constructs, in particular cell sheet-based, are limited by time-consuming and expensive endothelial cell isolation and/or by the complexity of using extrinsic growth factors. Herein, we propose an alternative strategy using angiogenic cell sheets (CS) obtained from the stromal vascular fraction (SVF) of adipose tissue that can be incorporated into more complex constructs. Cells from the SVF were cultured in normoxic and hypoxic conditi...

  20. Deficiency of superoxide dismutase promotes cerebral vascular hypertrophy and vascular dysfunction in hyperhomocysteinemia.

    Directory of Open Access Journals (Sweden)

    Sanjana Dayal

    Full Text Available There is an emerging consensus that hyperhomocysteinemia is an independent risk factor for cerebral vascular disease and that homocysteine-lowering therapy protects from ischemic stroke. However, the mechanisms by which hyperhomocysteinemia produces abnormalities of cerebral vascular structure and function remain largely undefined. Our objective in this study was to define the mechanistic role of superoxide in hyperhomocysteinemia-induced cerebral vascular dysfunction and hypertrophy. Unlike previous studies, our experimental design included a genetic approach to alter superoxide levels by using superoxide dismutase 1 (SOD1-deficient mice fed a high methionine/low folate diet to produce hyperhomocysteinemia. In wild-type mice, the hyperhomocysteinemic diet caused elevated superoxide levels and impaired responses to endothelium-dependent vasodilators in cerebral arterioles, and SOD1 deficiency compounded the severity of these effects. The cross-sectional area of the pial arteriolar wall was markedly increased in mice with SOD1 deficiency, and the hyperhomocysteinemic diet sensitized SOD1-deficient mice to this hypertrophic effect. Analysis of individual components of the vascular wall demonstrated a significant increase in the content of smooth muscle and elastin. We conclude that superoxide is a key driver of both cerebral vascular hypertrophy and vasomotor dysfunction in this model of dietary hyperhomocysteinemia. These findings provide insight into the mechanisms by which hyperhomocysteinemia promotes cerebral vascular disease and ischemic stroke.

  1. Using biplanar fluoroscopy to guide radiopaque vascular injections: a new method for vascular imaging.

    Directory of Open Access Journals (Sweden)

    Haley D O'Brien

    Full Text Available Studying vascular anatomy, especially in the context of relationships with hard tissues, is of great interest to biologists. Vascular studies have provided significant insight into physiology, function, phylogenetic relationships, and evolutionary patterns. Injection of resin or latex into the vascular system has been a standard technique for decades. There has been a recent surge in popularity of more modern methods, especially radiopaque latex vascular injection followed by CT scanning and digital "dissection." This technique best displays both blood vessels and bone, and allows injections to be performed on cadaveric specimens. Vascular injection is risky, however, because it is not a standardizable technique, as each specimen is variable with regard to injection pressure and timing. Moreover, it is not possible to view the perfusion of injection medium throughout the vascular system of interest. Both data and rare specimens can therefore be lost due to poor or excessive perfusion. Here, we use biplanar video fluoroscopy as a technique to guide craniovascular radiopaque latex injection. Cadaveric domestic pigs (Sus scrofa domestica and white-tailed deer (Odocoileus virginianus were injected with radiopaque latex under guidance of fluoroscopy. This method was found to enable adjustments, in real-time, to the rate, location, and pressure at which latex is injected in order to avoid data and specimen loss. In addition to visualizing the injection process, this technique can be used to determine flow patterns, and has facilitated the development of consistent markers for complete perfusion.

  2. Joint Global War on Terror (GWOT) Vascular Injury Study 2

    Science.gov (United States)

    2017-02-01

    acquired in Iraq and Afghanistan, Society for Trauma Nurse, 2-4 April 2014, poster presentation o Vascular discharge education and follow-up care...eventual quality of limb and psychological recovery or well-being. 15. SUBJECT TERMS extremity vascular injury, extremity, vascular injury, vascular... psychological recovery or well-being. Finally, this program aims to characterize and compare the physical and emotional burden in large cohorts of US

  3. Childhood Vascular Tumors Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Childhood vascular tumors form from cells that make blood vessels or lymph vessels. They can be benign (not cancer) or malignant (cancer). Get information about the symptoms, tests to diagnose, prognosis, and treatment of the most common type of vascular tumor, infantile hemangioma, and other vascular tumors in this expert-reviewed summary.

  4. The evolution of development of vascular cambia and secondary growth

    Science.gov (United States)

    Andrew Groover; Rachel Spicer

    2010-01-01

    Secondary growth from vascular cambia results in radial, woody growth of stems. The innovation of secondary vascular development during plant evolution allowed the production of novel plant forms ranging from massive forest trees to flexible, woody lianas. We present examples of the extensive phylogenetic variation in secondary vascular growth and discuss current...

  5. Transglycosylated Starch Modulates the Gut Microbiome and Expression of Genes Related to Lipid Synthesis in Liver and Adipose Tissue of Pigs

    Directory of Open Access Journals (Sweden)

    Monica A. Newman

    2018-02-01

    Full Text Available Dietary inclusion of resistant starches can promote host health through modulation of the gastrointestinal microbiota, short-chain fatty acid (SCFA profiles, and lipid metabolism. This study investigated the impact of a transglycosylated cornstarch (TGS on gastric, ileal, cecal, proximal-colonic, and mid-colonic bacterial community profiles and fermentation metabolites using a growing pig model. It additionally evaluated the effect of TGS on the expression of host genes related to glucose and SCFA absorption, incretins, and satiety in the gut as well as host genes related to lipid metabolism in hepatic and adipose tissue. Sixteen growing pigs (4 months of age were fed either a TGS or control (CON diet for 11 days. Bacterial profiles were determined via Illumina MiSeq sequencing of the V3–5 region of the 16S rRNA gene, whereas SCFA and gene expression were measured using gas chromatography and reverse transcription-quantitative PCR. Megasphaera, which was increased at all gut sites, began to benefit from TGS feeding in gastric digesta, likely through cross-feeding with other microbes, such as Lactobacillus. Shifts in the bacterial profiles from dietary TGS consumption in the cecum, proximal colon, and mid colon were similar. Relative abundances of Ruminococcus and unclassified Ruminococcaceae genus were lower, whereas that of unclassified Veillonellaceae genus was higher in TGS- compared to CON-fed pigs (p < 0.05. TGS consumption also increased (p < 0.05 concentrations of SCFA, especially propionate, and lactate in the distal hindgut compared to the CON diet which might have up-regulated GLP1 expression in the cecum (p < 0.05 and mid colon compared to the control diet (p < 0.10. TGS-fed pigs showed increased hepatic and decreased adipocyte expression of genes for lipid synthesis (FASN, SREBP1, and ACACA compared to CON-fed pigs, which may be related to postprandial portal nutrient flow and reduced systemic insulin signaling. Overall, our data

  6. Development of the Australasian vascular surgical audit.

    Science.gov (United States)

    Bourke, Bernie M; Beiles, Charles Barry; Thomson, Ian A; Grigg, Michael J; Fitridge, Rob

    2012-01-01

    The purpose of this study was to describe the development of the Australasian Vascular Audit that was created to unify audit activities under the umbrella of the Australian and New Zealand Society for Vascular Surgery as a Web-based application. Constitutional change in late 2008 deemed participation in this audit compulsory for Society members. The Web-based application was developed and tested during 2009. Data for all open vascular surgery and for all endovascular procedures are collected at two points in the admission episode: at the time of operation and at discharge, and entered into the application. Data are analyzed to produce risk-adjusted outcomes. An algorithm has been developed to deal with outliers according to natural justice and to comply with the requirements of regulatory bodies. The Audit is protected by legislated privilege and is officially endorsed and indemnified by the Royal Australasian College of Surgeons. Confidentiality of surgeons and patients alike is ensured by a legally protected coding system and computer encryption system. Validation is by a verification process of 5% of members per year who are randomly selected. The application is completely funded by the Society. Data entry commenced on January 1, 2010. Over 40,000 vascular procedures were entered in the first year. The Audit application allows instantaneous on-line access to individual data and to deidentified group data and specific reports. It also allows real-time instantaneous production of log books for vascular trainees. The Audit has already gained recognition in the Australasian public arena during its first year of operation as an important benchmark of correct professional surgical behavior. Compliance has been extremely high in public hospitals but less so in private hospitals such that only 60% of members received a certificate of complete participation at the end of its first year of operation. An Internet-based compulsory audit of complete surgical practice is

