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Sample records for calcitonin gene-related peptide

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    Calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) are potent vasorelaxant peptides. This study examined exercise-induced changes in CGRP and AM levels in 12 healthy sea level natives at sea level (SL) and subsequently after 24 h (HA1) and 5 days (HA5) in high altitude hypoxia (4559 m......). Plasma values of CGRP, AM, calcitonin, noradrenaline, adrenaline, lactate and heart rate were measured at rest and during maximal exercise (W(max)). On each study day, the dopamine D(2)-receptor antagonist, domperidone (30 mg; n=6), or no medication (n=6) was given 1 h before exercise. W(max) at SL, HA1...

  2. Calcitonin gene-related peptide and migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Ashina, Messoud

    2014-01-01

    levels of CGRP in MA patients are comparable to MO, but CGRP levels varied among studies. A number of animal studies, including knock-ins of familial hemiplegic migraine (FHM) genes, have examined the relationship between CGRP and cortical spreading depression. In patients, CGRP does not trigger migraine......BACKGROUND: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathophysiology. Most studies have focused on CGRP in relation to migraine without aura (MO). About one-third of migraine patients have attacks with aura (MA), and this is a systematic review of the current literature...... in FHM, but is a robust trigger of migraine-like headache both in MA and MO patients. The treatment effect of CGRP antagonists are well proven in the treatment of migraine, but no studies have studied the effect specifically in MA patients. CONCLUSION: This systematic review indicates that the role...

  3. Involvement of calcitonin gene-related peptide in migraine

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2000-02-18

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M. Ashina

    2002-01-01

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

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

    OpenAIRE

    Brodda Jansen, Gunilla

    1996-01-01

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

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

    DEFF Research Database (Denmark)

    Lind, H; Edvinsson, L

    2002-01-01

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

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

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression....... The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model...

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    .58). Headache severity and intensity were not different between the groups. Conclusions: Familial hemiplegic migraine ( FHM) patients do not show hypersensitivity of the calcitonin gene-related peptide (CGRP)-cyclic adenosine 3 ', 5 '-monophosphate pathway, as characteristically seen in migraine patients......Objective: The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine...... with aura associated with several gene mutations. FHM shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. We tested the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype. Methods: We included 9 FHM patients with known...

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

    OpenAIRE

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Hauge, Anne Werner; Olesen, Jes;

    2010-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Changma Fu; Zongsheng Yin; Defu Yu; Zuhua Yang

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zhenghui Wang

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    OpenAIRE

    Lenz, H. J.; Brown, M R

    1990-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Noormohammad Noori

    2015-06-01

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

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

    Science.gov (United States)

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

    2015-11-01

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

  5. 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.

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

    OpenAIRE

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

    1991-01-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers...... intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via...

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

    Institute of Scientific and Technical Information of China (English)

    Jixiang Cui; Peng Qu; Chunping Qiao

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    J.A. Fischer

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are...... potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels....... potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ω-conotoxin GVIA inhibited the potassium induced CGRP release significantly...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are...... potassium releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels....... potassium induced CGRP release. In the absence of calcium ions (Ca2+) and in the presence of a cocktail of blockers, the stimulated CGRP release from dura mater was reduced almost to the same level as basal CGRP release. In the TG ¿-conotoxin GVIA inhibited the potassium induced CGRP release significantly...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine...

  17. 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...

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

    Directory of Open Access Journals (Sweden)

    Patrícia Severo do Nascimento

    2012-09-01

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

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

    OpenAIRE

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

    1988-01-01

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

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

    Science.gov (United States)

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

    2010-04-01

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

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

    Science.gov (United States)

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

    2016-07-22

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-03-01

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

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

    王宁; 顾锡镇; 邓颖; 张南军; 谈友芬; 蔡新; 王丽珠

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

    Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM). The study revealed an extensive innervation of the mammary nipples, in which CGRP-immunoreactive (IR) nerve fibres were abundantly present in the epidermis, dermal connective tissue and intralobular connective tissue of the mammary....... The location of SP-IR appeared to be comparable to CGRP-IR, but in fewer fibres. Dense NPY-IR networks of nerve fibres were closely associated with the fascicles of smooth musculature in the core of the nipple base. In contrast, VIP-IR fibres were only sparsely present, and SOM-IR was not detected...

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

    Science.gov (United States)

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

    2002-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wang Xiaocheng

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

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

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    唐江琼; 秦旭平

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Rui Ling; Jun Yi; Ling Wang; Mofan Ning

    2006-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND AND AIM: Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene......-related peptide (CGRP) systems on the GTN-induced neuronal activation in this model. MATERIALS AND METHODS: The femoral vein was catheterised in rats and GTN was infused (4 µg/kg/min, for 20 minutes, intravenously). Immunohistochemistry was performed to analyse Fos, nNOS and CGRP and Western blot for measuring n......NOS protein expression. The effect of olcegepant, L-nitro-arginine methyl ester (L-NAME) and neurokinin (NK)-1 receptor antagonist L-733060 were analysed on Fos activation. RESULTS: GTN-treated rats showed a significant increase of nNOS and CGRP in dura mater and CGRP in the trigeminal nucleus caudalis (TNC...

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

    Science.gov (United States)

    Durham, Paul L

    2016-08-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Longju Chen; Peijun Wang; Feng Li; Wutian Wu

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2014-07-30

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

    catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; p< 0.05) and inversely related to plasma adrenaline levels (r=-0.......53; p<0.02) but positively related to circulating levels of CGRP (r=0.58; p<0.01). No significant relation was found for plasma noradrenaline, renin activity, or endothelin-1. COMP(art) was positively related to plasma volume (r=0.50; p<0.02) and inversely to systemic vascular resistance (r=-0.69; p<0.......001) and central circulation time (r=-0.49; p<0.02). During oxygen inhalation, COMP(art) decreased (-13%; p<0.005) and systemic vascular resistance increased (+10%; p<0.001) towards normal values without significant changes in mean arterial pressure. Plasma adrenaline (-16%; p<0.01) decreased and the...

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

    Directory of Open Access Journals (Sweden)

    Max D. Kauther, Jie Xu, Christian Wedemeyer

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marcin Magierowski

    2014-03-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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.

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

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    Jerzy Kaleczyc

    2010-11-01

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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    J.P. Damico

    2012-10-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2010-01-01

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

  17. Effects of tegaserod on Fos,substance P and calcitonin gene-related peptide expression induced by colon inflammation in lumbarsacral spinal cord

    Institute of Scientific and Technical Information of China (English)

    Yi-Ning Sun; Jin-Yan Luo

    2004-01-01

    AIM: To investigate the mechanisms of tegaserod, a partial 5-HT4 agonist, in reducing visceral sensitivity by observing Fos, substance P (SP) and calcitonin gene-related peptide (CGRP) expression in the lumbarsacral spinal cord inducedby colonic inflammation in rats.METHODS: Twenty-four male rats with colonic inflammation induced by intraluminal instillation of trinitrobenzenesulfonic acid (TNBS) were divided into 3 groups. Treatment group Treatment group 2: intra-gastric administration of tegaserod,saline, 2.0 mL/d. After 7 d of intra-gastric administration,lumbarsacral spinal cord was removed and processed for Fos, SP and CGRP immunohistochemistry.RESULTS: In rats of the control group, the majority of Fos labeled neurons was localized in deeper laminae of the lumbarsacral spinal cord (L5-S1). SP and CGRP were primarily expressed in the superficial laminae of the spinal cord after TNBS injection. Intra-gastric administration of tegaserod neurons (22.0±7.7) and SP density (12.5±1.4) in the dorsal horn in the lumbarsacral spinal cord compared to those of the control group (62.2±18.9, 35.9±8.9, P<0.05). However,CGRP content in dorsal horn did not significantly reduce in rats of treatment group 1 (1.2±1.1) compared to that of the control group (2.8±2.4, P>0.05). Neither Fos expression nor SP or CGRP density in the dorsal horn significantly declined in rats of treatment group 2 compared to those of the control group (P>0.05).CONCLUSION: Tegaserod can significantly reduce Fos labeled neurons in the lumbarsacral spinal cord induced by colonic inflammation. Tegaserod may reduce visceral sensitivity by inhibiting SP expression in the dorsal horn of spinal cord.

  18. Effects of Qindan Capsule(芩丹胶囊) on Blood Pressure,Endothelin, Calcitonin Gene-related Peptide and Angiotensin-Ⅱ in Spontaneous Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To observe the hypotensive effects of Qindan Capsule (芩丹胶囊, QC) on spontaneous hypertensive rats (SHR) and its effect on the contents of endothelin (ET), calcitonin gene-related peptide (CGRP) and angiotensin-Ⅱ (Ang-Ⅱ ) in plasma and vascular tissues, and to investigate the possible mechanism of QC in lowering blood pressure. Methods: Forty SHRs were divided into 5 groups: the high dosage QC group [QCHD, 750 mg/(kg·d)], the low dosage QC group [QCLD, 150 mg/(kg·d)], the Niuhuang Jiangya Pill group [牛黄降压丸, NJP, 200 mg/(kg·d)], the Captopril group [ 15 mg/(kg·d)]and the model group, 8 in each group. Meanwhile, a normal control group consisting of 8 Wistar-Kyoto (WKY) rats was set up also. All the rats were administered with medicine through gastrogavage. Systolic blood pressure (SBP),level of ET, CGRP and Ang-Ⅱ in plasma and Ang-Ⅱ in tissues of mesenteric artery were detected in all the rats after 12 weeks of treatment. Results: The level of SBP after treatment in the QCHD group was lower than that in the model group ( P<0.01 ), but with no significant difference as compared with that in the Captopril group and the NJP group (P>0.05). After treatment, the plasma level of ET was lower and CGRP higher than those in the model group (both P<0.05), and also higher than those in the NJP and Captopril group (both P<0.05). As for the content of Ang- Ⅱ, in mesenteric arterial tissues, it was lower in the QCHD group than that in the model group ( P<0.05), but in plasma, it showed no significant difference between the two groups (P>0.05). Conclusion: QC has a satisfactory hypotensive action on SHR rats, and its mechanism may be associated with the regulation on plasma vasoactive peptide and regional renin-angiotensin system.

  19. Effect of calcitonin gene related peptide regulated nuclear factor kappa B signal transduction on c-kit+ cardiac stem cells in hypoxia state

    Directory of Open Access Journals (Sweden)

    Xian-ping LONG

    2015-11-01

    Full Text Available Objective To investigate the effects of calcitonin gene-related peptide (CGRP on the apoptosis of c-kit+ cardiac stem cells in hypoxia. Methods Ischemia and hypoxia models of c-kit+ cardiac stem cells were reproduced in vitro. The models were divided into hypoxia+CGRP group, hypoxia+CGRP8-37 (antagonist of CGRP group, hypoxia control group, normal oxygen group, and hypoxia+BAY11-7082 [antagonist of nuclear factor kappa B (NF-κB] group. NF-κB translocation after hypoxia was detected by immunofluorescence, and NF-κB channel proteins were determined with Western blotting. The NF-κB translocation and the expression of NF-κB channel proteins after CGRP intervention were detected, and the cell apoptosis rate after intervention was determined with flow cytometry in each group. Results Under hypoxia the NF-κB signal pathway was activated, and nuclear translocation occurred in NF-κBP65 (red fluorescence. Compared with hypoxia control group, the expressions of NF-κB related proteins such as P-I-κB, NF-κBP65 and NF-κBP50 decreased obviously (P<0.05. Compared with the hypoxia+CGRP group, the expressions of NF-κB related proteins increased significantly (P<0.05 as mentioned above in hypoxia+CGRP8-37 group. Both the early and late apoptotic rates declined in hypoxia+CGRP group compared with that of hypoxia control group (P<0.05, however, the early apoptotic rate increased markedly in hypoxia+CGRP8-37 group as compared with that of hypoxia+CGRP group (P<0.05. Conclusion Under hypoxia, CGRP may regulate the NF-κB signal pathway, and at the same time suppress the apoptosis of c-kit+ cardiac stem cells. DOI: 10.11855/j.issn.0577-7402.2015.10.03

  20. Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guangshun Zheng; Yongjie Yang; Xiubin Fang

    2006-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied.OBJECTIVE:To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion.DESIGN: Randomized controlled animal study.SETTING:Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University.MATERIALS:A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA),and NGF (1 × 106 U/L, 0.5 mL, Siweite Company, Dalian).METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to duly 20055. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1 ×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham

  1. Levels of vasoactive intestinal peptide,cholecystokinin and calcitonin gene-related peptide in plasma and jejunum of rats following traumatic brain injury and underlying significance in gastrointestinal dysfunction

    Institute of Scientific and Technical Information of China (English)

    Chun-Hua Hang; Ji-Xin Shi; Jie-Shou Li; Wei Wu; Wei-Qin Li; Hong-Xia Yin

    2004-01-01

    AIM: To study the alterations of brain-gut peptides following traumatic brain injury (TBI) and to explore the underlying significance of these peptides in the complicated gastrointestinal dysfunction.METHODS: Rat models of focal traumatic brain injury were established by impact insult method, and divided into 6 groups (6 rats each group) including control group with sham operation and TBI groups at postinjury 3, 12, 24, 72 h, and d 7. Blood and proximal jejunum samples were taken at time point of each group and gross observations of gastrointestinal pathology were recorded simultaneously. The levels of vasoactive intestinal peptide (VIP) in plasma, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK) in both plasma and jejunum were measured by enzyme immunoassay (EIA). Radioimmunoassay (RIA) was used to determine the levels of VTP in jejunum. RESULTS: Gastric distension, delayed gastric emptying and intestinal dilatation with a large amount of yellowish effusion and thin edematous wall were found in TBI rats through 12 h and 72 h, which peaked at postinjury 72 h. As compared with that of control group (247.8±29.5 ng/L), plasma VIP levels were significantly decreased at postinjury 3, 12 and 24 h (106.7±34.1 ng/L, 148.7±22.8 ng/L, 132.8±21.6 ng/L,respectively), but significantly increased at 72 h (405.0±29.8 ng/L) and markedly declined on d 7 (130.7±19.3 ng/L).However, Plasma levels CCK and CGRP were significantly increased through 3 h and 7 d following TBT (126-691% increases), with the peak at 72 h. Compared with control (VIP, 13.6±1.4 ng/g; CGRP, 70.6±17.7 ng/g); VIP and CGRP levels in jejunum were significantly increased at 3 h after TBI (VIP, 35.4±5.0 ng/g; CGRP, 103.8±22.1 ng/g), anddeclined gradually at 12 h and 24 h (VIP, 16.5±1.8 ng/g, 5.5±1.4 ng/g; CGRP, 34.9±9.7 ng/g, 18.5±7.7 ng/g), but were significantly increased again at 72 h (VIP, 48.7±9.5 ng/g; CGRP, 142.1±24.3 ng/g), then declined in various degrees on d 7 (VIP, 3.8±1

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

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2011-01-01

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

  3. Effects of alpha-calcitonin gene-related peptide on osteoprotegerin and receptor activator of nuclear factor-κB ligand expression in MG-63 osteoblast-like cells exposed to polyethylene particles

    Directory of Open Access Journals (Sweden)

    Kauther Max D

    2010-11-01

    Full Text Available Abstract Background Recent studies demonstrated an impact of the nervous system on particle-induced osteolysis, the major cause of aseptic loosening of joint replacements. Methods In this study of MG-63 osteoblast-like cells we analyzed the influence of ultra-high molecular weight polyethylene (UHMWPE particles and the neurotransmitter alpha-calcitonin gene-related peptide (CGRP on the osteoprotegerin/receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factorκB (OPG/RANKL/RANK system. MG-63 cells were stimulated by different UHMWPE particle concentrations (1:100, 1:500 and different doses of alpha-CGRP (10-7 M, 10-9 M, 10-11 M. RANKL and OPG mRNA expression and protein levels were measured by RT-PCR and Western blot. Results Increasing particle concentrations caused an up-regulation of RANKL after 72 hours. Alpha-CGRP showed a dose-independent depressive effect on particle-induced expression of RANKL mRNA in both cell-particle ratios. RANKL gene transcripts were significantly (P -7 M lead to an up-regulation of OPG protein. Conclusion In conclusion, a possible osteoprotective influence of the neurotransmitter alpha-CGRP on particle stimulated osteoblast-like cells could be shown. Alpha-CGRP might be important for bone metabolism under conditions of particle-induced osteolysis.