  7. Management of vascular trauma from dog bites.

    Science.gov (United States)

    Akingba, A George; Robinson, Eric A; Jester, Andrea L; Rapp, Brian M; Tsai, Anthony; Motaganahalli, Raghu L; Dalsing, Michael C; Murphy, Michael P

    2013-11-01

    Vascular trauma from large-dog bites present with a combination of crush and lacerating injuries to the vessel, as well as significant adjacent soft tissue injury and a high potential for wound complications. This retrospective case series evaluates our 15 years of experience in managing this uncommonly seen injury into suggested treatment recommendations. From our database, 371 adult patients presented with dog bites between July 1997 and June 2012. Twenty (5.4%) of those patients had vascular injuries requiring surgical intervention. Patient demographics, anatomic location of injury, clinical presentation, imaging modality, method of repair, and complication rates were reviewed to assess efficacy in preserving limb function. Pediatric patients were managed at the regional children's hospital and, therefore, not included in this study. Among the 20 surgically treated vascular injuries, there were 13 arterial-only injuries, two venous-only injuries, and five combination arterial and venous injuries. Seventeen patients (85%) had upper extremity injuries; three patients had lower extremity injuries (15%). The axillobrachial artery was the most commonly injured single vessel (n = 9/20; 45%), followed by the radial artery (n = 4/20; 20%). Surgical repair of vascular injuries consisted of resection and primary anastomosis (four), interposition bypass of artery with autogenous vein (13), and ligation (two), with (one) being a combination of bypass and ligation. All patients had debridement of devitalized tissue combined with pulse lavage irrigation and perioperative antibiotics. Associated injuries requiring repair included muscle and skin (n = 10/20; 50%), bone (n = 1/20; 5%), nerve (n = 1/20; 5%), and combinations of the three (n = 5/20; 25%). Postoperative antibiotic therapy was administered for 14.7 ± 8.2 days in all 20 patients. Four patients (20%) developed postoperative wound infections, although this did not compromise their vascular repair. Of the patients

  8. Multinephron dynamics on the renal vascular network

    DEFF Research Database (Denmark)

    Marsh, Donald J; Wexler, Anthony S; Brazhe, Alexey

    2012-01-01

    Tubuloglomerular feedback (TGF) and the myogenic mechanism combine in each nephron to regulate blood flow and glomerular filtration rate. Both mechanisms are non-linear, generate self-sustained oscillations, and interact as their signals converge on arteriolar smooth muscle, forming a regulatory...... clusters. In-phase synchronization predominated among nephrons separated by 1 or 3 vascular nodes, and anti-phase synchronization for 5 or 7 nodes of separation. Nephron dynamics were irregular and contained low frequency fluctuations. Results are consistent with simultaneous blood flow measurements...... of both mechanisms in the regulatory ensemble, to examine the effects of network structure on nephron synchronization. Symmetry, as a property of a network, facilitates synchronization. Nephrons received blood from a symmetric electrically conductive vascular tree. Symmetry was created by using identical...

  9. Cocoa, Blood Pressure, and Vascular Function

    Science.gov (United States)

    Ludovici, Valeria; Barthelmes, Jens; Nägele, Matthias P.; Enseleit, Frank; Ferri, Claudio; Flammer, Andreas J.; Ruschitzka, Frank; Sudano, Isabella

    2017-01-01

    Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function. PMID:28824916

  10. Vascular anatomy of the spinal cord

    International Nuclear Information System (INIS)

    Thron, A.K.

    1988-01-01

    The book summarizes the anatomic guidelines of external blood supply to the spinal cord. The basic principles of arterial supply and venous drainage are illustrated by explicit schemes for quick orientation. In the first part of the book, systematic radiologic-anatomic investigations of the superficial and deep vessels of all segments of the spinal cord are introduced. The microvascular morphology is portrayed by numerous microradiographic sections in all three dimensions without overshadowing. The three-dimensional representation of the vascular architecture illustrates elementary outlines and details of arterial territories, anastomotic cross-linking as well as the capillary system, particularly the hitherto unknown structure of the medullary venous system with its functionally important anastomoses and varying regional structures. These often now radiologic-anatomic findings are discussed as to their functional and pathophysiologic impact and constitute the basic on which to improve one's understanding of vascular syndromes of the spinal cord

  11. Features and selection of vascular access devices.

    Science.gov (United States)

    Sansivero, Gail Egan

    2010-05-01

    To review venous anatomy and physiology, discuss assessment parameters before vascular access device (VAD) placement, and review VAD options. Journal articles, personal experience. A number of VAD options are available in clinical practice. Access planning should include comprehensive assessment, with attention to patient participation in the planning and selection process. Careful consideration should be given to long-term access needs and preservation of access sites. Oncology nurses are uniquely suited to perform a key role in VAD planning and placement. With knowledge of infusion therapy, anatomy and physiology, device options, and community resources, nurses can be key leaders in preserving vascular access and improving the safety and comfort of infusion therapy. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Ample spectrum of vascular hepatic disease

    International Nuclear Information System (INIS)

    Camacho, Juan C; Marquez Adriana; Romero, Javier; Aguirre Diego

    2010-01-01

    Hepatic vascular diseases (HVD) are a broad spectrum of entities of low prevalence but with different clinical manifestations that may even lead to death. Its early detection and timely treatment may change the prognosis. Diagnostic imaging plays a key role and imaging findings may be typical. However, in most cases, radiologists must take into account a wide range of differential diagnosis. Computed tomography (CT) of the abdomen is one of the most useful tools for the diagnosis of HVD taking also into account the value of other imaging methods such as Doppler Ultrasound and Magnetic Resonance Imaging (MRI). HVD can be classified according to the compromised vascular structure and can be divided into venous, portal, arterial, sinusoidal and others disorders. The objective of this review is to describe the most common presentation HVD. The major imaging findings and differential diagnosis recognizing its correlation with the pathophysiological mechanisms.

  13. Cocoa, blood pressure, and vascular function.

    Science.gov (United States)

    Sudano, Isabella; Flammer, Andreas J; Roas, Susanne; Enseleit, Frank; Ruschitzka, Frank; Corti, Roberto; Noll, Georg

    2012-08-01

    The consumption of a high amount of fruits and vegetables was found to be associated with a lower risk of coronary heart disease and stroke. Epidemiologically, a similar relationship has been found with cocoa, a naturally polyphenol-rich food. Obviously, double blind randomized studies are difficult to perform with cocoa and chocolate, respectively. However, intervention studies strongly suggest that cocoa has several beneficial effects on cardiovascular health, including the lowering of blood pressure, the improvement of vascular function and glucose metabolism, and the reduction of platelet aggregation and adhesion. Several potential mechanisms through which cocoa might exert its positive effects have been proposed, among them activation of nitric oxide synthase, increased bioavailability of nitric oxide as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on blood pressure and vascular function.

  14. Vascularization of soft tissue engineering constructs

    DEFF Research Database (Denmark)

    Pimentel Carletto, Rodrigo

    nanotechnology-based paradigm for engineering vascularised liver tissue for transplantation”) and the Danish National Research Foundation and Villum Foundation’s Center for Intelligent Drug delivery and sensing Using microcontainers and Nanomechanics (Danish National Research Foundation (DNRF122).......Vascularization is recognized to be the biggest challenge for the fabrication of tissues and finally, organs in vitro. So far, several fabrication techniques have been proposed to create a perfusable vasculature within hydrogels, however, the vascularization and perfusion of hydrogels...... with mechanical properties in the range of soft tissues has not been fully achieved. My project focused on the fabrication and the active perfusion of hydrogel constructs with multi-dimensional vasculature and controlled mechanical properties targeting soft tissues. Specifically, the initial part of the research...

  15. Cocoa, Blood Pressure, and Vascular Function

    Directory of Open Access Journals (Sweden)

    Valeria Ludovici

    2017-08-01

    Full Text Available Cardiovascular disease (CVD represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP, improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking or established CVD (coronary heart disease or heart failure. Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

  16. Noninvasive studies of peripheral vascular disease

    International Nuclear Information System (INIS)

    Yao, J.S.T.

    1987-01-01

    Plethysmography probably is the oldest method for measuring blood flow. In this method, measurements are made of changes in volume of an organ or region of tissue. In the modern practice of vascular surgery, the use of plethysmography has been expanded to include detection of not only arterial occlusive disease but also carotid artery disease and venous problems. Several types of plethysmographs are now available for clinical use in the evaluation of arterial occlusions. These are volume, strain-gauge, and photoelectric plethysmographs. The water-filled volume recorder, popular in the early use of plethysmography, is now obsolete and has been replaced by the air-filled volume plethysmograph, notably, the pulse-volume recorder. For clinical application, the newer plethysmographs, such as the strain-gauge, photopletyhsmograph, and pulse-volume recorder, are now standard equipment in many vascular laboratories. They are discussed in this article

  17. Biophysical Regulation of Vascular Differentiation and Assembly

    CERN Document Server

    Gerecht, Sharon

    2011-01-01

    The ability to grow stem cells in the laboratory and to guide their maturation to functional cells allows us to study the underlying mechanisms that govern vasculature differentiation and assembly in health and disease. Accumulating evidence suggests that early stages of vascular growth are exquisitely tuned by biophysical cues from the microenvironment, yet the scientific understanding of such cellular environments is still in its infancy. Comprehending these processes sufficiently to manipulate them would pave the way to controlling blood vessel growth in therapeutic applications. This book assembles the works and views of experts from various disciplines to provide a unique perspective on how different aspects of its microenvironment regulate the differentiation and assembly of the vasculature. In particular, it describes recent efforts to exploit modern engineering techniques to study and manipulate various biophysical cues. Biophysical Regulation of Vascular Differentiation and Assembly provides an inter...

  18. Vascular endothelium receptors and transduction mechanisms

    CERN Document Server

    Gillis, C; Ryan, Una; Proceedings of the Advanced Studies Institute on "Vascular Endothelium: Receptors and Transduction Mechanisms"

    1989-01-01

    Beyond their obvious role of a barrier between blood and tissue, vascular endothelial cells are now firmly established as active and essential participants in a host of crucial physiological and pathophysiological functions. Probably the two most important factors responsible for promoting the current knowledge of endothelial functions are 1) observations in the late sixties-early seventies that many non-ventilatory properties of the lung could be attributed to the pulmonary endothelium and 2) the establishment, in the early and mid-seventies of procedures for routine culture of vascular endothelial cells. Many of these endothelial functions require the presence of receptors on the surface of the plasma membrane. There is now evidence for the existence among others of muscarinic, a-and /3-adrenergic, purine, insulin, histamine, bradykinin, lipoprotein, thrombin, paf, fibronectin, vitronectin, interleukin and albumin receptors. For some of these ligands, there is evidence only for the existence of endothelial ...

  19. Vascular anomalies of the cerebellopontine angle

    International Nuclear Information System (INIS)

    Papanagiotou, P.; Grunwald, I.Q.; Politi, M.; Struffert, T.; Ahlhelm, F.; Reith, W.

    2006-01-01

    Vascular anomalies of the cerebellopontine angle are rare compared to tumors in this area. Irritation of the trigeminal, facial, or vestibulocochlear nerve may cause trigeminal neuralgia, hemifacial spasm and vertigo, or tinnitus accordingly. Vessel loops in the cerebellopontine cisterns may cause compression at the root entry or exit zone of the cranial nerves V, VII, and VIII, a phenomenon which is called ''vascular loop syndrome.'' Megadolichobasilar artery and aneurysms of the vertebrobasilar system can also lead to dislocation and compression of the cranial nerves and brain stem. Three-dimensional CISS MR imaging and MR angiography are useful in the detection of neurovascular compression. Microvascular decompression is an effective surgical procedure in the management of compression syndromes of the cranial nerves V, VII, and VIII. (orig.) [de

  20. Molecular parallels between neural and vascular development.

    Science.gov (United States)

    Eichmann, Anne; Thomas, Jean-Léon

    2013-01-01

    The human central nervous system (CNS) features a network of ~400 miles of blood vessels that receives >20% of the body's cardiac output and uses most of its blood glucose. Many human diseases, including stroke, retinopathy, and cancer, are associated with the biology of CNS blood vessels. These vessels originate from extrinsic cell populations, including endothelial cells and pericytes that colonize the CNS and interact with glia and neurons to establish the blood-brain barrier and control cerebrovascular exchanges. Neurovascular interactions also play important roles in adult neurogenic niches, which harbor a unique population of neural stem cells that are intimately associated with blood vessels. We here review the cellular and molecular mechanisms required to establish the CNS vascular network, with a special focus on neurovascular interactions and the functions of vascular endothelial growth factors.

  1. Treatment of hemobilia by transcatheter vascular occlusion

    International Nuclear Information System (INIS)

    Vaughan, R.; Roesch, J.; Keller, F.S.; Antonovic, R.; Veterans Administration Medical Center, Portland, OR

    1984-01-01

    Four cases of hemobilia treated by transcatheter arterial occlusion are presented and reviewed with 30 similar cases reported in the literature. Transcatheter vascular occlusion successfully controlled hemorrhage in all 34 patients. No obvious liver parenchymal damage appeared in 26 patients; transient elevation of liver enzymes occurred in 6 patients (18%) including one in our series; two of the patients reviewed died of acute hepatic insufficiency following nonselective hepatic artery embolization. Hemobilia should be considered when gastrointestinal hemorrhage occurs after abdominal trauma, liver biopsy or other manipulative liver procedures. Hepatic angiography establishes the diagnosis and selective vascular occlusion is the treatment of choice for control of intractable or recurrent hemorrhage. Techniques and precautions for the diagnosis and transcatheter therapy of hemobilia are discussed. (orig.)

  2. Prediction of Major Vascular Events after Stroke

    DEFF Research Database (Denmark)

    Ovbiagele, Bruce; Goldstein, Larry B.; Amarenco, Pierre

    2014-01-01

    BACKGROUND: Identifying patients with recent stroke or transient ischemic attack (TIA) at high risk of major vascular events (MVEs; stroke, myocardial infarction, or vascular death) may help optimize the intensity of secondary preventive interventions. We evaluated the relationships between...... the baseline Framingham Coronary Risk Score (FCRS) and a novel risk prediction model and with the occurrence of MVEs after stroke or TIA in subjects enrolled in the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial. METHODS: Data from the 4731 subjects enrolled in the SPARCL study...... were analyzed. Hazard ratios (HRs) from Cox regression models were used to determine the risk of subsequent MVEs based on the FCRS predicting 20% or more 10-year coronary heart disease risk. The novel risk model was derived based on multivariable modeling with backward selection. Model discrimination...

  3. Vascular lesions of the vocal fold.

    Science.gov (United States)

    Gökcan, Kürşat Mustafa; Dursun, Gürsel

    2009-04-01

    The aim of the study was to present symptoms, laryngological findings, clinical course, management modalities, and consequences of vascular lesions of vocal fold. This study examined 162 patients, the majority professional voice users, with vascular lesions regarding their presenting symptoms, laryngological findings, clinical courses and treatment results. The most common complaint was sudden hoarseness with hemorrhagic polyp. Microlaryngoscopic surgery was performed in 108 cases and the main indication of surgery was the presence of vocal fold mass or development of vocal polyp during clinical course. Cold microsurgery was utilized for removal of vocal fold masses and feeding vessels cauterized using low power, pulsed CO(2) laser. Acoustic analysis of patients revealed a significant improvement of jitter, shimmer and harmonics/noise ratio values after treatment. Depending on our clinical findings, we propose treatment algorithm where voice rest and behavioral therapy is the integral part and indications of surgery are individualized for each patient.