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

    Institute of Scientific and Technical Information of China (English)

    苏珂; 龙艳; 胡永玲

    2000-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    赵波; 吕云利; 姚向荣; 廖军

    2012-01-01

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

  6. Inhibition of calcitonin gene-related peptide and insulin-like growth factor: a potential new therapeutic strategy to reduce bone pain in bone metastases of breast cancer%抑制降钙基因相关肽和胰岛素样生长因子:一种减轻乳腺癌骨转移患者骨痛的新策略

    Institute of Scientific and Technical Information of China (English)

    梁燕

    2010-01-01

    @@ 2009年圣·安东尼奥会议上,Teruhisa Sakurai等作了题名为"Inhibition of calcitonin gene-related peptide and insulin-like growth factor:a potential new therapeutic strategy to reduce bone pain in bone metastases of breastcancer"的报告.

  7. 支气管哮喘患儿不同治疗方法内皮素和降钙素基因相关肽结果比较%Study of endothelin and calcitonin gene-related peptide levels in children with bronchial asthma by different therapies

    Institute of Scientific and Technical Information of China (English)

    吕汉文; 卢远达; 徐淑兰; 叶彩丽; 林灿华; 周翔

    2002-01-01

    Background: Bronchial asthma is an allergic pulmonary disease. The attack is mostly induced by the inhalation of or contact with allergens, such as pollens, dusts, insects (such as mite), germs, etc. During the attack, patients have severe dyspnea which is due to spasm of bronchial smooth muscles, swelling of the bronchial mucosa, and hypersecretion of the mucus, leading to bronchial obstruction. To observe the endothelin(ET) and calcitonin gene related peptide(CGRP) changes in treating children with bronchial asthma by dopamine( DP), dobutamine( DOB),and regitine.

  8. Influence of Buyang Huanwu Decoction on Endothelin and Calcitonin Gene-related Peptide in Patients with Migraine%补阳还五汤对偏头痛患者血浆CGRP和ET的影响

    Institute of Scientific and Technical Information of China (English)

    张洪涛; 张淑玲

    2013-01-01

    目的:观察补阳还五汤对偏头痛患者血浆降钙素基因相关肽(CGRP)和内皮素(ET)的影响.方法:72例偏头痛患者随机分为两组,西药组36例,口服尼莫地平20~40 mg,每日3次;急性发作期加服麦角胺咖啡因片1~2片/次.中药组36例,给予补阳还五汤,每日1剂,水煎分早晚服.两组均连续治疗3个月.治疗前、后监测偏头痛发作频率、持续时间、严重程度、药物的不良反应、CGRP和ET的水平,并与36例正常人对照.结果:中药组的总有效率显著高于西药组(P<0.05);两组偏头痛患者均较正常人ET明显增高(均P<0.01),CGRP明显降低(均P<0.01);西药组和中药组均可降低ET水平、偏头痛积分,提高CGRP水平(均P<0.01),但中药组比西药组作用更明显(均P<0.01).服用补阳还五汤未发生明显的不良的反应.结论:补阳还五汤能通过调节血管活性物质CGRP,ET水平,改善血管的异常舒缩状况,从而达到缓解偏头痛的作用.%Objective: To observe the influence of Buyang Huanwu decoction on endothelin (ET) and calcitonin gene-related peptide (CGRP) in patients with migraine. Method: Seventy two patients with migraine were divided into 2 groups randomly, 36 patients in western medicine group were treated by Nimodipine tablets 20-40 mg once, 3 times a day, To add ergotamine caffeine 1-2 tablets once in acute seizure phase. 36 patients in Chinese medicine group were treated by Buyang Huanwu decoction, take a decoction a day, divided into morning and evening. Patients had received continuous treatment for three months. Migraine frequency, duration, severity, adverse drug reactions and the concentration of plasma CGRP and ET were monitored before and after treatment. And comparative study with 36 cases of normal. Result: The total efficiency of traditional Chinese medicine group was significantly higher than that of the western medicine group (P < 0. 05 ) ; ET in patients with migraine was significantly

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

    DEFF Research Database (Denmark)

    Edvinsson, Lars

    2007-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    林立; 张强; 曾晓立; 张凯; 王林

    2001-01-01

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

  11. 降钙素基因相关肽和BIBN4096BS对麻醉大鼠心肌缺血的作用%Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats

    Institute of Scientific and Technical Information of China (English)

    Dong-Mei WU; Pieter A van ZWIETEN; Henri N DOODS

    2001-01-01

    AIM: The cardioprotective effect of calcitonin gene related peptide (CGRP) was investigated in an ischemia rat model. METHODS: Ischemia-reperfusion injury was provoked by 60 min left main coronary artery occlu sion followed by 60 min of reperfusion in anesthetized rats. The transverse slices of ventricles were stained by 2,3,5-triphenyltetrazolium chloride to determine the in farct area. Plasma creatine phosphokinase levels were determined by means of a creatine phosphokinase (CPK) kit. A radioimmunoassay was used to determine plasma CGRP levels. RESULTS: Intravenous infusion of CGRP (1 nmol· kg- 1·h-1) 10 min before occlusion until the end of reperfusion reduced infarct size by 89 % ± 5 %. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase. Infusion of the same dose of CGRP commehcing from the start of reperfusion until its end induced a 40 % ± 3 % reduction of the infarct size. The cardioprotective effects of CGRP were blocked by the novel CGRP antagonist BIBN4096BS (20 nmol· kg-1 · h-1 ). Although cardiac ischemia resulted in an almost 50 % increase in plasma CGRP levels in blood sampled from right cardiac ventri cle, intravenous infusion of the CGRP antagonist BIBN4096BS before occlusion until the end of reperfusion had no statistically significant effect on the infarct size. CONCLUSION: The present study demonstrates that CGRP is a potent myocardial protective substance.

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

    Institute of Scientific and Technical Information of China (English)

    邱恩超; 于生元; 李凤鹏; 刘若卓; 石宏; 景向红

    2014-01-01

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

  13. 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.

  14. The protective effect of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats%大鼠脑缺血再灌注后降钙素基因相关肽对受损胃黏膜的保护作用

    Institute of Scientific and Technical Information of China (English)

    冯国营; 许晓博; 王迁

    2009-01-01

    @@ The purpose of the present study is to investigate the protective effect of calcitonin gene-related pepfide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting.

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

    Institute of Scientific and Technical Information of China (English)

    顾炳权; 秦明; 黄裕新; 刘树林

    2002-01-01

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

  16. Calcitonin Gene-Related Peptide and Migraine: Implications for Therapy

    NARCIS (Netherlands)

    U. Arulmani (Udayasankar)

    2004-01-01

    textabstractIt is clearly evident from the literature that headache has troubled mankind from the dawn of civilization (Rapoport & Edmeads, 2000). A variety of methods have been used throughout the ages in an attempt to alleviate or cure this pain; these may have been the most appropriate at that

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  18. 普瑞巴林对原发性三叉神经痛患者血浆 P物质和降钙素基因相关肽的影响%Influence of Pregabalin on plasma substance P and calcitonin gene-related peptide in patients with trigeminal neuralgia

    Institute of Scientific and Technical Information of China (English)

    熊勋波; 杨涛; 邓刚; 成祥林; 向明清; 刘焰

    2014-01-01

    目的::观察普瑞巴林( PGB )和卡马西平( CBZ )对原发性三叉神经痛( PTN )患者血浆 P 物质( SP )和降钙素基因相关肽( CGRP)以及疼痛视觉模拟评分( VAS)的影响,评估PGB治疗PTN的疗效和安全性。方法:130例PTN患者随机分为观察组64例使用PGB治疗,对照组66例使用CBZ治疗。分别从低剂量开始给药,观察患者的疗效及不良反应至第4周末,两组患者在治疗前和结束时以放免法测定血浆SP和CGRP含量,并进行VAS评分。结果:观察组患者的总有效率89.1%,对照组72.1%,两组患者差异有统计学意义(P<0.05);治疗后两组患者的血浆SP和CGRP均下降,观察组患者较对照组尤为明显(P<0.05)。观察组不良反应发生率31.3%明显低于对照组59.1%。结论:PGB治疗PTN疗效和安全性均高于CBZ。%Objective:To observe influence of Pregabalin ( PGB) and Carbamazepine ( CBZ) on plasma substance P ( SP) , calcitonin gene-related peptide ( CGRP) , and pain visual analogue score ( VAS) for patients with trigeminal neuralgia ( PTN) , and e﹣valuate efficacy and safety of PGB in treatment of PTN. Methods:130 patients with PTN were randomly divided into observation group ( PGB, 64 cases) and control group ( CBZ, 66 cases) . Both groups were administered with low dose at first, and then the therapeutic effect and adverse effect until termination of the fourth week were observed. The plasma SP and CGRP were detected by radioimmuno﹣assay before and after the treatment, while the visual analogue scales ( VAS) were measured. Results:The clinical efficiency of PGB was 89. 1%, that of CBZ was 72. 1%, and there was a significant difference between the two groups (P<0. 05). The treatments re﹣duced plasma SP and CGRP levels in both groups, and the change of PGB group was more obvious than that of CBZ group (P<0. 05). The incidence rate of adverse effect by PGB (31. 3%) was less than that by CBZ (59. 1%) (P<0. 05). Conclusions

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

    Institute of Scientific and Technical Information of China (English)

    司马蕾; 刘波涛; 厉建春; 刘乃刚; 张韫

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  1. Peptídeo relacionado ao gene da calcitonina por iontoforese na viabilidade de retalho cutâneo randômico em ratos Calcitonin gene-related peptide by iontophoresis on the viability of the randon skin flaps in rats

    Directory of Open Access Journals (Sweden)

    Ivaldo Esteves Junior

    2004-12-01

    Full Text Available Objetivo: Investigar o efeito da administração tópica do peptídeo relacionado ao gene da calcitonina (CGRP por iontoforese na viabilidade de retalho cutâneo randômico em ratos. Métodos: Sessenta ratos Wistar EPM-1, adultos e machos foram submetidos a retalho cutâneo randômico. Os animais foram distribuídos aleatoriamente em quatro grupos. Nos animais do grupo 1 (controle, n=15 realizou-se simulação de estímulo elétrico, no grupo 2 (iontoforese placebo, n=15 os animais foram submetidos à corrente contínua, no grupo 3 (controle de absorção, n=15 os animais receberam simulação de estímulo elétrico com CGRP e, por fim os animais do grupo 4 (tratado, n=15 foram tratados com iontoforese de CGRP. Em todos os grupos estes procedimentos foram realizados imediatamente após a técnica operatória e nos dois dias subsequentes. A porcentagem da área de necrose foi avaliada no sétimo dia de pós-operatório. Resultados: A média das porcentagens das áreas de necrose foram: grupo 1- 48%, grupo 2 - 51%, grupo 3 - 46% e, grupo 4 - 28%. A análise estatística, através do teste de Kruskal-Wallis, evidenciou diferença significante (pPurpose: Assess the effect of the local administration of calcitonin gene-related peptide (CGRP by iontophoresis on the viability of random skin flap in rats. Methods: Sixty Wistar-EPM 1 rats were submitted to dorsal skin flap of cranial base 10 x 4 cm with interposition of a plastic barrier between the skin flap and the donnor site. The animals were randomly distributed in four groups (n = 15 in each group and were treated as follows: in group 1 (control, animals were submitted to a simulation of electrical current for 20 minutes; group 2, (iontophoresis placebo animals were submitted to direct current of 4mA amplitude for 20 minutes; group 3 (absorption control receive simulation of electrical current for 20 minutes with CGRP on one of the electrodes; group 4 (iontophoretically treated treated by

  2. Effects of xenotransplantation of microencapsulated sciatic nerve tissue cells on the expression of calcitonin gene-related peptide after spinal cord injury in rats%异种细胞移植对大鼠损伤脊髓降钙素基因相关肽表达的影响

    Institute of Scientific and Technical Information of China (English)

    段平国; 孙贵才; 刘德明

    2011-01-01

    Objective: To observe the effects of xenotransplantation of the microencapsulated sciatic nerve tissue/cella on the expression of calcitonin gene-related peptide (CGRP) after spinal cord injury (SCI) in rats.Methods: Bilateral sciatic nerves of rabbits were preconditioned for 1 week were dissected under sterile conditions and made into nerve tissue/cells suspension which was mixed with 1.5% sodium alginate solution.The mixture was then extruded using a droplet generation device into 20 mmol/L barium chloride solution to form barium-alginate capsules.Microencapsulated nerve tissue/cells suspension was implanted into the injured sites of the spinal cord in rats.By immunohistochernstry, the expressions of CGRP were observed.Results: The number of CGRP-positive cells in the right ventral horn of spinal cord of rats reduced remarkably in each group after SCI, and it gradually recovered in varying degrees 1 week later.The difference of the number of CGRP-positive cells between the microcapsule group and the cell group was not remarkable, but both of them existed in the distinction when compared with the injury group (P <0.05).At 2, 4 weeks and 8 weeks after SCI, compared to the cell group and injury group,the number of CGRP-positive cells in the microcapsule group increased obviotrsly.Conclusion: The xenotransplantation of the microencapsulated sciatic nerve tissue/cells promotes the expression of CGRP after SCI in rats, benefiting the regeneration of neuron.%目的:观察微囊化异种坐骨神经组织细胞移植对脊髓损伤大鼠降钙素基因相关肽(CGRP)表达的影响.方法:取家兔预变性处理1周的坐骨神经制成组织细胞悬液,与1.5%海藻酸钠溶液混合并喷入20mmol/L氯化钡溶液中制成微囊化的组织细胞悬液.将其植入SD大鼠脊髓损伤处,通过免疫组织化学显色观察CGRP的表达情况.结果:SCI后各组大鼠右侧脊髓前角CGRP阳性细胞数减少,1周后均不同程度地逐渐恢复.SCI后1周,细

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

    Institute of Scientific and Technical Information of China (English)

    王义生; 皮国富; 王亚寒; 赵国强; 李月白

    2012-01-01

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

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

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    王飞; 张慧宇; 窦予昕; 李适廷; 张纲; 谭颖徽

    2016-01-01

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

  5. 神经肽P物质、降钙素基因相关肽在膝骨性关节炎软骨下骨中的表达%Neuropeptides substance P and calcitonin gene related peptide expression in knee osteoarthritis ;subchondral bone

    Institute of Scientific and Technical Information of China (English)

    付昌马; 杨祖华

    2014-01-01

    Objective To study the expression of neuropeptide substance P (SP) and calcitonin gene related peptide (CGRP) in the subchondral bone patients with knee osteoarthritis (OA). Methods A total 40 patients with OA were used as study group, and 10 patients with lower femur fractures were used as control group. Immunohistochemical staining were used to analyze neuropeptides SP and CGRP positive expression in 40 cases OA patients and 10 cases lower femur fractures patients. Results (1) The number of neuropeptide SP positive cells (2.62±0.31 vs. 1.58±0.32, P<0.05) and neuropeptide CGRP positive cells (2.58±0.23 vs. 1.55±0.25, P<0.05) was significantly higher in OA group than control group. (2) Neuropeptide SP average optical density(0.345±0.031 vs. 0.224±0.072, P<0.05) and neuropeptide CGRP average optical density(0.585±0.043 vs. 0.326±0.065, P<0.05) was significantly higher in OA group than control group. (3) Neuropeptide CGRP average optical density (0.585±0.043) was higher than the average optical density of SP (0.345±0.031) (P<0.05) in OA group. Conclusion Significantly higher neuropeptide SP and CGRP levels were found in patients with OA;neuropeptide expression leading to bone metabolic imbalance, adjustment disorder with cycles occur within the joint, and thus play a role in OA group.%目的:研究证明含有神经肽 P 物质(SP)、降钙素基因相关肽(CGRP)共同存在于膝骨性关节炎(OA)中,本研究验证这些肽能神经在膝OA发病中可能起作用。探讨膝OA患者软骨下骨中神经肽SP、 CGRP的表达及临床意义。方法收集2010年4月至2013年9月在合肥市第三人民医院治疗的40例膝OA患者及10例股骨下段骨折患者临床资料。免疫组化染色检测40例膝OA患者(OA组)及10例股骨下段骨折患者(正常对照组)软骨下骨组织神经肽SP、 CGRP的阳性表达。结果(1)40例膝OA患者与10例正常对照组比较,神经肽SP的阳性细胞表达数(2.62

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

    Institute of Scientific and Technical Information of China (English)

    丁继固; 茹立强

    2005-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    陈璐; 赵鑫; 郭政

    2014-01-01

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

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

    Science.gov (United States)

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

    2008-08-01

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

  9. 受体成分蛋白在降钙素基因相关肽和血管紧张素Ⅱ对血管平滑肌细胞血管过氧化物酶1表达调控中的作用%Involvement of the receptor component protein in the regulation of vascular peroxidase-1 expression induced by calcitonin gene-related peptide and angiotensin Ⅱ in vascular smooth muscle cell

    Institute of Scientific and Technical Information of China (English)

    刘彦梅; 彭虹艳; 郭锋; 全海燕; 骆镜妃; 秦旭平

    2015-01-01

    血管紧张素Ⅱ (angiotensin Ⅱ,Ang Ⅱ)和降钙素基因相关肽(calcitonin gene-related peptide,CGRP)在血管的损伤和保护中起重要作用.为了探讨CGRP受体成分蛋白(receptor component protein,RCP)在CGRP和Ang Ⅱ对血管平滑肌细胞(vascularsmooth muscle cell,VSMC)血管过氧化物酶1(vascular peroxidase-1,VPO1)表达调控中的作用及机制,本研究采用体外培养鼠源性Al0血管平滑肌细胞株(A10VSMC),给予CGRP或/和Ang Ⅱ刺激,并用小干扰RNA (siRNA)干扰细胞RCP基因的表达,Western Blot检测RCP以及VPO1蛋白表达水平;RT-PCR检测RCP及VPO1 mRNA的表达水平.结果显示,在静止期野生型A10VSMC,CGRP和Ang Ⅱ能分别上调RCP和VPO1蛋白和mRNA表达(均P<0.05),但CGRP预孵育细胞后,Ang Ⅱ诱导的RCP和VPO1蛋白表达降低(均P<0.05);与野生型组比较,VPO1在所有RCP基因干扰组的表达均显著降低(均P<0.01).同时,在RCP基因干扰条件下,和对照组相比,CGRP处理组VPO1蛋白的表达显著增加,而Ang Ⅱ组没有明显变化;和Ang Ⅱ1组相比,CGRP与Ang Ⅱ联合作用显著增加VPOl蛋白表达,但这种作用能被抗氧化酶Catalase所抑制(P<0.05).以上结果提示,RCP可能参与CGRP或Ang Ⅱ诱导的VPO1蛋白表达;RCP可能在介导CGRP和Ang Ⅱ受体共同调控VPO1表达的信号转导整合中起一定作用.

  10. Distribution and source of calcitonin gene-related peptide immunoreactive nerve terminal in prepuce of penis and frenulum of prepuce of rats%大鼠阴茎包皮及包皮系带内降钙素基因相关肽免疫阳性神经末梢的分布与起源

    Institute of Scientific and Technical Information of China (English)

    吴仲敏; 王东红; 赵礼东; 凌树才; 朱晞

    2006-01-01

    树枝状或念珠状分布,大多成束走行,长短不一,有的呈结节状膨大.②阴茎系带处降钙素基因相关肽免疫阳性神经末梢的分布密度明显大于阴茎包皮处(2.15±0.32,1.02±0.22,t=-2.03,P<0.01).③结合荧光金逆行标记法研究发现,这些神经末梢起源于第6腰髓对应的背根神经节和第1骶髓对应的背根神经节的神经元.荧光金逆标阳性神经元大小不等,胞体呈圆形或卵圆形,未见明显的突起,胞浆内有明亮的金黄色细小颗粒,胞核无标记.细胞大多沿神经束成行排列或散在分布.进一步作降钙素基因相关肽免疫荧光标记后发现降钙素基因相关肽单标阳性神经元大多为中小型细胞,染色较深,反应产物均匀分布于胞浆内,呈明亮的深绿色(FITC标记色).在不同激发光下对照观察同一张阳性切片,发现荧光金/降钙素基因相关肽双标阳性细胞均为中小型,其数量占荧光金逆行标记阳性细胞总数的二分之一.结论:降钙素基因相关肽可能参与大鼠阴茎包皮以及包皮系带感觉信息的传递.大鼠阴茎包皮系带内降钙素基因相关肽免疫阳性神经末梢源自于第6腰髓对应的背根神经节和第1骶髓对应的背根神经节的神经元.%BACKGROUND: Frenulum of prepuce of penis contained many nerve terminals is an extremely sensitive region. If the frenulum is injured in circumcision or other operations, the complication, such as postoperative spontaneous pain of penis, sexual disturbance and so on, will occur. But there still is no define explanation for this up to now.OBJECTIVE: To observe the distribution of immunoreactive nerve terminal of calcitonin gene-related peptide (CGRP) in prepuce of penis and frenulum of prepuce of adult SD rats, and look for the source of CGRP immunoreactive nerve terminal in frenulum of prepuce.DESIGN: A single sample trial.SETTING:Department of Anatomy, School of Medicine, Zhejiang University.MATERIALS: The

  11. 电刺激大鼠上矢状窦区硬脑膜后血浆与脑组织中降钙素基因相关肽、P物质和前列腺素 E2释放差异%Release difference of calcitonin gene-related peptide,substance P and prostaglandin E2 in orbital venous plexus plasma and brain tissues from rats with dura mater of superior sagittal sinus following electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    陈健; 吕新勇; 孙晓萍; 陈春苗; 周军; 王振中; 萧伟

    2014-01-01

    OBJECTIVE Toexplorethefeasibilityofpreparingamigrainemodelusingratdura materofsuperiorsagittalsinusinfollowingelectricalstimulation.METHODS MaleSDratswereexposed to 1 h electrical stimulation after brain electrode implantation,at 3 V,6 Hz,and a pulse of 0.25 ms.At 0, 1 5,30 min,and 1 h,orbital blood and brain tissue were taken.The content of calcitonin gene-related peptide (CGRP),substance P and prostaglandin E2 (PGE2 )in the plas ma and brain tissue was detec-tedbyradioimmunoassay.RESULTS ThebraintissuecontentofCGRP,substancePandPGE2in the sham group and normal group was not significantly different.CGRP,substance P and PGE2 in brain tissue of model group were 3.41 ±0.93,1 .80 ±0.64,3.41 ±0.93 and (1 .80 ±0.64)ng·g -1 respec-tively,significantly different from sham group(P<0.05).At different time points,the content of CGRP, substance P and PGE2 in plasma orbital venous plexus showed no significant difference between sham groupandmodelgroup.CONCLUSION ThereleaseofCGRP,PGE2andsubstancePinbraintissue is significantly different fro m that of plas ma after electrical sti mulation.The results suggest that a model of migraine can be constructed by electrical stimulation.%目的:探讨电刺激大鼠上矢状窦区硬脑膜制备偏头痛模型的可行性。方法雄性SD 大鼠,脑部电极植入术后行电压3 V、频率6 Hz、脉宽0.25 ms、时间1 h电刺激,并于刺激0,15和30 min和1 h进行眼眶采血,采血后取脑组织。采用放射免疫法检测血浆和脑组织中降钙素基因相关肽(CGRP)、P物质和前列腺素E2(PGE2)含量。结果手术对照组与正常对照组大鼠脑组织中 CGRP 含量、P 物质含量和PGE2含量为均无显著性差异;模型组大鼠脑组织中CGRP、P物质和 PGE2分别为3.41±0.93,1.80±0.64和(5.17±0.69)ng·g -1,与手术对照组大鼠相比均有显著性差异(P<0.05)。各时间点手术对照组与模型组大鼠外周

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

    OpenAIRE

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

    2006-01-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  14. 降钙素基因相关肽调控细胞外信号调节激酶减轻高体积分数氧对胎鼠肺泡Ⅱ型上皮细胞的损伤作用%Damage - Reduced Effects of Calcitonin Gene - Related Peptide on Hyperoxia - Exposed Type Ⅱ Alveolar Epithelial Cell Mediated by Extracellular Signal -Regulated Kinase

    Institute of Scientific and Technical Information of China (English)

    付红敏; 李利; 汤春辉; 皇甫春荣; 米弘瑛; 李献珍; 方芳; 许峰

    2012-01-01

    Objective To explore the effects of calcitonin gene - related peptide( CGRF) on type II alveolar epithelial cell( AEC II ) exposed to hyperoxia and whether the mechanism is mediated by extracellular signal - regulated kinase ( ERK) pathway. Methods AEC II were isolated from 21 d fetal rat lung and grew for 12 h to attach. Then AEC II were randomly divided into six groups;air group,CGRP/air group,CGRP8 -37/air group,hyperoxia group,CGRP/O2 and CGRP8 - 37/O2 group. Air or hyperoxia environment was achieved by exposing AEC1I into 210 mL · L-1oxygen or 850 mL · L-1 oxygen for 18 h. CGRP group or CGRP8 - 37 group was carried out by adding 10-1 mol · L-1 CGRP or both CGRP and CGRP8 -37(10-1 mol · L-1) ,a receptor antagonist against CGRP,into medium before cultured in air or 850 mL · I-1 oxygen. Lactate dehydrogenase (LDH) ,alkaline phosphatase (AKP) and malondialdehyde (MDA) were measured by immune tur-bidimetry and reactive oxygen species( ROS) by flow cytometry. Immunofluorescence microscopy was used to analyze the expression of surfactant protein C( SP - C) and Western blot was taken to detect the content of p - ERK1/2. Results The levels of MDA,LDH,AKP,ROS and p-ERKl/2 were markedly increased in hyperoxia group than those in air group [(2. 29 ±0.10) μmol · L-1 vs (1.06±0.14) μmol · L-1, (58.79 ±5.01) U ·L-1 vs (25.92 ±3.68) U · L-1,(24.63 ±2.92) U · L-1 vs (10. 34 ±1.78) U · L-1,47.74 ±3.35 vs 25.96 ±5.04, 1.21 ±0.06 vs 0.45 ±0.05 ,P, <0.01] .whereas expression of SP -C was decreased in hyperoxia group compared with air group (22.75 ±3.31 vs 43. 50 ± 4.42 ). Levels of MDA, LDH, AKP and ROS were reduced with an elevated expression of p - ERK1 /2 and SP - C in CGRP/O2 group compared with those in hyperoxia group and CGRP8 - 37/O2 group (Pa < 0. 01). There were no significant differences about the levels of MDA,LDH,AKP,ROS and SP- C among three groups cultured in air condition. The expression of p - ERK1/2 in CGRP/air group was also higher than

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

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Calcitoningene relatedpeptide(CGRP)enco dedbythecalcitoningeneandcomposedof37ami noacidisabiologicallyactivepolypeptidedetected usinggeneticrecombinationbyRosenfeldin1983.ThemRNAtranscriptedfromcalcitoningenewas translatedintotheCGRPprecursorof128amino acidstoredinthecellularsecretorygranules,then theprecursorwasconvertedenzymaticallyinto CGRPof37aminoacidtoexertitsbiological effect[1].CGRPiswidelydistributedintheperiph eralandcentralnervoussystem,whichsuggestsdi versebiologicalfunctionssuchastheneuralregul...

  16. Blockade of calcitonin gene-related peptide release after superior sagittal sinus stimulation in cat

    DEFF Research Database (Denmark)

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

    1999-01-01

    . Avitriptan and CP122,288 both have strong binding affinities for 5HT(1B/1D)receptors, but only CP122,288 is a potent inhibitor of PPE. In this study we sought to compare the effects of CP122,288 and avitriptan on jugular vein CGRP release after stimulation of the superior sagittal sinus (SSS) in the cat....... In eleven anaesthetized cats external jugular vein blood samples were analyzed by radioimmunoassay for CGRP levels in three settings: a) control, b) 1 min after SSS stimulation and c) 1 min after SSS stimulation in presence of drug. Stimulation of the SSS resulted in release of CGRP from the external...

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

  18. Intermedin and calcitonin gene-related peptide fail to shine in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    K.W. Morrice

    2014-11-01

    Methods and results: 81 patients admitted with suspected ACS were enrolled into the study. 50 were confirmed ACS by ACC (2000 guidelines and 31 were in a control group as non-cardiac chest pain. Intermedin was non-significantly elevated 6.14 pg/ml vs 4.84 pg/ml 8 h after pain onset. The degree of elevation will have limited clinical applicability.

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

    Science.gov (United States)

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

    2012-01-11

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

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  1. Possible sites of action of the new calcitonin gene-related peptide receptor antagonists

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2010-01-01

    synapses CGRP results in vasodilatation via receptors on the smooth muscle cells. At central synapses, CGRP acts postjunctionally on second-order neurons to transmit pain centrally via the brainstem and midbrain to higher cortical pain regions. The recently developed CGRP-receptor antagonists have...