  4. De novo transcriptome analysis of pneumatophores (modified roots in the true mangrove species Avicennia marina and identification of the genes related to root gas exchange

    Directory of Open Access Journals (Sweden)

    Purushothaman Natarajan

    2017-10-01

    Full Text Available Mangroves plants which grow in estuaries naturally tolerate extreme conditions of high salinity (90 ppt and high light intensity. Avicennia marina is a true mangrove tree species with physiological adaptations like modified root system (pneumatophores and salt excretion glands in leaves as its one of the unique features to consider. The pneumatophores are a special type of roots with negative geotropism that project above the water surface or the level of flooded soils [1]. In contact with air these roots develop lenticels, which improve gas exchange between roots and environment [2]. In swamps and wetlands the presence of pneumatophores facilitates oxygen diffusion through the tissues, maintaining levels adequate for cellular respiration [3]. Objective of this study was to perform the whole transcriptome analysis of pneumatophore tissue of A. marina by Illumina sequencing and to identify putative genes involved in process of root gas exchange. We generated 19.73 million of paired-end reads and assembled into 86,856 unigenes with an average length of 772 bp. Further, annotation, tissue specific gene expression and genes related to root gas exchange will be presented.

  5. Voluntary exercise and green tea enhance the expression of genes related to energy utilization and attenuate metabolic syndrome in high fat fed mice.

    Science.gov (United States)

    Sae-Tan, Sudathip; Rogers, Connie J; Lambert, Joshua D

    2014-05-01

    Obesity and metabolic syndrome are growing public health problems. We investigated the effects of decaffeinated green tea extract (GTE) and voluntary running exercise (Ex) alone or in combination against obesity and metabolic syndrome in high fat (HF) fed C57BL/6J mice. After 16 wk, GTE + Ex treatment reduced final body mass (27.1% decrease) and total visceral fat mass (36.6% decrease) compared to HF-fed mice. GTE + Ex reduced fasting blood glucose (17% decrease), plasma insulin (65% decrease), and insulin resistance (65% decrease) compared to HF-fed mice. GTE or Ex alone had less significant effects. In the skeletal muscle, the combination of Ex and GTE increased the expression of peroxisome proliferator-activated receptor-γ coactivator-1α (Ppargc1a), mitochondrial NADH dehydrogenase 5 (mt-Nd5), mitochondrial cytochrome b (mt-Cytb), and mitochondrial cytochrome c oxidase III (mt-Co3). An increase in hepatic expression of peroxisome proliferator-activated receptor-α (Ppara) and liver carnitine palmitoyl transferase-1α (Cpt1a) and a decrease in hepatic expression of stearoyl-CoA desaturase 1 (Scd1) mRNA was observed in GTE + Ex mice. GTE + Ex was more effective than either treatment alone in reducing diet-induced obesity. These effects are due in part to modulation of genes related to energy metabolism and de novo lipogenesis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Effect of pollination and fertilization on the expression of genes related to floral transition, hormone synthesis and berry development in grapevine.

    Science.gov (United States)

    Dauelsberg, Patricia; Matus, José Tomás; Poupin, María Josefina; Leiva-Ampuero, Andrés; Godoy, Francisca; Vega, Andrea; Arce-Johnson, Patricio

    2011-09-15

    In the present work, the effect of assisted fertilization on anatomical, morphological and gene expression changes occurring in carpels and during early stages of berry development in Vitis vinifera were studied. Inflorescences were emasculated before capfall, immediately manually pollinated (EP) and fruit development was compared to emasculated but non-pollinated (ENP) and self-pollinated inflorescences (NESP). The diameter of berries derived from pollinated flowers (EP and NESP) was significantly higher than from non-pollinated flowers (ENP) at 21 days after emasculation/pollination (DAE), and a rapid increase in the size of the inner mesocarp, together with the presence of an embryo-like structure, were observed. The expression of gibberellin oxidases (GA20ox and GA2ox), anthranilate synthase (related to auxin synthesis) and cytokinin synthase coding genes was studied to assess the relationship between hormone synthesis and early berry development, while flower patterning genes were analyzed to describe floral transition. Significant expression changes were found for hormone-related genes, suggesting that their expression at early stages of berry development (13 DAE) is related to cell division and differentiation of mesocarp tissue at a later stage (21 DAE). Expression of hormone-related genes also correlates with the expression of VvHB13, a gene related to mesocarp expansion, and with an increased repression of floral patterning genes (PISTILLATA and TM6), which may contribute to prevent floral transition inhibiting fruit growth before fertilization takes place. Copyright © 2011 Elsevier GmbH. All rights reserved.

  7. Protein Kinase C Inhibitors as Modulators of Vascular Function and Their Application in Vascular Disease

    Directory of Open Access Journals (Sweden)

    Raouf A. Khalil

    2013-03-01

    Full Text Available Blood pressure (BP is regulated by multiple neuronal, hormonal, renal and vascular control mechanisms. Changes in signaling mechanisms in the endothelium, vascular smooth muscle (VSM and extracellular matrix cause alterations in vascular tone and blood vessel remodeling and may lead to persistent increases in vascular resistance and hypertension (HTN. In VSM, activation of surface receptors by vasoconstrictor stimuli causes an increase in intracellular free Ca2+ concentration ([Ca2+]i, which forms a complex with calmodulin, activates myosin light chain (MLC kinase and leads to MLC phosphorylation, actin-myosin interaction and VSM contraction. Vasoconstrictor agonists could also increase the production of diacylglycerol which activates protein kinase C (PKC. PKC is a family of Ca2+-dependent and Ca2+-independent isozymes that have different distributions in various blood vessels, and undergo translocation from the cytosol to the plasma membrane, cytoskeleton or the nucleus during cell activation. In VSM, PKC translocation to the cell surface may trigger a cascade of biochemical events leading to activation of mitogen-activated protein kinase (MAPK and MAPK kinase (MEK, a pathway that ultimately increases the myofilament force sensitivity to [Ca2+]i, and enhances actin-myosin interaction and VSM contraction. PKC translocation to the nucleus may induce transactivation of various genes and promote VSM growth and proliferation. PKC could also affect endothelium-derived relaxing and contracting factors as well as matrix metalloproteinases (MMPs in the extracellular matrix further affecting vascular reactivity and remodeling. In addition to vasoactive factors, reactive oxygen species, inflammatory cytokines and other metabolic factors could affect PKC activity. Increased PKC expression and activity have been observed in vascular disease and in certain forms of experimental and human HTN. Targeting of vascular PKC using PKC inhibitors may function in

  8. Improved vascularization of planar membrane diffusion devices following continuous infusion of vascular endothelial growth factor.

    Science.gov (United States)

    Trivedi, N; Steil, G M; Colton, C K; Bonner-Weir, S; Weir, G C

    2000-01-01

    Improving blood vessel formation around an immunobarrier device should improve the survival of the encapsulated tissue. In the present study we investigated the formation of new blood vessels around a planar membrane diffusion device (the Baxter Theracyte System) undergoing a continuous infusion of vascular endothelial growth factor through the membranes and into the surrounding tissue. Each device (20 microl) had both an inner immunoisolation membrane and an outer vascularizing membrane. Human recombinant vascular endothelial growth factor-165 was infused at 100 ng/day (low dose: n = 6) and 500 ng/day (high dose: n = 7) for 10 days into devices implanted s.c. in Sprague-Dawley rats; noninfused devices transplanted for an identical period were used as controls (n = 5). Two days following the termination of VEGF infusion, devices were loaded with 20 microl of Lispro insulin (1 U/kg) and the kinetics of insulin release from the lumen of the device was assessed. Devices were then explanted and the number of blood vessels (capillary and noncapillary) was quantified using morphometry. High-dose vascular endothelial growth factor infusion resulted in two- to threefold more blood vessels around the device than that obtained with the noninfused devices and devices infused with low-dose vascular endothelial growth factor. This increase in the number of blood vessels was accompanied by a modest increase in insulin diffusion from the device in the high-dose vascular endothelial growth factor infusion group. We conclude that vascular endothelial growth factor can be used to improve blood vessel formation adjacent to planar membrane diffusion devices.

  9. Exercise-mediated wall shear stress increases mitochondrial biogenesis in vascular endothelium.

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    Boa Kim

    Full Text Available Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs using in vitro and in vivo complementary studies.Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2 for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (ΔΨm. Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta and muscle feed (femoral artery arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds.Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function.

  10. Maternal exposure to cadmium during gestation perturbs the vascular system of the adult rat offspring

    International Nuclear Information System (INIS)

    Ronco, Ana Maria; Montenegro, Marcela; Castillo, Paula; Urrutia, Manuel; Saez, Daniel; Hirsch, Sandra; Zepeda, Ramiro; Llanos, Miguel N.