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

    Science.gov (United States)

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

    2003-01-27

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  9. The role of calcium in endotoxin-induced release of calcitonin gene-related peptide (CGRP) from rat spinal cord

    Institute of Scientific and Technical Information of China (English)

    唐跃明; 韩启德; 王宪

    1997-01-01

    In the present study, the role of calcium in endotoxin-induced CGRP release was studied. 2 .5-50 μg/mL endotoxin and 1 -10 mmol/L caffeine caused concentration-dependent increase of CGRP release from rat spinal cord in vitro. However, no additive effect could he found when caffeine and endotoxin were concomitantly incubated. By using capsaicin, Ca2+-free medium, Omega-Conotoxin, nifedipine, W-7, ryanodine, MgCl2, Tris-ATP, rutheni-um red, the results indicate that the release of CGRP evoked by endotoxin from the sensory fibers of rat spinal cord is dependent on extracellular calcium. After entering into the cell through the N-type calcium channel, calcium binds to calmodulin, and triggers calcium release from intracellular calcium store by activating the caffeine-sensitive but ryan-odine-insensitive mechanism.

  10. Sumatriptan does not change calcitonin gene-related peptide in the cephalic and extracephalic circulation in healthy volunteers

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Petersen, Jesper; Wienecke, Troels;

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Acylation of peptide drugs with fatty acid chains has proven beneficial for prolonging systemic circulation, as well as increasing enzymatic stability and interactions with lipid cell membranes. Thus, acylation offers several potential benefits for oral delivery of therapeutic peptides, and we hy...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-09-01

    In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery. PMID:24599901

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

    Institute of Scientific and Technical Information of China (English)

    颜玲; 陈合新; 邵正仁

    2009-01-01

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

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

    DEFF Research Database (Denmark)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  18. 4991W93 inhibits release of calcitonin gene-related peptide in the cat but only at doses with 5HT(1B/1D) receptor agonist activity?

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-15

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

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

    Directory of Open Access Journals (Sweden)

    M. Sheykhzade

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  4. Intermolecular interactions between salmon calcitonin, hyaluronate, and chitosan and their impact on the process of formation and properties of peptide-loaded nanoparticles.

    Science.gov (United States)

    Umerska, Anita; Corrigan, Owen I; Tajber, Lidia

    2014-12-30

    The principal aim of this work was to study the formulation of a ternary complex comprising salmon calcitonin (sCT), hyaluronate (HA), and chitosan (CS) in a nanoparticle (NP) format. As interactions between the constituents are possible, their presence and component mass mixing ratio (MMR) and charge mixing ratio (CMR) were investigated to tune the properties of NPs. Intermolecular interactions between sCT and HA as well as sCT and CS were studied by infrared spectroscopy (FTIR) and dynamic viscosity. The impact of MMR, CMR, and HA molecular weight on the sCT loading capacity in NPs and in vitro release properties was determined. sCT complexes to HA via electrostatic interactions and a support for hydrophobic interactions between sCT and HA as well as sCT and CS was found by FTIR. The sCT/HA complex is soluble but, depending on the mass mixing ratio between sCT and HA, NPs and microparticles were also formed indicative of associative phase separation between HA and sCT. The negatively charged HA/CS/sCT NPs were characterized by very high values (above 90%) of peptide association for the systems tested. Also, high sCT loading up to 50% were achieved. The peptide loading capacity and in vitro release properties were dependent on the NP composition. The zeta potential of the NPs without sCT was negative and ranging from -136 to -36 mV, but increased to -84 to -19 mV when the peptide was loaded. The particle size was found to be smaller and ranging 150-230 nm for sCT/NPs in comparison to NPs without sCT (170-260 nm). Short-term storage studies in liquid dispersions showed that the colloidal stability of NPs was acceptable and no release of sCT was observed for up to 3 days. In conclusion, a range of NP systems comprising sCT, HA, and CS was successfully developed and characterized. Such NPs may be considered as a suitable nanoparticulate format for the delivery of sCT. PMID:25447822

  5. Calcitonin Salmon Nasal Spray

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2015-01-01

    An MS/MS based analytical strategy was followed to solve the complete sequence of two new peptides from frog (Odorrana schmackeri) skin secretion. This involved reduction and alkylation with two different alkylating agents followed by high resolution tandem mass spectrometry. De novo sequencing was

  7. 125I-labeling and purification of peptide hormones and bovine serum albumin

    International Nuclear Information System (INIS)

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  9. 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

  10. Plasma levels of vasoactive regulatory peptides in patients receiving regular hemodialysis treatment.

    Science.gov (United States)

    Hegbrant, J; Thysell, H; Ekman, R

    1992-01-01

    The fasting plasma levels of 10 vasoactive regulatory peptides were measured by radioimmunoassay in 23 stable patients with chronic renal failure receiving regular hemodialysis treatment (RDT) and compared with those of healthy controls. The plasma concentrations of arginine vasopressin, atrial natriuretic peptide, beta-endorphin, methionine-enkephalin, motilin, neuropeptide Y, substance P, and vasoactive intestinal peptide were increased. The plasma level of calcitonin gene-related peptide was not statistically different from that of the controls. The plasma concentration of gamma 2-melanocyte-stimulating hormone was lowered in the RDT-patients. The arterial blood pressure correlated with the plasma levels of motilin and neuropeptide Y. We conclude that patients with chronic renal failure receiving RDT have increased concentrations of 8 out of 10 measured vasoactive regulatory peptides. The elevated levels of vasoactive peptides may contribute to the adaptation of the cardiovascular system to impaired renal function.

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Salmon calcitonin: conformational changes and stabilizer effects

    Directory of Open Access Journals (Sweden)

    Shan-Yang Lin

    2015-11-01

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

  13. Lmx1b controls peptide phenotypes in serotonergic and dopaminergic neurons

    Institute of Scientific and Technical Information of China (English)

    Rui Yan; Tianwen Huang; Zhiqin Xie; Guannan Xia; Hui Qian; Xiaolin Zhao; Leping Cheng

    2013-01-01

    Serotonin (5-HT) neurons synthesize a variety of peptides.How these peptides are controlled during development remains unclear.It has been reported that the co-localization of peptides and 5-HT varies by species.In contrast to the situations in the rostral 5-HT neurons of human and rat brains,several peptides do not coexist with 5-HT in the rostral 5-HT neurons of mouse brain.In this study,we found that the peptide substance P and peptide genes,including those encoding peptides thyrotropin-releasing hormone,enkephalin,and calcitonin gene-related peptide,were expressed in the caudal 5-HT neurons of mouse brain; these findings are in line with observations in rat and monkey 5-HT neurons.We also revealed that these peptides/peptide genes partially overlapped with the transcription factor Lmx1b that specifies the 5-HT cell fate.Furthermore,we found that the peptide cholecystokinin was expressed in developing dopaminergic neurons and greatly overlapped with Lmx1b that specifies the dopaminergic cell fate.By examining the phenotype of Lmx1b deletion mice,we found that Lmx1b was required for the expression of above peptides expressed in 5-HT or dopaminergic neurons.Together,our results indicate that Lmx1b,a key transcription factor for the specification of 5-HT and dopaminergic transmitter phenotypes during embryogenesis,determines some peptide phenotypes in these neurons as well.

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

    Directory of Open Access Journals (Sweden)

    Grabellus Florian

    2011-08-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tomoya Kon

    2012-03-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  18. Calcitonin

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    1991-08-01

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

  1. Transient expression of somatostatin messenger RNA and peptide in the hypoglossal nucleus of the neonatal rat.

    Science.gov (United States)

    Seroogy, K B; Bayliss, D A; Szymeczek, C L; Hökfelt, T; Millhorn, D E

    1991-06-21

    The postnatal developmental expression of somatostatin mRNA and peptide in the rat hypoglossal nucleus was analyzed using immunocytochemical and in situ hybridization techniques. Both the neuropeptide and its cognate mRNA were found to be transiently present within a subpopulation of hypoglossal motoneurons during the neonatal period. At the day of birth, a large population of perikarya situated in caudal, ventral regions of the hypoglossal nucleus expressed somatostatin. By postnatal day 7, the number of hypoglossal somata which expressed somatostatin had diminished considerably, and by 2 weeks postnatal, only few such cell bodies were found. By 3-4 weeks postnatal, somatostatin peptide- and mRNA-containing hypoglossal motoneurons were rarely observed, and in the adult, they were never detected, despite the use of colchicine. A double-labeling co-localization technique was used to demonstrate that somatostatin, when present perinatally, always coexisted with calcitonin gene-related peptide in hypoglossal motoneurons. The latter peptide, in contrast to somatostatin, was expressed in large numbers of somata throughout the entire hypoglossal nucleus and persisted within the motoneurons throughout development into adulthood. These results demonstrate that somatostatin is transiently expressed in motoneurons of the caudal, ventral tier of the hypoglossal nucleus in the neonatal rat. The developmental disappearance of somatostatin is most likely not due to cell death; hypoglossal somata continue to express calcitonin gene-related peptide, with which somatostatin coexisted perinatally, a high levels throughout development. Thus, it appears that the regulation of somatostatin expression in hypoglossal neurons occurs at the level of gene transcription or mRNA stability/degradation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1680035

  2. Regulatory peptides in the upper respiratory system and oral cavity of man. An immunocytochemical and radioimmunological study

    International Nuclear Information System (INIS)

    In the present study a dense network of peptide-immunoreactive nerve fibres in the upper respiratory system and the oral cavity of man was investigated. The occurrence, distribution and concentrations of regulatory peptide immunoreactivities in human nasal mucosa, soft palate, ventricular fold, vocal cord, epiglottis, subglottis, glandula submandibularis and glandula parotis were investigated using highly efficient immunocytochemical and radio-immunological methods. In the tissues investigated vasoactive intestinal polypeptide (VIP) and other derivatives from the VIP-precursor (peptide histidine methionine = PHM), prepro VIP (111-122)), neuropeptide tyrosine (NPY) and its C-flanking peptide (CPON), calcitonin gene-related peptide (CGRP), substance P, neurokinin A, bombesin-flanking peptide and somatostatin were detected. The regulatory peptides demonstrated also included the recently isolated peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP). Single endocrine-like cells were for the first time demonstrated within the respiratory epithelium and in the lamina propria of the nasal mucosa and soft palate and in groups within ducts. Ultrastructural immunelectronmicroscopy was performed using an ABC-pre-embedding method. In addition, semithin Epon resin sections were immunostained. The concentrations of VIP, NPY, CGRP, substance P and neurokinin A were measured using radioimmunological methods. The peptide immunoreactivities demonstrated in a dense network of neuronal structures and endocrine cells give indication for the presence of a complex regulatory system with potent physiological mechanisms in the upper respiratory system and allocated tissues of man

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

    DEFF Research Database (Denmark)

    Wallengren, Joanna; Edvinsson, Lars

    2014-01-01

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

  4. Introduction to Peptide Synthesis

    OpenAIRE

    Stawikowski, Maciej; Fields, Gregg B.

    2002-01-01

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

  5. Morning or evening administration of nasal calcitonin?

    DEFF Research Database (Denmark)

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

    1997-01-01

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

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

    Science.gov (United States)

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

    1976-07-01

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

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

    Institute of Scientific and Technical Information of China (English)

    于静涛; 林莉; 刘纯义

    2001-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    吴庆建; 闫承军; 宋大庆; 刘云海; 孙树印

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    杨屹; 李勇; 王常林; 袁正伟

    2005-01-01

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

  10. Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.

    Science.gov (United States)

    Suzuki, Yosuke; Itoh, Hiroki; Abe, Tomohide; Nishimura, Fumihiro; Sato, Yuhki; Takeyama, Masaharu

    2011-01-01

    Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels. PMID:21963510

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

    OpenAIRE

    Mitchell, Emma

    2006-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tanaka,Juntaro

    1989-06-01

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

  13. Interaction between Pirenzepine and Ninjinto, a Traditional Japanese Herbal Medicine, on the Plasma Gut-Regulated Peptide Levels in Humans

    Directory of Open Access Journals (Sweden)

    Yuhki Sato

    2013-01-01

    Full Text Available The Japanese herbal medicine (Kampo Ninjinto has been used for the treatment of gastroenteritis, esogastritis, gastric atony, gastrectasis, vomiting, and anorexia. The pharmacological effects of Ninjinto on the gastrointestine are due to changes in the levels of gut-regulated peptide, such as motilin, somatostatin, calcitonin gene-related peptide (CGRP, substance P, and vasoactive intestinal polypeptide (VIP. The release of these peptides is controlled by acetylcholine (ACh from the preganglionic fibers of the parasympathetic nerve. Thus, we examined the effects of the selective M1 muscarinic receptor antagonist pirenzepine on the elevation of Ninjinto-induced plasma the area under the plasma gut-regulated peptide concentration-time curve from 0 to 240 min ( in humans. Oral pretreatment with pirenzepine significantly reduced the Ninjinto-induced elevation of plasma motilin and substance P release (. Combined treatment with Ninjinto and pirenzepine significantly increased the release of plasma somatostatin ( compared with administration of Ninjinto alone or placebo. Ninjinto appeared to induce the release of substance P and motilin into plasma mainly through the activation of M1 muscarinic receptors, and pirenzepine may affect the pharmacologic action of Ninjinto by the elevation of plasma substance P, motilin, and somatostatin.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    1987-12-01

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

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

    Science.gov (United States)

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

    1989-01-01

    Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption. PMID:2576918

  17. [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.

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

    Science.gov (United States)

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

    2015-01-01

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

  19. The Treatment of Sudeck Syndrorn or Algodystrophie by Calcitonin

    OpenAIRE

    Breintenfelder, J.; Yucel, M

    2004-01-01

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

  20. 21 CFR 862.1140 - Calcitonin test system.

    Science.gov (United States)

    2010-04-01

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

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

    Science.gov (United States)

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

    1996-01-01

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

  2. Rabeprazole's influence on duodenal ulcer patients' serum levels of gastrointestinal peptide hormone and neurotransmitter

    Institute of Scientific and Technical Information of China (English)

    Xiao-Chun Zhong; Hong-Yan Duan; Wang-Qiong Xu

    2015-01-01

    Objective:To observe the effects of rabeprazole of duodenal ulcer, and its influence on the serum levels of gastrointestinal peptide hormone and neurotransmitter.Methods:180 patients with duodenal ulcer were randomly divided into control group and observation group, each group had 90 cases, patients in control group were given routine treatment, and those in observation group were treated with rabeprazole 20 mg/time, 2 times/d, treatment for 4 weeks based on routine treatment. Then gastroscopy and 14C- urea breath test were took before and after treatment for comparison of efficacy between the two groups, and the serum levels of gastrointestinal hormone such as gastrin (Gas), motilin (MTL), somatostatin (SS) and calcitonin gene related peptide (CGRP) and neurotransmitter such as 5- serotonin (5-HT), substance P (SP), nitric oxide (NO), vasoactive intestinal peptide (VIP) of two groups before and after treatment were detected and compared.Results:3, 5 weeks after treatment, the stomach integral of observation group was lower than that of the control group, stomach pain relief time was shorter than control group, Hp eradication rate was higher than control group, and the curative effect of observation group was significantly better than the control group. 3, 5 weeks after treatment, the serum levels of Gas, AM, MTL and 5-HT, SP, NO, VIP level of observation group were significantly lower than that of the control group, while the SS and CGRP were higher than the control group.Conclusion:Rabeprazole can effectively regulate the expression of gastrointestinal peptide hormone and neurotransmitter of patients with duodenal ulcer, shorten the recovery time and improve the curative effect.

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

    Science.gov (United States)

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

    2007-04-01

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

  4. Circulating parathyroid hormone and calcitonin in rats after spaceflight

    Science.gov (United States)

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

    1992-01-01

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

  5. Effect of botulinum toxin type A on the expression of substance P, calcitionin gene-related peptide,transforming growth factor beta-1 and alpha smooth muscle actin A in wound healing in rats%肉毒毒素A对大鼠皮肤及创面组织中SP、CGRP、TGF-β1和α-SMA的影响

    Institute of Scientific and Technical Information of China (English)

    王琳; 邰宁正; 范志宏

    2009-01-01

    Objective To investigate the effect of botulinum toxin type A on the expression of substance P(SP),calcitionin gene-related peptide(CGRP), transforming growth factor beta-1 (TGF-β1) and alpha smooth muscle actin A(α-SMA) in wound healing. Methods 60 rats were randomly divided into group C (control)、 group L (low-dose) and group H (high-dose), with 20 rats in each group. The wound-healing model was established by excision of four full-thickness skin(1 cm×1 cm, around the injection site) on the back of all SD rats on the 7th day after BTA injection. The wound size was measured and the expression of SP, CGRP, TGF-β1 and α-SMA in wound granulation tissue was assayed by immanohistocbemical staining and computerized image analysis before operation, and 3 days, 7 days and 14 days after operation. Results All the wounds healed 14 days after operation. The wound size in L and H group was not significantly different with that in C group on the 3rd day and 7th day after operation. The positive immuno-staining of SP, CGRP, TGF-β1 and α-SMA in group L and H was significantly weaker than those in C group. Meanwhile, the positive immuno-staining of all above substances in H group was weaker than those in L group significantly. Conclusions Botulinum toxin type A can decrease the expression of SP, CGRP, TGF-β1 and α-SMA in wound healing in a dose-dependent manner with no effect on the healing time.%目的 探讨肉毒毒素A对周围神经末梢释放的感觉神经肽P物质、降钙素基因相关肽及创面组织表达TGF-β1和α-平滑肌肌动蛋白的影响. 方法 60只SD大鼠随机分为空白对照组(C组)、低剂量组(L组)和高剂量组(H组),每组加只大鼠.肉毒毒素A预注射后7 d,在鼠背部建立以4个注射点为中心的创面模型,创面面积1 cm×1 cm.于术前及术后3、7、14 d,测量创面面积,免疫组织化学和Axioplan 2 Imaging图像分析软件检测多聚甲醛灌注后创面P物质、降钙素基因相关肽以及创

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

    International Nuclear Information System (INIS)

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  8. 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.

  9. EFFECTS OF CERTAIN VASOACTIVE PEPTIDES ON PATHOGENESIS OF VASCULAR RESTENOSIS

    Institute of Scientific and Technical Information of China (English)

    刘乃奎; 陈光慧; 王晓红; 姚兴海; 苏加林; 李田昌; 武旭东; 张勇刚; 汤健; 唐朝枢

    2003-01-01

    Objective.To investigate the effects of several vasoactive peptides on the development of arterial restenosis after balloon angioplasty. Methods. In rat aortic artery restenosis model produced by denudation of aortic endothelia,we observed changes of endothelin(ET),angiotensin II(AII),calcitonin gene-related peptide(CGRP)and adrenomedullin(Adm)in plasma and aorta with radioimmunoassay and expression of hypertension-related gene(HRG-1)with semi-quantitative RT-PCR,and studied the effects of these peptides on intimal hyperplasia,intima/media ratio and MAPK activities of aortic artery after angioplasty respectively. Furthermore,in cultured cells,we studied the effects of these peptides on vascular smooth muscle cell(VSMC) proliferation and expression of HRG-1 of VSMC from spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats with 3H-TdR incorporation and RT-PCR respectively. Results. After angioplasty,the levels of ET and AII in plasma and aorta significantly increased,accompanied with VSMC proliferation and neointima hyperplasia. On day 10 after angioplasty,the levels of ET in plasma and aorta increased by 69% and 124% respectively,compared with sham group(P<0.01);and the level of aortic AII increased by 80%(P< 0.01). Antiserum against ET or inhibitors of angiotensin converting enzyme(ACE)could significantly inhibit the proliferation of VSMC and neointima formation. Compared with the sham group,on day 3 after angioplasty,the CGRP levels in plasma and aorta increased by 64% and 89% respectively(P< 0.01)and the Adm levels in plasma and tissue increased by 129% and 102% respectively(P< 0.01). On day 10,intravenous administration of CGRP significantly inhibited the proliferation of VSMC and neointima forma-tion induced by balloon aortic injury(by 66% and 79% respectively,P< 0.01). In addition,ET and AII attenuated the expression of HRG-1 in aorta and stimulated mitogen-activated protein kinase(MAPK)activity,while CGRP and Adm potentiated the expression of HRG-1

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

    Institute of Scientific and Technical Information of China (English)

    王双侠; 魏雅冬; 戴明

    2011-01-01

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

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

    Science.gov (United States)

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

    2003-08-01

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

  12. Gene expression for peptides in neurons of the petrosal and nodose ganglia in rat.

    Science.gov (United States)

    Czyzyk-Krzeska, M F; Bayliss, D A; Seroogy, K B; Millhorn, D E

    1991-01-01

    In situ hybridization was used to determine whether genes for neuropeptides [substance P/neurokinin A (SP/NKA), calcitonin gene-related peptide (CGRP), somatostatin (SOM), neuropeptide tyrosine (NPY) and cholecystokinin (CCK)] are expressed in inferior ganglia of the vagus (nodose) and glossopharyngeal (petrosal) nerves. Synthetic oligodeoxyribonucleotides, complementary to the cognate, mRNAs were labeled with [32P] or [35S], and hybridized to 10 microns thick sections of unperfused tissue which were then processed for film and emulsion autoradiography. We found numerous, clustered neuronal perikarya throughout the nodose and petrosal ganglia that expressed preprotachykinin A (SP/NKA) and CGRP mRNAs to varying degrees. Neurons expressing preproSOM mRNA were less abundant and more scattered throughout both ganglia. Notably, we found mRNA for NPY in cells (usually 5-10 per section) in both ganglia. To our knowledge, this is first evidence for NPY in these sensory ganglia. In contrast to previous immunohistochemical findings, we found no evidence for expression of preproCCK in either the nodose or petrosal ganglia. The present findings demonstrate that cells of the nodose and petrosal ganglia express the genes for a number of neuropeptides that are presumably involved with transmission of visceral sensory afferent information to higher order neurons of the central nervous system. PMID:1708726

  13. Changes in plasma levels of vasoactive peptides during sequential bicarbonate hemodialysis.

    Science.gov (United States)

    Hegbrant, J; Thysell, H; Mårtensson, L; Ekman, R; Boberg, U

    1993-01-01

    The hemodynamic response to isolated ultrafiltration (IUF) is characterized by a vasoconstriction, while there is no significant change in peripheral vascular resistance during isovolemic bicarbonate hemodialysis (IVHD). The present investigation was designed to study the plasma levels of vasoactive regulatory peptides together with noradrenaline (NA) and plasma renin activity (PRA) in 11 patients during sequential hemodialysis (SQHD) - IUF for 60 min, followed by IVHD for 210 min. During IUF, the vasoconstrictors arginine vasopressin (AVP), gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY), NA and PRA increased. During IVHD, NPY and PRA remained unchanged on a higher level. A decrease in AVP below the baseline and in gamma 2-MSH and NA to the baseline levels occurred during IVHD. In the case of vasodilators, there were no changes in calcitonin gene-related peptide or motilin during SQHD. An increase in beta-endorphin (beta-END) occurred during IUF, followed by a decrease during IVHD. Substance P and vasoactive intestinal peptide were unchanged during IUF but decreased during IVHD. We conclude that SQHD is characterized by an increase in all the measured vasoconstrictors during IUF in response to loss of fluid, and by a decrease in some vasoconstrictors (AVP, gamma 2-MSH, NA) during IVHD. With the exception of beta-END, there were no changes or only minor ones in vasodilators during SQHD. There are changes in plasma levels of vasoactive substances during SQHD but the importance of these changes for the hemodynamic adaptation to ultrafiltration and dialysis needs to be studied further.

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

    Institute of Scientific and Technical Information of China (English)

    WANG Shi-xiang; LI Han

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ito Akitoshi

    2012-06-01

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

  16. Minimizing acylation of peptides in PLGA microspheres

    OpenAIRE

    Zhang, Ying; Schwendeman, Steven P.

    2012-01-01

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

  17. Experimental Cancer Cachexia Changes Neuron Numbers and Peptide Levels in the Intestine: Partial Protective Effects after Dietary Supplementation with L-Glutamine

    Science.gov (United States)

    Vicentini, Geraldo E.; Fracaro, Luciane; de Souza, Sara R. G.; Martins, Heber A.; Guarnier, Flávia A.; Zanoni, Jacqueline N.

    2016-01-01

    Gastrointestinal dysmotility frequently occurs in cancer cachexia and may result from damage to enteric innervation caused by oxidative stress, especially due to glutathione depletion. We assessed the effect of dietary supplementation with 20 g/kg l-glutamine (a glutathione precursor) on the intrinsic innervation of the enteric nervous system in healthy and Walker 256 tumor-bearing Wistar rats during the development of experimental cachexia (14 days), in comparison with non-supplemented rats, by using immunohistochemical methods and Western blotting. The total neural population and cholinergic subpopulation densities in the myenteric plexus, as well as the total population and VIPergic subpopulation in the submucosal plexus of the jejunum and ileum, were reduced in cachectic rats, resulting in adaptive morphometric alterations and an increase in vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) expression, suggesting a neuroplastic response. l-glutamine supplementation prevented decrease in myenteric neuronal density in the ileum, morphometric alterations in the neurons and nerve fibers (in both the plexuses of the jejunum and ileum), and the overexpression of VIP and CGRP. Cancer cachexia severely affected the intrinsic innervation of the jejunum and ileum to various degrees and this injury seems to be associated with adaptive neural plasticity. l-glutamine supplementation presented partial protective effects on the enteric innervation against cancer cachexia, possibly by attenuating oxidative stress. PMID:27635657

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

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    Caterina Morabito

    2015-05-01

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

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

    Science.gov (United States)

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

    1987-08-01

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

  20. Optimizing the radioimmunologic determination methods for cortisol and calcitonin

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    1978-05-01

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

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

    International Nuclear Information System (INIS)

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

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

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    Galit Fichman

    2014-08-01

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

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

    International Nuclear Information System (INIS)

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

  5. Cross-species comparison of genes related to nutrient sensing mechanisms expressed along the intestine.

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    Nikkie van der Wielen

    Full Text Available Intestinal chemosensory receptors and transporters are able to detect food-derived molecules and are involved in the modulation of gut hormone release. Gut hormones play an important role in the regulation of food intake and the control of gastrointestinal functioning. This mechanism is often referred to as "nutrient sensing". Knowledge of the distribution of chemosensors along the intestinal tract is important to gain insight in nutrient detection and sensing, both pivotal processes for the regulation of food intake. However, most knowledge is derived from rodents, whereas studies in man and pig are limited, and cross-species comparisons are lacking.To characterize and compare intestinal expression patterns of genes related to nutrient sensing in mice, pigs and humans.Mucosal biopsy samples taken at six locations in human intestine (n = 40 were analyzed by qPCR. Intestinal scrapings from 14 locations in pigs (n = 6 and from 10 locations in mice (n = 4 were analyzed by qPCR and microarray, respectively. The gene expression of glucagon, cholecystokinin, peptide YY, glucagon-like peptide-1 receptor, taste receptor T1R3, sodium/glucose cotransporter, peptide transporter-1, GPR120, taste receptor T1R1, GPR119 and GPR93 was investigated. Partial least squares (PLS modeling was used to compare the intestinal expression pattern between the three species.The studied genes were found to display specific expression patterns along the intestinal tract. PLS analysis showed a high similarity between human, pig and mouse in the expression of genes related to nutrient sensing in the distal ileum, and between human and pig in the colon. The gene expression pattern was most deviating between the species in the proximal intestine. Our results give new insights in interspecies similarities and provide new leads for translational research and models aiming to modulate food intake processes in man.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    1978-01-01

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

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

    Science.gov (United States)

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

    2012-08-01

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

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

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    Sekiguchi Miho

    2008-12-01

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

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

    OpenAIRE

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

    2012-01-01

    The aim of this work was to evaluate the association of low-level laser therapy (LLLT, 830 nm) and calcitonin in bone repair considering that bone healing remains a challenge to health professionals. Calcitonin has antiosteoclastic action and LLLT is a treatment that uses low-level lasers or light-emitting diodes to alter cellular function. Both are used to improve bone healing. Densitometry is a clinical noninvasive valuable tool used to evaluate bone mineral density (BMD). Sixty male rats w...

  13. Molecular functions of genes related to grain shape in rice

    OpenAIRE

    Zheng, Jia; Zhang, Yadong; Wang, Cailin

    2015-01-01

    Because grain shape is an important component of rice grain yield, the discovery of genes related to rice grain shape has attracted much attention of rice breeding programs. In recent years, some of these genes have been cloned and studied. They have been found not only regulate grain shape by changing the shape of the spikelet hull, but also regulate endosperm development through control of cell division using different molecular mechanisms. In this paper, we review the recent research on ge...

  14. Headache: Hope through Research

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren

    2005-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-09-28

    Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45μmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations. PMID:27480451

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

    Science.gov (United States)

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

    2013-07-01

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

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

    Science.gov (United States)

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

    1989-12-01

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

  1. 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.)

  2. The role of histamine in neurogenic inflammation

    OpenAIRE

    Rosa, A. C.; Fantozzi, R

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-05-17

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

  4. 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.

  5. Vasoactive peptide and obstruction sleep apnea syndrome%血管活性肽与阻塞性睡眠呼吸暂停综合征

    Institute of Scientific and Technical Information of China (English)

    刘维英

    2011-01-01

    , calcitonin gene related peptide are currently found the major vasoactive peptides, vasoconstrictive peptides and vasodilative peptides, imbalances might be OSAS patients disease of heart and head blood-vessel foundation, but its mechanism has not quite clear and controversial up to now, as involving ischemia, endocrine and neuromodulation abnormal, inflammation,oxidative stress and so on many kinds of the pathologic process, OSAS may exist complex pathogenic factors. This article sum up the research of the major vasoactivc peptide and OSAS in order to realize their relationship.

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

    International Nuclear Information System (INIS)

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

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

    OpenAIRE

    Poštić Srđan D.

    2013-01-01

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

  8. Genes related to high temperature tolerance during maize seed germination.

    Science.gov (United States)

    Dutra, S M F; Von Pinho, E V R; Santos, H O; Lima, A C; Von Pinho, R G; Carvalho, M L M

    2015-01-01

    The identification of genes related to heat tolerance is fundamental for the development of high-quality seeds that are tolerant to heat stress condition. The objective of this study was to evaluate maize lineages and the gene expression involved in high temperature tolerance during germination using physiological tests, proteomics, and transcriptome analysis. Seeds from six maize lineages (30, 44, 54, 63, 64, and 91) with different levels of tolerance to high temperatures were used. Lineages 54 and 91 were observed to be more tolerant to high temperature conditions. The highest expression of α-amylase was observed in maize seeds from lineages 30 and 91 that were subjected to controlled deterioration. The highest expression of α-amylase was observed in maize seeds from lineages 30 and 91 that were subjected to controlled deterioration; with the controlled deterioration, the highest level of gene expression did not occur in the most tolerant materials; the association of lower expression of genes involved in heat-resistant protein systems was observed in seeds from lineage 44, which were more susceptible to high temperatures, and the highest gene expression of LEA D-34, ZmAN13, and AOX-1 was observed in seeds from lineage 64 when submitted to controlled deterioration. PMID:26782452

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

    Science.gov (United States)

    Haddadi, Kaveh; Asadian, Leila; Isazade, Ahdie

    2016-01-01

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

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

    Science.gov (United States)

    Goebell, H; Hotz, J

    1976-03-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  13. Aerosolized Medications for Gene and Peptide Therapy.