    2011-01-01

    Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remained unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-κB expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.

  11. NF1 Signal Transduction and Vascular Dysfunction

    Science.gov (United States)

    2015-05-01

    microenvironment that promotes much of the pathology associated with the disease . Moreover we hypothesize that a mechanistic consequence of the loss...obliteration of the normal red pulp architecture. In addition, we found significant peri-aveolar and peri-vascular inflammatory infiltrates in the lung...the mouse model of NF1 disease in the endothelium we proposed and have done experiments investigating the loss of endothelial NF1 in the adult

  12. Role of endovascular treatment in vascular injuries

    International Nuclear Information System (INIS)

    Tahir, M.M.; Haq, T.U.

    2012-01-01

    Objective: To evaluate retrospectively the results, complications and follow-up of patients after endovascular treatment of vascular injuries. Methods: Fifty transcatheter embolisation procedures (TCE) were performed in 46 patients between 1999 and 2008 at the Aga Khan University Hospital, Karachi. Injuries in 14 (30.4%) patients were due to road traffic accident; iatrogenic in 13 (28%); accidental in 6 (13%). Firearms, bomb blasts and earthquake contributed to injuries in 8(17%), 4(8.8%) and 1(2.2%) patients respectively. All patients underwent angiography and had evidence of either active haemorrhage, pseudo-aneurysm, abnormal vascularity or arteriovenous fistula. Follow-up ranged from 1 day to 6 years with mean of 10.5 months. Medical record files, lab results and imaging reports were utilised for the study. Procedure was declared as technically successful when there was cessation of extravasation, occlusion of fistula or exclusion of pseudo-aneurysm in the post-embolisation angiograms. Treatment was deemed clinically successful if there was resolution of the indication for which the procedure was done. Results: Transcatheter embolisation was technically successful in occluding vascular lesions in all 46 (100%) patients. Lesions recurred in 4 (9%) patients who underwent initially successful TCE. These patients were treated effectively with repeated TCE. Three patients died during the same hospital stay and 3 patients died after being discharged from the hospital. All these patients were treated successfully with TCE and had factors other then TCE contributing to their mortality. Conclusion: Transcatheter embolisation for vascular injuries was found to be a satisfactory procedure, with low morbidity and mortality rates. (author)

  13. Vascular access: the impact of ultrasonography

    Science.gov (United States)

    de Almeida, Carlos Eduardo Saldanha

    2016-01-01

    ABSTRACT Vascular punctures are often necessary in critically ill patients. They are secure, but not free of complications. Ultrasonography enhances safety of the procedure by decreasing puncture attempts, complications and costs. This study reviews important publications and the puncture technique using ultrasound, bringing part of the experience of the intensive care unit of the Hospital Israelita Albert Einstein, São Paulo (SP), Brazil, and discussing issues that should be considered in future studies. PMID:28076607

  14. Vascular Dysfunction in Horses with Endocrinopathic Laminitis.

    Directory of Open Access Journals (Sweden)

    Ruth A Morgan

    Full Text Available Endocrinopathic laminitis (EL is a vascular condition of the equine hoof resulting in severe lameness with both welfare and economic implications. EL occurs in association with equine metabolic syndrome and equine Cushing's disease. Vascular dysfunction, most commonly due to endothelial dysfunction, is associated with cardiovascular risk in people with metabolic syndrome and Cushing's syndrome. We tested the hypothesis that horses with EL have vascular, specifically endothelial, dysfunction. Healthy horses (n = 6 and horses with EL (n = 6 destined for euthanasia were recruited. We studied vessels from the hooves (laminar artery, laminar vein and the facial skin (facial skin arteries by small vessel wire myography. The response to vasoconstrictors phenylephrine (10-9-10-5M and 5-hydroxytryptamine (5HT; 10-9-10-5M and the vasodilator acetylcholine (10-9-10-5M was determined. In comparison with healthy controls, acetylcholine-induced relaxation was dramatically reduced in all intact vessels from horses with EL (% relaxation of healthy laminar arteries 323.5 ± 94.1% v EL 90.8 ± 4.4%, P = 0.01, laminar veins 129.4 ± 14.8% v EL 71.2 ± 4.1%, P = 0.005 and facial skin arteries 182.0 ± 40.7% v EL 91.4 ± 4.5%, P = 0.01. In addition, contractile responses to phenylephrine and 5HT were increased in intact laminar veins from horses with EL compared with healthy horses; these differences were endothelium-independent. Sensitivity to phenylephrine was reduced in intact laminar arteries (P = 0.006 and veins (P = 0.009 from horses with EL. Horses with EL exhibit significant vascular dysfunction in laminar vessels and in facial skin arteries. The systemic nature of the abnormalities suggest this dysfunction is associated with the underlying endocrinopathy and not local changes to the hoof.

  15. Role of vascular physiology in hyperthermia

    International Nuclear Information System (INIS)

    Song, C.W.

    1987-01-01

    The rate of blood supply to tumors significantly varies depending on the tumor type, site of tumor growth, and the stage of tumor growth. Even in the same tumor, blood flow is rather heterogeneous. The peripheral area of the tumors where the tissue pressure is relatively low is usually well perfused. Blood flow in the tumors may or may not be greater than that in the adjacent normal tissues. The response of newly formed tumor blood vessels to external stress, such as heat, it different from that in the normal tissues. Blood flow in the experimental rodent tumors initially increases up to twofold of control when heated at relatively low temperatures but tends to decrease when heated at temperatures above 42 0 -43 0 C. On the contrary, blood flow in the skin and muscle of rodents increases up to 20-fold before vascular damage occurs on heating at 43 0 -45 0 C. It thus appears that the vascular beds in tumors are more vulnerable to heat than those in normal tissues. Because of the large increase in blood flow in normal tissue on heating, heat dissipation by blood flow is usually greater in normal tissues than that in tumors during heating. Consequently, the temperature of tumors may rise higher than that in normal tissues. Preferential heating of tumors, however, may not be achieved all the time because the relative blood perfusion in some tumors or in parts of a tumor remains greater than that in the surrounding normal tissues. The intrinsically acidic intratumor environment becomes further acidic on heating owing to an increase in the synthesis of acidic metabolites and retarded removal of them as a result of heat-induced vascular damage. The intratumor environment also becomes hypoxic as a result of retardation of blood flow and vascular damage after heating

  16. Analgesics and sedatives in vascular interventionist radiologic

    International Nuclear Information System (INIS)

    Gregorio, M.A. de; Opta, J.M.; Pulido, J.M.; Encarnacion, C.E.; Arino, I., Fernandez, J.A.; Alfonso, E.R.

    1993-01-01

    Interventionist radiology routinely requires the use of different drugs (analgesics and sedatives) in the course of a procedure. Aside from their therapeutic action, these drugs can produce secondary or undesirable effects, making necessary an in-depth knowledge of them to assure their safe and efficient management. The aim of this work is to provide the vascular interventionist radiologist with additional information on the management of those drugs that contribute to minimizing patient discomfort and pain in interventionist procedures. Author

  17. Robotic vascular resections during Whipple procedure

    OpenAIRE

    Allan, Bassan J.; Novak, Stephanie M.; Hogg, Melissa E.; Zeh, Herbert J.

    2018-01-01

    Indications for resection of pancreatic cancers have evolved to include selected patients with involvement of peri-pancreatic vascular structures. Open Whipple procedures have been the standard approach for patients requiring reconstruction of the portal vein (PV) or superior mesenteric vein (SMV). Recently, high-volume centers are performing minimally invasive Whipple procedures with portovenous resections. Our institution has performed seventy robotic Whipple procedures with concomitant vas...

  18. Endothelial microparticles: Sophisticated vesicles modulating vascular function

    Science.gov (United States)

    Curtis, Anne M; Edelberg, Jay; Jonas, Rebecca; Rogers, Wade T; Moore, Jonni S; Syed, Wajihuddin; Mohler, Emile R

    2015-01-01

    Endothelial microparticles (EMPs) belong to a family of extracellular vesicles that are dynamic, mobile, biological effectors capable of mediating vascular physiology and function. The release of EMPs can impart autocrine and paracrine effects on target cells through surface interaction, cellular fusion, and, possibly, the delivery of intra-vesicular cargo. A greater understanding of the formation, composition, and function of EMPs will broaden our understanding of endothelial communication and may expose new pathways amenable for therapeutic manipulation. PMID:23892447

  19. New molecular probes of vascular inflammation

    International Nuclear Information System (INIS)

    Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (Department of Nuclear Medicine, University Hospital Münster, Münster, and DFG CRC 656 Molecular Cardiovascular Imaging, Westfälische Wilhelms University Münster, Münster, (Germany))" >VRACHIMIS, Alexis; HONOLD, Lisa; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >FAUST, Andreas; Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" data-affiliation=" (European Institute of Molecular Imaging, Westfälische Wilhelms University Münster, Münster, and DFG EXC 1003 Cells in Motion Cluster of Excellence, Westfälische Wilhelms University Münster, Münster, (Germany))" >HERMANN, Sven; SCHÄFERS, Michael

    2016-01-01

    New molecular imaging approaches featuring the assessment of inflammatory processes in the vascular wall on top of existing anatomic and functional vessel imaging procedures could emerge as decisive tools for the understanding and prevention of cardiovascular events. In this respect imaging approaches addressing specific molecular and cellular targets in atherosclerosis are of high interest. This review summarizes the rationale and current status of nuclear imaging probes which possess high translational potential.

  20. Early Vascular Ageing - A Concept in Development.

    Science.gov (United States)

    M Nilsson, Peter

    2015-04-01

    Cardiovascular disease (CVD) is a prevalent condition in the elderly, often associated with metabolic disturbance and type 2 diabetes. For a number of years, research dedicated to understand atherosclerosis dominated, and for many good reasons, this pathophysiological process being proximal to the CVD events. In recent years, research has been devoted to an earlier stage of vascular pathology named arteriosclerosis (arterial stiffness) and the new concept of early vascular ageing (EVA), developed by a group of mostly European researchers. This overview describes recent developments in research dedicated to EVA and new emerging aspects found in studies of families at high cardiovascular risk. There are new aspects related to genetics, telomere biology and the role of gut microbiota. However, there is still no unifying definition available of EVA and no direct treatment, but rather only recommendations for conventional cardiovascular risk factor control. New interventions are being developed - not only new antihypertensive drugs, but also new drugs for vascular protection - the selective angiotensin-II (AT2) agonist Compound 21 (C21). Human studies are eagerly awaited. Even new functional food products could have the potential to positively influence cardiometabolic regulation, to be confirmed.

  1. Altos custos financeiros do trauma vascular

    Directory of Open Access Journals (Sweden)

    Ricardo Costa-Val

    Full Text Available OBJETIVO: Demonstrar o custo e impacto financeiro referente à primeira abordagem cirúrgica das lesões vasculares em pacientes admitidos no Hospital João XXIII/FHEMIG, entre os anos de 2004 a 2006. MéTODOS: Trata-se de um estudo com aprovação ética, retrospectivo, de coorte e descritivo realizado a partir da auditoria de contas hospitalares referentes a 70 prontuários catalogados pelo Serviço de Trauma Cardiovascular. RESULTADOS: Cinco (7,14% prontuários foram excluídos por má qualidade técnica. O valor monetário repassado pelo Sistema Único de Saúde e pelo setor privado foram de R$ 103.614,96 (US$ 60.949,97 e de R$ 185.888,21 (US$ 109.346,0, respectivamente, implicando em defasagem potencial de 44%. Houve correlação direta entre custos e topografia anatômica das lesões e exponencial em relação às variáveis hemoderivados e próteses vasculares. CONCLUSÃO: Este estudo corrobora os altos custos do trauma vascular e fortalece a importância da auditoria de contas para as tomadas de decisões médicas.

  2. Pancreatic transplantation: Radiologic evaluation of vascular complications

    International Nuclear Information System (INIS)

    Snider, J.F.; Hunter, D.W.; Kuni, C.C.; Castaneda-Zuniga, W.R.; Letourneau, J.G.

    1991-01-01

    Transplantation of the pancreas is an increasingly common therapeutic option for preventing or delaying complications of type I diabetes mellitus. The authors studied the relative roles of various radiologic examinations in diagnosing vascular complications in these grafts including arterial and venous thrombosis, stenosis, and anastomotic leak (the most common vascular factors that necessitate pancreatectomy of the transplant), as defined with pathologic or arteriographic data. The results of 78 scintigraphic flow studies, 40 abdominal and pelvic computed tomographic (CT) scans, 27 sonograms, and eight color Doppler studies were evaluated in 52 patients who received a total of 27 cadaveric and 26 living-donor grafts over a 12-year period. These results were correlated with the data from 45 gross and microscopic pathologic studies and 37 arteriograms to determine their relative value in enabling detection of graft thrombosis and other vascular complications. Scintigraphy, CT, sonography, and color Doppler were all sensitive in detection of generalized graft abnormalities but lacked specificity in defining the underlying etiologic factors

  3. Pancreatic transplantation: Radiologic evaluation of vascular complications

    Energy Technology Data Exchange (ETDEWEB)

    Snider, J.F.; Hunter, D.W.; Kuni, C.C.; Castaneda-Zuniga, W.R.; Letourneau, J.G. (Univ. of Minnesota Hospital and Clinic, Minneapolis (USA))

    1991-03-01

    Transplantation of the pancreas is an increasingly common therapeutic option for preventing or delaying complications of type I diabetes mellitus. The authors studied the relative roles of various radiologic examinations in diagnosing vascular complications in these grafts including arterial and venous thrombosis, stenosis, and anastomotic leak (the most common vascular factors that necessitate pancreatectomy of the transplant), as defined with pathologic or arteriographic data. The results of 78 scintigraphic flow studies, 40 abdominal and pelvic computed tomographic (CT) scans, 27 sonograms, and eight color Doppler studies were evaluated in 52 patients who received a total of 27 cadaveric and 26 living-donor grafts over a 12-year period. These results were correlated with the data from 45 gross and microscopic pathologic studies and 37 arteriograms to determine their relative value in enabling detection of graft thrombosis and other vascular complications. Scintigraphy, CT, sonography, and color Doppler were all sensitive in detection of generalized graft abnormalities but lacked specificity in defining the underlying etiologic factors.

  4. Arterial vascularization of the pineal gland.

    Science.gov (United States)

    Kahilogullari, Gokmen; Ugur, Hasan Caglar; Comert, Ayhan; Brohi, Recep Ali; Ozgural, Onur; Ozdemir, Mevci; Karahan, Suleyman Tuna

    2013-10-01

    The arterial vascularization of the pineal gland (PG) remains a debatable subject. This study aims to provide detailed information about the arterial vascularization of the PG. Thirty adult human brains were obtained from routine autopsies. Cerebral arteries were separately cannulated and injected with colored latex. The dissections were carried out using a surgical microscope. The diameters of the branches supplying the PG at their origin and vascularization areas of the branches of the arteries were investigated. The main artery of the PG was the lateral pineal artery, and it originated from the posterior circulation. The other arteries included the medial pineal artery from the posterior circulation and the rostral pineal artery mainly from the anterior circulation. Posteromedial choroidal artery was an important artery that branched to the PG. The arterial supply to the PG was studied comprehensively considering the debate and inadequacy of previously published studies on this issue available in the literature. This anatomical knowledge may be helpful for surgical treatment of pathologies of the PG, especially in children who develop more pathology in this region than adults.

  5. VASCULAR REMODELING IN HYPERTENSION: ANGIOGENESIS FEATURES

    Directory of Open Access Journals (Sweden)

    L. A. Haisheva

    2014-07-01

    Full Text Available Aim — cross-sectional study of changes in various segments of the vascular bed in arterial hypertension (AH, defining the role of inducers and inhibitors of angiogenesis in these processes.Materials and methods. The study included 99 patients with arterial hypertension of I–II degree, average age of 63.2 ± 2.6 years, diseaseduration 9.2 ± 7.2 years.Results. It was found that patients with arterial hypertension have disorders in all segments of vascular bed: endothelial dysfunction (highvWF, microcirculatory disorders, and increased pulse wave velocity (PWV of elastic-type vessels. The level of angioginesis factors doesnot depend on such parameters as gender, age, body mass index. Smoking and duration of hypertension influence on vascular endothelialgrowth factor raise and endostatin levels are higher in patients with family history of cardiovascular diseases. Duration of disease is directlycorrelated with microcirculatory disorders and the PWV, correlation between microcirculatory disorders and pulse wave velocity indicatetheir common processes.