    Science.gov (United States)

    Laube, Beth L

    2015-06-01

    Inhalation therapy has matured to include drugs that: (1) deliver nucleic acids that either lead to the restoration of a gene construct or protein coding sequence in a population of cells or suppress or disrupt production of an abnormal gene product (gene therapy); (2) deliver peptides that target lung diseases such as asthma, sarcoidosis, pulmonary hypertension, and cystic fibrosis; and (3) deliver peptides to treat diseases outside the lung whose target is the systemic circulation (systemic drug delivery). These newer applications for aerosol therapy are the focus of this paper, and I discuss the status of each and the challenges that remain to their successful development. Drugs that are highlighted include: small interfering ribonucleic acid to treat lung cancer and Mycobacterium tuberculosis; vectors carrying the normal alpha-1 antitrypsin gene to treat alpha-1 antitrypsin deficiency; vectors carrying the normal cystic fibrosis transmembrane conductance regulator gene to treat cystic fibrosis; vasoactive intestinal peptide to treat asthma, pulmonary hypertension, and sarcoidosis; glutathione to treat cystic fibrosis; granulocyte-macrophage colony-stimulating factor to treat pulmonary alveolar proteinosis; calcitonin for postmenopausal osteoporosis; and insulin to treat diabetes. The success of these new aerosol applications will depend on many factors, such as: (1) developing gene therapy formulations that are safe for acute and chronic administrations to the lung, (2) improving the delivery of the genetic material beyond the airway mucus barrier and cell membrane and transferring the material to the cell cytoplasm or the cell nucleus, (3) developing aerosol devices that efficiently deliver genetic material and peptides to their lung targets over a short period of time, (4) developing devices that increase aerosol delivery to the lungs of infants, (5) optimizing the bioavailability of systemically delivered peptides, and (6) developing peptide formulations for

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

    Science.gov (United States)

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

    2015-05-01

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

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

    International Nuclear Information System (INIS)

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

  16. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

    Werle, Martin; Takeuchi, Hirofumi

    2009-03-31

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

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

    Science.gov (United States)

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

    1980-01-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    1998-09-01

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

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

    Science.gov (United States)

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

    2007-10-01

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

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

    DEFF Research Database (Denmark)

    Hasselgren, Martin; Hegedüs, Laszlo; Godballe, Christian;

    2009-01-01

    BACKGROUND: Routine measurement of serum calcitonin to detect medullary thyroid carcinoma (MTC) continues to be fiercely debated, although less attention has been paid to the positive predictive value (PPV) of this method. METHODS: We collected data from 959 patients with nontoxic nodular goiter...... were classified correctly initially. The sensitivity of serum calcitonin for detection of MTC was 100%, the specificity was 95.3%, the positive predictive value was 15.4%, and the negative predictive value was 100%. CONCLUSION: Serum calcitonin has high sensitivity and specificity for detection of MTC....... The low PPV might lead to unnecessary thyroid surgery. Thus, the result of serum calcitonin measurement should always be interpreted in the context of other clinical variables. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009....

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

    Institute of Scientific and Technical Information of China (English)

    BAI; Zhi-yong

    2001-01-01

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

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

    International Nuclear Information System (INIS)

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

  6. Importance of a proper placement for your data point

    Institute of Scientific and Technical Information of China (English)

    Zong-Jie Cui

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2016-07-30

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

  10. In vitro and in vivo preclinical evaluation of a minisphere emulsion-based formulation (SmPill®) of salmon calcitonin.

    Science.gov (United States)

    Aguirre, Tanira A S; Rosa, Mónica; Coulter, Ivan S; Brayden, David J

    2015-11-15

    Salmon calcitonin (sCT, MW 3432Da) is a benchmark molecule for an oral peptide delivery system because it is degraded and has low intestinal epithelial permeability. Four dry emulsion minisphere prototypes (SmPill®) containing sCT were co-formulated with permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10) or coco-glucoside (CG), or with a pH acidifier, citric acid (CA). Minispheres protected sCT from thermal degradation and the released sCT retained high bioactivity, as determined by cyclic AMP generation in T47D cells. Pre-minisphere emulsions of PEs combined with sCT increased absolute bioavailability (F) compared to native sCT following rat intra-jejunal (i.j.) and intra-colonic (i.c.) loop instillations, an effect that was more pronounced in colon. Minispheres corresponding to ~2000I.U. (~390μg) sCT/kg were instilled by i.j. or i.c. instillations and hypocalcaemia resulted from all prototypes. The absolute F (i.j.) of sCT was 11.0, 4.8, and 1.4% for minispheres containing NaTDC (10μmol/kg), CG (12μmol/kg) or CA (32μmol/kg) respectively. For i.c. instillations, the largest absolute F (22% in each case) was achieved for minispheres containing either C10 (284μmol/kg) or CG (12μmol/kg), whilst the absolute F was 8.2% for minispheres loaded with CA (32μmol/kg). In terms of relative F, the best data were obtained for minispheres containing NaTDC (i.j.), a 4-fold increase over sCT solution, and also for either C10 or CG (i.c.), where there was a 3-fold increase over sCT solution. Histology of instilled intestinal loops indicated that neither the minispheres nor components thereof caused major perturbation. In conclusion, selected SmPill® minisphere formulations may have the potential to be used as oral peptide delivery systems when delivered to jejunum or colon. PMID:26349051

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

    Science.gov (United States)

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

    2011-10-01

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

  12. Amplification of a Gene Related to Mammalian mdr Genes in Drug-Resistant Plasmodium falciparum

    Science.gov (United States)

    Wilson, Craig M.; Serrano, Adelfa E.; Wasley, Annemarie; Bogenschutz, Michael P.; Shankar, Anuraj H.; Wirth, Dyann F.

    1989-06-01

    The malaria parasite Plasmodium falciparum contains at least two genes related to the mammalian multiple drug resistance genes, and at least one of the P. falciparum genes is expressed at a higher level and is present in higher copy number in a strain that is resistant to multiple drugs than in a strain that is sensitive to the drugs.

  13. Antimicrobial peptides.

    Science.gov (United States)

    Zhang, Ling-Juan; Gallo, Richard L

    2016-01-11

    Antimicrobial peptides and proteins (AMPs) are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multicellular organisms. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, viruses and even cancer cells. Insects and plants primarily deploy AMPs as an antibiotic to protect against potential pathogenic microbes, but microbes also produce AMPs to defend their environmental niche. In higher eukaryotic organisms, AMPs can also be referred to as 'host defense peptides', emphasizing their additional immunomodulatory activities. These activities are diverse, specific to the type of AMP, and include a variety of cytokine and growth factor-like effects that are relevant to normal immune homeostasis. In some instances, the inappropriate expression of AMPs can also induce autoimmune diseases, thus further highlighting the importance of understanding these molecules and their complex activities. This Primer will provide an update of our current understanding of AMPs. PMID:26766224

  14. Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2013-11-01

    Full Text Available The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs, a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    R. Coifman

    1997-06-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2007-03-01

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

  20. 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.

  1. Identification of Candidate Genes related to Bovine Marbling using Protein-Protein Interaction Networks

    OpenAIRE

    Lim, Dajeong; Kim, Nam-Kuk; Park, Hye-Sun; Lee, Seung-Hwan; Cho, Yong-Min; Oh, Sung Jong; Kim, Tae-Hun; Kim, Heebal

    2011-01-01

    Complex traits are determined by the combined effects of many loci and are affected by gene networks or biological pathways. Systems biology approaches have an important role in the identification of candidate genes related to complex diseases or traits at the system level. The present study systemically analyzed genes associated with bovine marbling score and identified their relationships. The candidate nodes were obtained using MedScan text-mining tools and linked by protein-protein intera...

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

    OpenAIRE

    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 relationship...

  3. Identification of genes related to germination in aged maize seed by screening natural variability

    OpenAIRE

    Revilla Temiño, Pedro; Butrón Gómez, Ana María; Rodríguez Graña, Víctor Manuel; Malvar Pintos, Rosa Ana; Ordás Pérez, Amando

    2009-01-01

    Ageing reduces vigour and viability in maize inbred lines due to non-heritable degenerative changes. Besides non-heritable genetic changes due to chromosome aberrations and damage in the DNA sequence, heritable changes during maize conservation have been reported. Genetic variability among aged seeds of inbred lines could be used for association studies with seed germination. The objective of this study was to identify genes related to germination in aged seeds. The sweet corn inbred line P39...

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

    Science.gov (United States)

    Swarup, K; Tewari, N P

    1980-01-01

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

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

    Science.gov (United States)

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

    1984-05-01

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

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

    Science.gov (United States)

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

    2003-11-01

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

  7. Human peptide transporters

    DEFF Research Database (Denmark)

    Nielsen, Carsten Uhd; Brodin, Birger; Jørgensen, Flemming Steen;

    2002-01-01

    Peptide transporters are epithelial solute carriers. Their functional role has been characterised in the small intestine and proximal tubules, where they are involved in absorption of dietary peptides and peptide reabsorption, respectively. Currently, two peptide transporters, PepT1 and PepT2...

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

    NARCIS (Netherlands)

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

    1993-01-01

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

  9. Improved glucose control and reduced body weight in rodents with dual mechanism of action peptide hybrids.

    Science.gov (United States)

    Trevaskis, James L; Mack, Christine M; Sun, Chengzao; Soares, Christopher J; D'Souza, Lawrence J; Levy, Odile E; Lewis, Diane Y; Jodka, Carolyn M; Tatarkiewicz, Krystyna; Gedulin, Bronislava; Gupta, Swati; Wittmer, Carrie; Hanley, Michael; Forood, Bruce; Parkes, David G; Ghosh, Soumitra S

    2013-01-01

    Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such as diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted the therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared to monotherapy. Here, we extend this hypothesis by linking a known anti-diabetic peptide with an anti-obesity peptide into a novel peptide hybrid, which we termed a phybrid. We report on the synthesis and biological activity of two such phybrids (AC164204 and AC164209), comprised of a glucagon-like peptide-1 receptor (GLP1-R) agonist, and exenatide analog, AC3082, covalently linked to a second generation amylin analog, davalintide. Both molecules acted as full agonists at their cognate receptors in vitro, albeit with reduced potency at the calcitonin receptor indicating slightly perturbed amylin agonism. In obese diabetic Lep(ob)/Lep (ob) mice sustained infusion of AC164204 and AC164209 reduced glucose and glycated haemoglobin (HbA1c) equivalently but induced greater weight loss relative to exenatide administration alone. Weight loss was similar to that induced by combined administration of exenatide and davalintide. In diet-induced obese rats, both phybrids dose-dependently reduced food intake and body weight to a greater extent than exenatide or davalintide alone, and equal to co-infusion of exenatide and davalintide. Phybrid-mediated and exenatide + davalintide-mediated weight loss was associated with reduced adiposity and preservation of lean mass. These data are the first to provide in vivo proof-of-concept for multi-pathway targeting in metabolic disease via a peptide hybrid, demonstrating that this approach is as effective as co-administration of individual peptides. PMID:24167604

  10. Improved glucose control and reduced body weight in rodents with dual mechanism of action peptide hybrids.

    Directory of Open Access Journals (Sweden)

    James L Trevaskis

    Full Text Available Combination therapy is being increasingly used as a treatment paradigm for metabolic diseases such as diabetes and obesity. In the peptide therapeutics realm, recent work has highlighted the therapeutic potential of chimeric peptides that act on two distinct receptors, thereby harnessing parallel complementary mechanisms to induce additive or synergistic benefit compared to monotherapy. Here, we extend this hypothesis by linking a known anti-diabetic peptide with an anti-obesity peptide into a novel peptide hybrid, which we termed a phybrid. We report on the synthesis and biological activity of two such phybrids (AC164204 and AC164209, comprised of a glucagon-like peptide-1 receptor (GLP1-R agonist, and exenatide analog, AC3082, covalently linked to a second generation amylin analog, davalintide. Both molecules acted as full agonists at their cognate receptors in vitro, albeit with reduced potency at the calcitonin receptor indicating slightly perturbed amylin agonism. In obese diabetic Lep(ob/Lep (ob mice sustained infusion of AC164204 and AC164209 reduced glucose and glycated haemoglobin (HbA1c equivalently but induced greater weight loss relative to exenatide administration alone. Weight loss was similar to that induced by combined administration of exenatide and davalintide. In diet-induced obese rats, both phybrids dose-dependently reduced food intake and body weight to a greater extent than exenatide or davalintide alone, and equal to co-infusion of exenatide and davalintide. Phybrid-mediated and exenatide + davalintide-mediated weight loss was associated with reduced adiposity and preservation of lean mass. These data are the first to provide in vivo proof-of-concept for multi-pathway targeting in metabolic disease via a peptide hybrid, demonstrating that this approach is as effective as co-administration of individual peptides.

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

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

    OpenAIRE

    Peatfield, Richard; Villalón, Carlos M

    2013-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer

    2011-01-01

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

  20. Possible site of action of CGRP antagonists in migraine

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Olesen, Jes

    2011-01-01

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

  1. A second trigeminal CGRP receptor

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    LIN; Xi-ran

    2001-01-01

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

  3. A pathophysiological view of primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2000-01-01

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

  4. Pathophysiology of primary headaches

    DEFF Research Database (Denmark)

    Edvinsson, L

    2001-01-01

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

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

    OpenAIRE

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

    1997-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present...... study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ...... was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes....

  12. A gene and protein expression study on four porcine genes related to intramuscular fat deposition.

    Science.gov (United States)

    Zappaterra, Martina; Deserti, Marzia; Mazza, Roberta; Braglia, Silvia; Zambonelli, Paolo; Davoli, Roberta

    2016-11-01

    Intramuscular fat (IMF) content has a prominent role in meat quality, affecting sensory attributes such as flavour and texture. In the present research, we studied in samples of porcine Semimembranosus muscle four genes related to lipid metabolism and whose gene expressions have been associated to IMF deposition: FASN, SCD, LIPE and LPL. We analysed both mRNA and protein expressions in two groups of Italian Large White pigs divergent for Semimembranosus IMF deposition, with the aim of comparing the levels of four genes and enzymes between the two groups and identifying possible coexpression links. The obtained results suggest a prominent role of LIPE enzyme in IMF hydrolysis, as the samples with low IMF deposition show a significantly higher amount of this lipase. Finally, a poorly known correlation was found between LIPE and FASN enzymes only in female individuals. These results provide new information for the understanding of IMF deposition. PMID:27236338

  13. PeptideAtlas

    Data.gov (United States)

    U.S. Department of Health & Human Services — PeptideAtlas is a multi-organism, publicly accessible compendium of peptides identified in a large set of tandem mass spectrometry proteomics experiments. Mass...