  6. Amplatzer vascular plugs in congenital cardiovascular malformations

    International Nuclear Information System (INIS)

    Barwad, Parag; Ramakrishnan, Sivasubramanian; Kothari, Shyam S; Saxena, Anita; Gupta, Saurabh K; Juneja, Rajnish; Gulati, Gurpreet Singh; Jagia, Priya; Sharma, Sanjiv

    2013-01-01

    Amplatzer vascular plugs (AVPs) are devices ideally suited to close medium-to-large vascular communications. There is limited published literature regarding the utility of AVPs in congenital cardiovascular malformations (CCVMs). To describe the use of AVPs in different CCVMs and to evaluate their safety and efficacy. All patients who required an AVP for the closure of CCVM were included in this retrospective review of our catheterization laboratory data. The efficacy and safety of AVPs are reported. A total of 39 AVPs were implanted in 31 patients. Thirteen (33%) were AVP type I and 23 (59%) were AVP type II. AVP type III were implanted in two patients and type IV in one patient. The major indications for their use included closure of pulmonary arteriovenous malformation (AVM) (n = 7), aortopulmonary collaterals (n = 7), closure of a patent Blalock-Taussig shunt (n = 5), systemic AVM (n = 5), coronary AVM (n = 4), patent ductus arteriosus (PDA) (n = 3), pulmonary artery aneurysms (n = 3), and venovenous collaterals (n = 2). Deployment of the AVP was done predominantly via the 5 – 7F Judkin's right coronary guide catheter. Overall 92% of the AVPs could be successfully deployed and resulted in occlusion of the target vessel in all cases, within 10 minutes. No procedure-related or access site complication occurred. AVPs are versatile, easy to use, and effective devices to occlude the vascular communications in a variety of settings. AVP II is especially useful in the closure of tubular structures with a high flow

  7. Vascular development in the vertebrate pancreas

    Science.gov (United States)

    Azizoglu, D. Berfin; Chong, Diana C.; Villasenor, Alethia; Magenheim, Judith; Barry, David M.; Lee, Simon; Marty-Santos, Leilani; Fu, Stephen; Dor, Yuval; Cleaver, Ondine

    2016-01-01

    The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. PMID:27789228

  8. Vascularized nerve grafts: an experimental study.

    Science.gov (United States)

    Donzelli, Renato; Capone, Crescenzo; Sgulò, Francesco Giovanni; Mariniello, Giuseppe; Maiuri, Francesco

    2016-08-01

    The aim of this study is to define an experimental model in order to promote the functional recovery of the nerves using grafts with vascular support (Vascular Nerve Grafts - VNG). The aim of this study is to define, on an experimental model in normal recipient bed, whether the functional recovery with VNG is superior to that obtained non-vascularized graft (NNG). Twenty male rabbits, which underwent dissection of sciatic nerve, were later treated by reinnervation through an autograft. In 10 animals the reconstruction of sciatic nerve was realized with VNG; in 10 control animals the reconstruction of sciatic nerve was realized with NNG. The VNG group showed a better axonal organization and a significantly higher number of regenerated axons in the early phases (after 30 days) than the NNG group, whereas the difference in the axonal number at day 90 was less significant; besides, the axon diameter and the myelin thickness were not significantly improved by VNG group. Our data suggests that the use of VNG leads to a faster regeneration process and a better functional recovery, although the final results are comparable to those of the NNG. VNG improve the quality of the axonal regeneration (axonal diameter and Schwann cells), although the increase in the axonal number is not significant and does not improve the long-term functional outcome.

  9. Vascular nitric oxide: Beyond eNOS

    Directory of Open Access Journals (Sweden)

    Yingzi Zhao

    2015-10-01

    Full Text Available As the first discovered gaseous signaling molecule, nitric oxide (NO affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC to produce cyclic guanosine monophosphate (cGMP, although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA or production of cyclic inosine monophosphate (cIMP] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis.

  10. Vascular development in the vertebrate pancreas.

    Science.gov (United States)

    Azizoglu, D Berfin; Chong, Diana C; Villasenor, Alethia; Magenheim, Judith; Barry, David M; Lee, Simon; Marty-Santos, Leilani; Fu, Stephen; Dor, Yuval; Cleaver, Ondine

    2016-12-01

    The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Electrotonic vascular signal conduction and nephron synchronization

    DEFF Research Database (Denmark)

    Marsh, D.J.; Toma, I.; Sosnovtseva, Olga

    2009-01-01

    Marsh DJ, Toma I, Sosnovtseva OV, Peti-Peterdi J, Holstein-Rathlou NH. Electrotonic vascular signal conduction and nephron synchronization. Am J Physiol Renal Physiol 296: F751-F761, 2009. First published December 30, 2008; doi:10.1152/ajprenal.90669.2008.-Tubuloglomerular feedback (TGF) and the ......Marsh DJ, Toma I, Sosnovtseva OV, Peti-Peterdi J, Holstein-Rathlou NH. Electrotonic vascular signal conduction and nephron synchronization. Am J Physiol Renal Physiol 296: F751-F761, 2009. First published December 30, 2008; doi:10.1152/ajprenal.90669.2008.-Tubuloglomerular feedback (TGF......) and the myogenic mechanism control afferent arteriolar diameter in each nephron and regulate blood flow. Both mechanisms generate self-sustained oscillations, the oscillations interact, TGF modulates the frequency and amplitude of the myogenic oscillation, and the oscillations synchronize; a 5: 1 frequency ratio...... is the most frequent. TGF oscillations synchronize in nephron pairs supplied from a common cortical radial artery, as do myogenic oscillations. We propose that electrotonic vascular signal propagation from one juxtaglomerular apparatus interacts with similar signals from other nephrons to produce...

  12. Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

    Science.gov (United States)

    Atchison, Elizabeth A; Garrity, James A; Castillo, Francisco; Engman, Steven J; Couch, Steven M; Salomão, Diva R

    2016-01-01

    Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. A total of 52 patients who underwent removal of vascular orbital lesions. The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). The existence and pattern of staining with VEGF and its subtypes on these lesions. There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. Retinal vascular segmentation using superpixel-based line operator and its application to vascular topology estimation.

    Science.gov (United States)

    Na, Tong; Xie, Jianyang; Zhao, Yitian; Zhao, Yifan; Liu, Yue; Wang, Yongtian; Liu, Jiang

    2018-05-09

    Automatic methods of analyzing of retinal vascular networks, such as retinal blood vessel detection, vascular network topology estimation, and arteries/veins classification are of great assistance to the ophthalmologist in terms of diagnosis and treatment of a wide spectrum of diseases. We propose a new framework for precisely segmenting retinal vasculatures, constructing retinal vascular network topology, and separating the arteries and veins. A nonlocal total variation inspired Retinex model is employed to remove the image intensity inhomogeneities and relatively poor contrast. For better generalizability and segmentation performance, a superpixel-based line operator is proposed as to distinguish between lines and the edges, thus allowing more tolerance in the position of the respective contours. The concept of dominant sets clustering is adopted to estimate retinal vessel topology and classify the vessel network into arteries and veins. The proposed segmentation method yields competitive results on three public data sets (STARE, DRIVE, and IOSTAR), and it has superior performance when compared with unsupervised segmentation methods, with accuracy of 0.954, 0.957, and 0.964, respectively. The topology estimation approach has been applied to five public databases (DRIVE,STARE, INSPIRE, IOSTAR, and VICAVR) and achieved high accuracy of 0.830, 0.910, 0.915, 0.928, and 0.889, respectively. The accuracies of arteries/veins classification based on the estimated vascular topology on three public databases (INSPIRE, DRIVE and VICAVR) are 0.90.9, 0.910, and 0.907, respectively. The experimental results show that the proposed framework has effectively addressed crossover problem, a bottleneck issue in segmentation and vascular topology reconstruction. The vascular topology information significantly improves the accuracy on arteries/veins classification. © 2018 American Association of Physicists in Medicine.

  14. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    Science.gov (United States)

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  15. Embryonic exposure to cis-bifenthrin enantioselectively induces the transcription of genes related to oxidative stress, apoptosis and immunotoxicity in zebrafish (Danio rerio).

    Science.gov (United States)

    Jin, Yuanxiang; Pan, Xiuhong; Cao, Limin; Ma, Bufang; Fu, Zhengwei

    2013-02-01

    Cis-bifenthrin (cis-BF) is used widely for agricultural and non-agricultural purpose. Thus, cis-BF is one of the most frequently detected insecticides in the aquatic ecosystem. As a chiral pesticide, the commercial cis-BF contained two enantiomers including 1R-cis-BF and 1S-cis-BF. However, the difference in inducing oxidative stress, apoptosis and immunotoxicity by the two enantiomers in zebrafish still remains unclear. In the present study, the zebrafish were exposed to environmental concentrations of cis-BF, 1R-cis-BF and 1S-cis-BF during the embryos developmental stage. We observed that the mRNA levels of the most genes related to oxidative stress, apoptosis and immunotoxicity including Cu/Zn-superoxide dismutase (Cu/Zn-Sod), catalase (Cat), P53, murine double minute 2 (Mdm2), B-cell lymphoma/leukaemia-2 gene (Bcl2), Bcl2 associated X protein (Bax), apoptotic protease activating factor-1 (Apaf1), Caspase 9 (Cas9), Caspase 3 (Cas3), interleukin-1 beta (IL-1β) and interleukin-8(Il-8) were much higher in 1S-cis-BF treated group than those in cis-BF or 1R-cis-BF treated ones, suggesting that 1S-cis-BF has higher risk to induced oxidative stress, apoptosis and immunotoxicity than 1R-cis-BF in zebrafish. The information presented in this study will help with elucidating the differences and environmental risk of the two enantiomers of cis-BF-induced toxicity in aquatic organisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Determination of the frequency of polymorphisms in genes related to the genome stability maintenance of the population residing at Monte Alegre, PA (Brazil) municipality

    International Nuclear Information System (INIS)

    Hozumi, Cristiny Gomes

    2010-01-01

    The human exposure to ionizing radiation coming from natural sources is an inherent feature of human life on earth, for man and all living things have always been exposed to these sources. Ionizing radiation is a known genotoxic agent which can affect the genomic stability and genes related to DNA repair may play a role when they have committed certain polymorphism. This study aimed to analyze the frequency of polymorphisms (SNPs) in genes of DNA repair and cell cycle control: hOGG1 (Ser326Cys), XRCC3 (Thr241 Met) and p53 (Arg72Pro) in saliva samples from a population located Monte Alegre, state of Para were collected in August 2008 and 40 samples of men and 46 samples of women, adding a total of 86 samples. By RFLP was determined the frequency of homozygous genotypes and / or heterozygous for polymorphic genes. The I)OGG1 gene was 5% of the allele 326Cys, XRCC3 gene found about 21 % of the allele 241 Met and p53 gene showed 40.8% of the 72Pro allele. And the genotype frequencies of individuals for the three genes were 91.04%, 88.06% and 59.7% for homozygous wild genotype, 5.97%, 11.94% and 22.39% for heterozygote genotype and 2,99%, zero and 17:91% for homozygous polymorphic hOGG1 genes respectively, XRCC3, p53. These values are similar to those found in previous studies. The influence of these polymorphisms, which are involved in DNA repair and consequent genotoxicity induced by radiation depends on dose and exposure factors such as smoking, which is statistically a factor in public health surveillance in the region. This study gathered information and molecular epidemiology in Monte Alegre, that help to characterization of local population. (author)

  17. Revascularization of diaphyseal bone segments by vascular bundle implantation.

    Science.gov (United States)

    Nagi, O N

    2005-11-01

    Vascularized bone transfer is an effective, established treatment for avascular necrosis and atrophic or infected nonunions. However, limited donor sites and technical difficulty limit its application. Vascular bundle transplantation may provide an alternative. However, even if vascular ingrowth is presumed to occur in such situations, its extent in aiding revascularization for ultimate graft incorporation is not well understood. A rabbit tibia model was used to study and compare vascularized, segmental, diaphyseal, nonvascularized conventional, and vascular bundle-implanted grafts with a combination of angiographic, radiographic, histopathologic, and bone scanning techniques. Complete graft incorporation in conventional grafts was observed at 6 months, whereas it was 8 to 12 weeks with either of the vascularized grafts. The pattern of radionuclide uptake and the duration of graft incorporation between vascular segmental bone grafts (with intact endosteal blood supply) and vascular bundle-implanted segmental grafts were similar. A vascular bundle implanted in the recipient bone was found to anastomose extensively with the intraosseous circulation at 6 weeks. Effective revascularization of bone could be seen when a simple vascular bundle was introduced into a segment of bone deprived of its normal blood supply. This simple technique offers promise for improvement of bone graft survival in clinical circumstances.

  18. Vascular Variations Associated with Intracranial Aneurysms.

    Science.gov (United States)

    Orakdogen, Metin; Emon, Selin Tural; Somay, Hakan; Engin, Taner; Is, Merih; Hakan, Tayfun

    2017-01-01

    To investigate the vascular variations in patients with intracranial aneurysm in circle of Willis. We used the data on 128 consecutive intracranial aneurysm cases. Cerebral angiography images were analyzed retrospectively. Arteries were grouped as anterior cerebral arterial system (ACS), posterior cerebral arterial system (PCS) and middle cerebral arterial system (MCS) for grouping vascular variations. Lateralization, being single/multiple, gender; and also any connection with accompanying aneurysms" number, localization, dimension, whether bleeding/incidental aneurysm has been inspected. Variations were demonstrated in 57.8% of the cases. The most common variation was A1 variation (34.4%). The rate of variations was 36.7%, 24.2% and 10.2% respectively in ACS, PCS and MCS. MCS variations were significantly higher in males. Anterior communicating artery (ACoA) aneurysm observance rates were significantly higher and posterior communicating artery (PCoA) aneurysm and middle cerebral artery (MCA) aneurysm observance rates were significantly lower when compared to "no ACS variation detected" cases. In "PCS variation detected" cases, PCoA aneurysm observance rates and coexistence of multiple variations were significantly higher. The rate of vascular variations in patients with aneurysms was 57.8%. Arterial hypoplasia and aplasia were the most common variations. ACS was the most common region that variations were located in; they were mostly detected on the right side. Coexistence of ACoA aneurysm was higher than PCoA and MCA aneurysms. In the PCS variations group, PCoA aneurysms were the most common aneurysms that accompanying the variation and multiple variations were more common than in the other two groups. The variations in MCS were most common in males.

  19. T cells in vascular inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Lucas L Lintermans

    2014-10-01

    Full Text Available Inflammation of the human vasculature is a manifestation of many different diseases ranging from systemic autoimmune diseases to chronic inflammatory diseases, in which multiple types of immune cells are involved. For both autoimmune diseases and chronic inflammatory diseases several observations support a key role for T lymphocytes in these disease pathologies, but the underlying mechanisms are poorly understood. Previous studies in several autoimmune diseases have demonstrated a significant role for a specific subset of CD4+ T cells termed effector memory T cells. This expanded population of effector memory T cells may contribute to tissue injury and disease progression. These cells exert multiple pro-inflammatory functions through the release of effector cytokines. Many of these cytokines have been detected in the inflammatory lesions and participate in the vasculitic reaction, contributing to recruitment of macrophages, neutrophils, dendritic cells, NK cells, B cells and T cells. In addition, functional impairment of regulatory T cells paralyzes anti-inflammatory effects in vasculitic disorders. Interestingly, activation of effector memory T cells in uniquely dependent on the voltage-gated Kv1.3 potassium channel providing an anchor for specific drug targeting. In this review, we focus on the CD4+ T cells in the context of vascular inflammation and describe the evidence supporting the role of different T cell subsets in vascular inflammation. Selective targeting of pathogenic effector memory T cells might enable a more tailored therapeutic approach that avoids unwanted adverse side effects of generalized immunosuppression by modulating the effector functions of T cell responses to inhibit the development of vascular inflammation.

  20. Extraglandular and intraglandular vascularization of canine prostate.

    Science.gov (United States)

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism. Copyright 2004 Wiley-Liss, Inc.