  14. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  15. Antimicrobial Peptides in 2014

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2015-03-01

    Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

  16. Peptide Nucleic Acid Synthons

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  17. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2003-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  18. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  19. Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    2002-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  20. Peptide-Carrier Conjugation

    DEFF Research Database (Denmark)

    Hansen, Paul Robert

    2015-01-01

    To produce antibodies against synthetic peptides it is necessary to couple them to a protein carrier. This chapter provides a nonspecialist overview of peptide-carrier conjugation. Furthermore, a protocol for coupling cysteine-containing peptides to bovine serum albumin is outlined....

  1. Peptides: Basic determinants of reproductive functions.

    Science.gov (United States)

    Celik, Onder; Aydin, Suleyman; Celik, Nilufer; Yilmaz, Musa

    2015-10-01

    Mammalian reproduction is a costly process in terms of energy consumption. The critical information regarding metabolic status is signaled to the hypothalamus mainly through peripheral peptides from the adipose tissue and gastrointestinal tract. Changes in energy stores produce fluctuations in leptin, insulin, ghrelin and glucose signals that feedback mainly to the hypothalamus to regulate metabolism and fertility. In near future, possible effects of the nutritional status on GnRH regulation can be evaluated by measuring serum or tissue levels of leptin and ghrelin in patiens suffering from infertility. The fact that leptin and ghrelin are antagonistic in their effects on GnRH neurons, their respective agonistic and antagonistic roles make them ideal candidates to use instead of GnRH agonist and antagonist. Similarly, kisspeptin expressing neurons are likely to mediate the well-established link between energy balance and reproductive functions. Exogenous kisspeptin can be used for physiological ovarian hyperstimulation for in-vitro fertilization. Moreover, kisspeptin antagonist therapy can be used for the treatment of postmenapousal women, precocious puberty, PCOS, endometriosis and uterine fibroids. In this review, we will analyze the central mechanisms involved in the integration of metabolic information and their contribution to the control of the reproductive function. Particular attention will be paid to summarize the participation of leptin, kisspeptin, ghrelin, NPY, orexin, urocortin, VIP, insulin, galanin, galanin like peptide, oxytocin, agouti gene-related peptide, and POMC neurons in this process and their possible interactions to contribute to the metabolic control of reproduction. PMID:26074346

  2. Expression of genes related to the regulation of muscle protein turnover in Angus and Nellore bulls.

    Science.gov (United States)

    Busato, K C; Gomes, R A; Ladeira, M M; Duarte, M S; Freitas, N C; Rodrigues, A C; Chalfun-Junior, A; Paiva, L V; Chizzotti, M L

    2016-04-01

    We aimed to evaluate the expression of genes related to the regulation of muscle protein turnover in the longissimus dorsi (LD) muscle of Angus and Nellore bulls and to estimate the within-breed correlations of gene expression and performance traits. Thirteen genes related to the IGF-1 and myostatin pathways were studied. Thirteen animals, with an initial average BW of 381.2 ± 11.8 kg, from each breed were used in a completely randomized 2 × 2 factorial design (2 breeds and 2 feeding levels). The diet consisted of corn silage and a corn-soybean meal concentrate in a roughage-to-concentrate ratio of 30:70. Cattle were fed ad libitum (with 9 animals from each breed) or feed restricted (a 55% restriction of total DMI of ad libitum-fed animals, calculated as percentage of metabolic BW, with 4 animals of each breed). The experimental period lasted for 82 d and it was preceded by a 28-d adaptation period. The performance traits evaluated were slaughter body weight, total ADG (from d 1 to 82 of the trial), initial ADG (from d 1 to 41 of the trial), final ADG (from d 42 to 82 of the trial), total DMI (from d 1 to 82 of the trial), initial DMI (from d 1 to 41 of the trial), final DMI (from d 42 to 82 of the trial), HCW, LD weight (LDW), and rib eye area (REA). After slaughter, samples were taken from the LD muscle between the 12th and 13th ribs for gene expression analysis by quantitative reverse transcription PCR. There was no difference ( > 0.05) in the expression of any of the genes studied between ad libitum-fed Angus and ad libitum-fed Nellore, whereas feed restriction increased the expression of (; < 0.001), (; = 0.05), and (; = 0.04) and decreased the expression of ( < 0.01). The REA was negatively correlated to (; = 0.01), (; = 0.02), and ( = 0.05). The HCW was negatively correlated to ( = 0.01) and ( = 0.01) and tended to be negatively correlated to ( = 0.07), whereas the LDW tended to be negatively correlated to ( = 0.08). The genes , , and seem to be important

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-12-01

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

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

    Science.gov (United States)

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

    1987-01-01

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

  6. Differentially expressed genes related with injury of human intestinal epithelium cell by γ-ray

    International Nuclear Information System (INIS)

    In order to isolate differentially expressed genes of intestinal epithelium cell related with γ radiation, by using HIEC cell line in vitro culture as research target, the cell line was irradiated by 8 Gy of γ ray and was continued to culture for 24 h as radiation group, the cell line without γ radiation was as control group. The authors isolated the differentially expressed genes between radiation group and control group by mRNA differential display. The authors obtained 101 fragments of differentially expressed genes, 31 of which were new expressed genes from radiation group, 29 of which were over expressed genes which was higher expressed in radiation group than in control group, 41 of which were no expression in radiation group and expression in control group, 31 of which were from the group of D-T11G as anchored primer, 59 of which were from the group of D-T11A as anchored primer, 32 of which were from the group of D-T11C as anchored primer. In summary, the authors obtained 101 fragments of differentially expressed genes related with γ radiation, 31 among them may be closely correlated with radiation damage to intestinal

  7. Identification of Candidate Genes related to Bovine Marbling using Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Dajeong Lim, Nam-Kuk Kim, Hye-Sun Park, Seung-Hwan Lee, Yong-Min Cho, Sung Jong Oh, Tae-Hun Kim, Heebal Kim

    2011-01-01

    Full Text Available Complex traits are determined by the combined effects of many loci and are affected by gene networks or biological pathways. Systems biology approaches have an important role in the identification of candidate genes related to complex diseases or traits at the system level. The present study systemically analyzed genes associated with bovine marbling score and identified their relationships. The candidate nodes were obtained using MedScan text-mining tools and linked by protein-protein interaction (PPI from the Human Protein Reference Database (HPRD. To determine key node of marbling, the degree and betweenness centrality (BC were used. The hub nodes and biological pathways of our network are consistent with the previous reports about marbling traits, and also suggest unknown candidate genes associated with intramuscular fat. Five nodes were identified as hub genes, which was consistent with the network analysis using quantitative reverse-transcription PCR (qRT-PCR. Key nodes of the PPI network have positive roles (PPARγ, C/EBPα, and RUNX1T1 and negative roles (RXRA, CAMK2A in the development of intramuscular fat by several adipogenesis-related pathways. This study provides genetic information for identifying candidate genes for the marbling trait in bovine.

  8. 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

  9. 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.

  10. 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

  11. 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

    2016-01-01

    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. PMID:27511178

  12. Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

    KAUST Repository

    Yan, Xing-Cheng

    2012-10-02

    The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

  13. Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

    Directory of Open Access Journals (Sweden)

    Xing-Cheng Yan

    Full Text Available The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in

  14. Transcriptomic analysis of neuropeptides and peptide hormones in the barnacle Balanus amphitrite: evidence of roles in larval settlement.

    Science.gov (United States)

    Yan, Xing-Cheng; Chen, Zhang-Fan; Sun, Jin; Matsumura, Kiyotaka; Wu, Rudolf S S; Qian, Pei-Yuan

    2012-01-01

    The barnacle Balanus amphitrite is a globally distributed marine crustacean and has been used as a model species for intertidal ecology and biofouling studies. Its life cycle consists of seven planktonic larval stages followed by a sessile juvenile/adult stage. The transitional processes between larval stages and juveniles are crucial for barnacle development and recruitment. Although some studies have been conducted on the neuroanatomy and neuroactive substances of the barnacle, a comprehensive understanding of neuropeptides and peptide hormones remains lacking. To better characterize barnacle neuropeptidome and its potential roles in larval settlement, an in silico identification of putative transcripts encoding neuropeptides/peptide hormones was performed, based on transcriptome of the barnacle B. amphitrite that has been recently sequenced. Potential cleavage sites andstructure of mature peptides were predicted through homology search of known arthropod peptides. In total, 16 neuropeptide families/subfamilies were predicted from the barnacle transcriptome, and 14 of them were confirmed as genuine neuropeptides by Rapid Amplification of cDNA Ends. Analysis of peptide precursor structures and mature sequences showed that some neuropeptides of B. amphitrite are novel isoforms and shared similar characteristics with their homologs from insects. The expression profiling of predicted neuropeptide genes revealed that pigment dispersing hormone, SIFamide, calcitonin, and B-type allatostatin had the highest expression level in cypris stage, while tachykinin-related peptide was down regulated in both cyprids and juveniles. Furthermore, an inhibitor of proprotein convertase related to peptide maturation effectively delayed larval metamorphosis. Combination of real-time PCR results and bioassay indicated that certain neuropeptides may play an important role in cypris settlement. Overall, new insight into neuropeptides/peptide hormones characterized in this study shall

  15. 6-Gingerol Protects against Nutritional Steatohepatitis by Regulating Key Genes Related to Inflammation and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Thing-Fong Tzeng

    2015-02-01

    Full Text Available Non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis (NASH, appears to be increasingly common worldwide. The aim of the study was to investigate the effects of 6-gingerol ((S-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl-3-decanone, a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of NASH. In HepG2 cells, 6-gingerol (100 μmol/L treatment inhibited free fatty acids mixture (0.33 mmol/L palmitate and 0.66 mmol/L oleate-induced triglyceride and inflammatory marker accumulations. Male C57BL/6 mice were fed with a methionine and choline-deficient (MCD diet to induce steatohepatitis. After four weeks of MCD diet feeding, the mice were dosed orally with 6-gingerol (25, 50 or 100 mg/kg/day once daily for another four weeks. 6-Gingerol (100 mg/kg/day attenuated liver steatosis and necro-inflammation in MCD diet-fed mice. The expressions of inflammatory cytokine genes, including those for monocyte chemoattractant protein-1, tumor necrosis factor-α, and interleukin-6, and nuclear transcription factor (NF-κB, which were increased in the livers of MCD diet-fed mice, were attenuated by 6-gingerol. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with induction of peroxisome proliferator-activated receptor α. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to lipid metabolism and inflammation.

  16. Transcriptional and functional studies of Acidithiobacillus ferrooxidans genes related to survival in the presence of copper.

    Science.gov (United States)

    Navarro, Claudio A; Orellana, Luis H; Mauriaca, Cecilia; Jerez, Carlos A

    2009-10-01

    The acidophilic Acidithiobacillus ferrooxidans can resist exceptionally high copper (Cu) concentrations. This property is important for its use in biomining processes, where Cu and other metal levels range usually between 15 and 100 mM. To learn about the mechanisms that allow A. ferrooxidans cells to survive in this environment, a bioinformatic search of its genome showed the presence of at least 10 genes that are possibly related to Cu homeostasis. Among them are three genes coding for putative ATPases related to the transport of Cu (A. ferrooxidans copA1 [copA1(Af)], copA2(Af), and copB(Af)), three genes related to a system of the resistance nodulation cell division family involved in the extraction of Cu from the cell (cusA(Af), cusB(Af), and cusC(Af)), and two genes coding for periplasmic chaperones for this metal (cusF(Af) and copC(Af)). The expression of most of these open reading frames was studied by real-time reverse transcriptase PCR using A. ferrooxidans cells adapted for growth in the presence of high concentrations of Cu. The putative A. ferrooxidans Cu resistance determinants were found to be upregulated when this bacterium was exposed to Cu in the range of 5 to 25 mM. These A. ferrooxidans genes conferred to Escherichia coli a greater Cu resistance than wild-type cells, supporting their functionality. The results reported here and previously published data strongly suggest that the high resistance of the extremophilic A. ferrooxidans to Cu may be due to part or all of the following key elements: (i) a wide repertoire of Cu resistance determinants, (ii) the duplication of some of these Cu resistance determinants, (iii) the existence of novel Cu chaperones, and (iv) a polyP-based Cu resistance system.

  17. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

    Directory of Open Access Journals (Sweden)

    Bert van der Zwaag

    Full Text Available The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD, and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.

  18. Plant signalling peptides

    OpenAIRE

    Wiśniewska, Justyna; Trejgell, Alina; Tretyn, Andrzej

    2003-01-01

    Biochemical and genetic studies have identified peptides that play crucial roles in plant growth and development, including defence mechanisms in response to wounding by pests, the control of cell division and expansion, and pollen self-incompatibility. The first two signalling peptides to be described in plants were tomato systemin and phytosulfokine (PSK). There is also biochemical evidence that natriuretic peptide-like molecules, immunologically-relatedt o those found ...

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

    Institute of Scientific and Technical Information of China (English)

    Xiaoli Xu; Qin Li; Lv Zhou; Liqiang Ru

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marco Diociaiuti

    2011-12-01

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

  1. Polycyclic peptide therapeutics.

    Science.gov (United States)

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia...

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

    Institute of Scientific and Technical Information of China (English)

    Li Yizhao; Sun Lin; Zhang Dongjun

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    K.R. Oliver

    2001-01-01

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

  5. Intrahepatic expression of genes related to metabotropic receptors in chronic hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andrzej Cie(s)la,; Maciej Ku(s)mider,; Agata Faron-Górecka; Marta Dziedzicka-Wasylewska; Monika Bociaga-Jasik; Danuta Owczarek; Irena Cie(c)ko-Michalska

    2012-01-01

    AIM:To screen for genes related to metabotropic receptors that might be involved in the development of chronic hepatitis.METHODS:Assessment of 20 genes associated with metabotropic receptors was performed in liver specimens obtained by punch biopsy from 12 patients with autoimmune and chronic hepatitis type B and C.For this purpose,a microarray with low integrity grade and with oligonucleotide DNA probes complementary to target transcripts was used.Evaluation of gene expression was performed in relation to transcript level,correlation between samples and grouping of clinical parameters used in chronic hepatitis assessment.Clinical markers of chronic hepatitis included alanine and aspartate aminotransferase,γ-glutamyltranspeptidase,alkaline phosphatase and cholinesterase activity,levels of iron ions,total cholesterol,triglycerides,albumin,glucose,hemoglobin,platelets,histological analysis of inflammatory and necrotic status,fibrosis according to METAVIR score,steatosis,as well as anthropometric body mass index,waist/hip index,percentage of adipose tissue and liver size in ultrasound examination.Gender,age,concomitant diseases and drugs were also taken into account.Validation of oligonucleotide microarray gene expression results was done with the use of quantitative real-time polymerase chain reaction (qRT-PCR).RESULTS:The highest (0.002 < P < 0.046) expression among genes encoding main components of metabotropic receptor pathways,such as the a subunit of G-coupled protein,phosphoinositol-dependent protein kinase or arrestin was comparable to that of angiotensinogen synthesized in the liver.Carcinogenesis suppressor genes,such as chemokine ligand 4,transcription factor early growth response protein 1 and lysophosphatidic acid receptor,were characterized by the lowest expression (0.002 < P < 0.046),while the factor potentially triggering hepatic cancer,transcription factor JUN-B,had a 20-fold higher expression.The correlation between expression of genes of

  6. Understanding migraine: Potential role of neurogenic inflammation

    OpenAIRE

    Rakesh Malhotra

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Edvinsson, L

    2001-01-01

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

  8. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  9. Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

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

    Institute of Scientific and Technical Information of China (English)

    苏娜; 吴逢波; 徐珽

    2013-01-01

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

  11. PNA Peptide chimerae

    DEFF Research Database (Denmark)

    Koch, T.; Næsby, M.; Wittung, P.;

    1995-01-01

    Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields....

  12. Tumor penetrating peptides

    Directory of Open Access Journals (Sweden)

    Tambet eTeesalu

    2013-08-01

    Full Text Available Tumor-homing peptides can be used to deliver drugs into tumors. Phage library screening in live mice has recently identified homing peptides that specifically recognize the endothelium of tumor vessels, extravasate, and penetrate deep into the extravascular tumor tissue. The prototypic peptide of this class, iRGD (CRGDKGPDC, contains the integrin-binding RGD motif. RGD mediates tumor homing through binding to αv integrins, which are selectively expressed on various cells in tumors, including tumor endothelial cells. The tumor-penetrating properties of iRGD are mediated by a second sequence motif, R/KXXR/K. This C-end Rule (or CendR motif is active only when the second basic residue is exposed at the C-terminus of the peptide. Proteolytic processing of iRGD in tumors activates the cryptic CendR motif, which then binds to neuropilin-1 activating an endocytic bulk transport pathway through tumor tissue. Phage screening has also yielded tumor-penetrating peptides that function like iRGD in activating the CendR pathway, but bind to a different primary receptor. Moreover, novel tumor-homing peptides can be constructed from tumor-homing motifs, CendR elements and protease cleavage sites. Pathologies other than tumors can be targeted with tissue-penetrating peptides, and the primary receptor can also be a vascular zip code of a normal tissue. The CendR technology provides a solution to a major problem in tumor therapy, poor penetration of drugs into tumors. The tumor-penetrating peptides are capable of taking a payload deep into tumor tissue in mice, and they also penetrate into human tumors ex vivo. Targeting with these peptides specifically increases the accumulation in tumors of a variety of drugs and contrast agents, such as doxorubicin, antibodies and nanoparticle-based compounds. Remarkably the drug to be targeted does not have to be coupled to the peptide; the bulk transport system activated by the peptide sweeps along any compound that is

  13. 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

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

    Science.gov (United States)

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

    2016-02-29

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

  15. Antimicrobial Peptides from Plants

    Science.gov (United States)

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  16. Antimicrobial Peptides from Plants

    Directory of Open Access Journals (Sweden)

    James P. Tam

    2015-11-01

    Full Text Available Plant antimicrobial peptides (AMPs have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic, lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms.

  17. Electron transfer in peptides.

    Science.gov (United States)

    Shah, Afzal; Adhikari, Bimalendu; Martic, Sanela; Munir, Azeema; Shahzad, Suniya; Ahmad, Khurshid; Kraatz, Heinz-Bernhard

    2015-02-21

    In this review, we discuss the factors that influence electron transfer in peptides. We summarize experimental results from solution and surface studies and highlight the ongoing debate on the mechanistic aspects of this fundamental reaction. Here, we provide a balanced approach that remains unbiased and does not favor one mechanistic view over another. Support for a putative hopping mechanism in which an electron transfers in a stepwise manner is contrasted with experimental results that support electron tunneling or even some form of ballistic transfer or a pathway transfer for an electron between donor and acceptor sites. In some cases, experimental evidence suggests that a change in the electron transfer mechanism occurs as a result of donor-acceptor separation. However, this common understanding of the switch between tunneling and hopping as a function of chain length is not sufficient for explaining electron transfer in peptides. Apart from chain length, several other factors such as the extent of the secondary structure, backbone conformation, dipole orientation, the presence of special amino acids, hydrogen bonding, and the dynamic properties of a peptide also influence the rate and mode of electron transfer in peptides. Electron transfer plays a key role in physical, chemical and biological systems, so its control is a fundamental task in bioelectrochemical systems, the design of peptide based sensors and molecular junctions. Therefore, this topic is at the heart of a number of biological and technological processes and thus remains of vital interest.

  18. Electromembrane extraction of peptides.

    Science.gov (United States)

    Balchen, Marte; Reubsaet, Léon; Pedersen-Bjergaard, Stig

    2008-06-20

    Rapid extraction of eight different peptides using electromembrane extraction (EME) was demonstrated for the first time. During an extraction time of 5 min, the model peptides migrated from a 500 microL aqueous acidic sample solution, through a thin supported liquid membrane (SLM) of an organic liquid sustained in the pores in the wall of a porous hollow fiber, and into a 25 microL aqueous acidic acceptor solution present inside the lumen of the hollow fiber. The driving force of the extraction was a 50 V potential sustained across the SLM, with the positive electrode in the sample and the negative electrode in the acceptor solution. The nature and the composition of the SLM were highly important for the EME process, and a mixture of 1-octanol and 15% di(2-ethylhexyl) phosphate was found to work properly. Using 1mM HCl as background electrolyte in the sample and 100 mM HCl in the acceptor solution, and agitation at 1050 rpm, enrichment up to 11 times was achieved. Recoveries were found to be dependent on the structure of the peptide, indicating that the polarity and the number of ionized groups were important parameters affecting the extraction efficiency. The experimental findings suggested that electromembrane extraction of peptides is possible and may be a valuable tool for future extraction of peptides. PMID:18479691

  19. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity......Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... and hence adjuvants are included to enhance and direct the immune response. Although the vaccine has been tested in ART naïve individuals, we recommend future testing of the vaccine during (early started) ART that improves immune function and to select individuals likely to benefit. Peptides representing...

  20. Synthetic antibiofilm peptides.

    Science.gov (United States)

    de la Fuente-Núñez, César; Cardoso, Marlon Henrique; de Souza Cândido, Elizabete; Franco, Octavio Luiz; Hancock, Robert E W

    2016-05-01

    Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. PMID:26724202

  1. Biomimetic peptide nanosensors.

    Science.gov (United States)

    Cui, Yue; Kim, Sang N; Naik, Rajesh R; McAlpine, Michael C

    2012-05-15

    The development of a miniaturized sensing platform tailored for sensitive and selective detection of a variety of biochemical analytes could offer transformative fundamental and technological opportunities. Due to their high surface-to-volume ratios, nanoscale materials are extremely sensitive sensors. Likewise, peptides represent robust substrates for selective recognition due to the potential for broad chemical diversity within their relatively compact size. Here we explore the possibilities of linking peptides to nanosensors for the selective detection of biochemical targets. Such systems raise a number of interesting fundamental challenges: What are the peptide sequences, and how can rational design be used to derive selective binders? What nanomaterials should be used, and what are some strategies for assembling hybrid nanosensors? What role does molecular modeling play in elucidating response mechanisms? What is the resulting performance of these sensors, in terms of sensitivity, selectivity, and response time? What are some potential applications? This Account will highlight our early attempts to address these research challenges. Specifically, we use natural peptide sequences or sequences identified from phage display as capture elements. The sensors are based on a variety of nanomaterials including nanowires, graphene, and carbon nanotubes. We couple peptides to the nanomaterial surfaces via traditional surface functionalization methods or self-assembly. Molecular modeling provides detailed insights into the hybrid nanostructure, as well as the sensor detection mechanisms. The peptide nanosensors can distinguish chemically camouflaged mixtures of vapors and detect chemical warfare agents with sensitivities as low as parts-per-billion levels. Finally, we anticipate future uses of this technology in biomedicine: for example, devices based on these sensors could detect disease from the molecular components in human breath. Overall, these results provide a

  2. Dicyclopropylmethyl peptide backbone protectant.

    Science.gov (United States)

    Carpino, Louis A; Nasr, Khaled; Abdel-Maksoud, Adel Ali; El-Faham, Ayman; Ionescu, Dumitru; Henklein, Peter; Wenschuh, Holger; Beyermann, Michael; Krause, Eberhard; Bienert, Michael

    2009-08-20

    The N-dicyclopropylmethyl (Dcpm) residue, introduced into amino acids via reaction of dicyclopropylmethanimine hydrochloride with an amino acid ester followed by sodium cyanoborohydride or triacetoxyborohydride reduction, can be used as an amide bond protectant for peptide synthesis. Examples which demonstrate the amelioration of aggregation effects include syntheses of the alanine decapeptide and the prion peptide (106-126). Avoidance of cyclization to the aminosuccinimide followed substitution of Fmoc-(Dcpm)Gly-OH for Fmoc-Gly-OH in the assembly of sequences containing the sensitive Asp-Gly unit.

  3. Invertebrate FMRFamide related peptides.

    Science.gov (United States)

    Krajniak, Kevin G

    2013-06-01

    In 1977 the neuropeptide FMRFamide was isolated from the clam, Macrocallista nimbosa. Since then several hundred FMRFamide-related peptides (FaRPs) have been isolated from invertebrate animals. Precursors to the FaRPs likely arose in the cnidarians. With the transition to a bilateral body plan FaRPs became a fixture in the invertebrate phyla. They have come to play a critical role as neurotransmitters, neuromodulators, and neurohormones. FaRPs regulate a variety of body functions including, feeding, digestion, circulation, reproduction, movement. The evolution of the molecular form and function of these omnipresent peptides will be considered.

  4. Calcitonin blood test

    Science.gov (United States)

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

  5. Natriuretic peptides and cerebral hemodynamics

    DEFF Research Database (Denmark)

    Guo, Song; Barringer, Filippa; Zois, Nora Elisabeth;

    2014-01-01

    Natriuretic peptides have emerged as important diagnostic and prognostic tools for cardiovascular disease. Plasma measurement of the bioactive peptides as well as precursor-derived fragments is a sensitive tool in assessing heart failure. In heart failure, the peptides are used as treatment...

  6. Descriptors for antimicrobial peptides

    DEFF Research Database (Denmark)

    Jenssen, Håvard

    2011-01-01

    Introduction: A frightening increase in the number of isolated multidrug resistant bacterial strains linked to the decline in novel antimicrobial drugs entering the market is a great cause for concern. Cationic antimicrobial peptides (AMPs) have lately been introduced as a potential new class of ...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s...... combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance........c. administrations for 56 days, and glucose tolerance was assessed after one acute injection, 3 weeks of treatment, and again after 7 weeks of treatment. To assess the effect on insulin sensitivity, rats received 5 μg/kg KBP-042 for 21 days before hyperinsulinemic-euglycemic clamp. Results: KBP-042 induced a...

  8. 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.

  9. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  10. Biochemical functionalization of peptide nanotubes with phage displayed peptides.

    Science.gov (United States)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering. PMID:27479451

  11. Association of Variants in Genes Related to the Immune Response and Obesity with Benign Prostatic Hyperplasia in CLUE II

    Science.gov (United States)

    Lopez, David S.; Peskoe, Sarah B.; Tsilidis, Konstantinos K.; Hoffman-Bolton, Judy; Helzlsouer, Kathy J.; Isaacs, William B.; Smith, Michael W.; Platz, Elizabeth A.

    2014-01-01

    BACKGROUND Chronic inflammation and obesity may contribute to the genesis or progression of benign prostatic hyperplasia (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, RNASEL) and genes involved in obesity, including insulin regulation (LEP, ADIPOQ, PPARG, TCF7L2), with BPH. METHODS 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 (OR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS 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; Ptrend=0.006). CONCLUSION SNPs in genes related to immune response and obesity, especially in combination, may be associated with BPH. PMID:25224558

  12. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer

    Science.gov (United States)

    Tsilidis, Konstantinos K.; Helzlsouer, Kathy J.; Smith, Michael W.; Grinberg, Victoriya; Hoffman-Bolton, Judith; Clipp, Sandra L.; Visvanathan, Kala

    2011-01-01

    Objective and methods The association of 17 candidate single nucleotide polymorphisms (SNPs) in IL10 and other immune response genes (CRP, TLR4, IL6, IL1B, IL8, TNF, RNASEL) and genes related to obesity (PPARG, TCF7L2, ADIPOQ, LEP) with colorectal cancer was investigated. Haplotype tagging SNPs were chosen for IL10, CRP, and TLR4. Incident colorectal cancer cases (n = 208) and matched controls (n = 381) were identified between baseline in 1989 and 2003 among participants in the CLUE II cohort. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Results Compared with the AA genotype at the candidate IL10-1082 locus (rs1800896), carrying one (OR, 0.79; 95% CI, 0.53–1.18) or two (OR, 0.58; 95% CI, 0.35–0.95) G alleles, a known higher producer of the anti-inflammatory cytokine IL-10, was associated with lower risk of colorectal cancer (ptrend = 0.03). Statistically significant associations with colorectal cancer were observed for three tagSNPs in IL10 (rs1800890, rs3024496, rs3024498) and one common haplotype, but these associations were due to high linkage disequilibrium with IL10-1082. Two CRP haplotypes (global p = 0.04) and TLR4 tagSNPs (rs7873784, rs11536891), but not TLR4 haplotypes, were associated with colorectal cancer. Conclusions Our study suggests that polymorphisms in IL10, and also possibly in CRP and other genes related to immune response or obesity may be associated with colorectal cancer. PMID:19760027

  13. Radiolabelled peptides for oncological diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Boerman, Otto C.; Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Queen Mary University of London, Centre for Molecular Oncology, Barts Cancer Institute, London (United Kingdom)

    2012-02-15

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of research in nuclear medicine. The {sup 111}In-labelled somatostatin analogue octreotide (OctreoScan trademark) is the most successful radiopeptide for tumour imaging, and was the first to be approved for diagnostic use. Based on the success of these studies, other receptor-targeting peptides such as cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin (BN), chemokine receptor CXCR4 targeting peptides, and RGD peptides are currently under development or undergoing clinical trials. In this review, we discuss some of these peptides and their analogues, with regard to their potential for radionuclide imaging of tumours. (orig.)

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

    OpenAIRE

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

    2015-01-01

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

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

    OpenAIRE

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

    1996-01-01

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

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

    OpenAIRE

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

    2006-01-01

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

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

    OpenAIRE

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

    2011-01-01

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

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

    OpenAIRE

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

    2007-01-01

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

  19. CGRP blockers in migraine therapy

    DEFF Research Database (Denmark)

    Edvinsson, L

    2008-01-01

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

  20. Neuropeptides and the Microbiota-Gut-Brain Axis

    OpenAIRE

    Holzer, Peter; Farzi, Aitak

    2014-01-01

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

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

    DEFF Research Database (Denmark)

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

    1989-01-01

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

  2. Antimicrobial Peptides (AMPs

    Directory of Open Access Journals (Sweden)

    Mehrzad Sadredinamin

    2016-04-01

    Full Text Available Antimicrobial peptides (AMPs are extensive group of molecules that produced by variety tissues of invertebrate, plants, and animal species which play an important role in their immunity response. AMPs have different classifications such as; biosynthetic machines, biological sources, biological functions, molecular properties, covalent bonding patterns, three dimensional structures, and molecular targets.These molecules have multidimensional properties including antimicrobial activity, antiviral activity, antifungal activity, anti-parasite activity, biofilm control, antitumor activity, mitogens activity and linking innate to adaptive immunity that making them promising agents for therapeutic drugs. In spite of this advantage of AMPs, their clinical developments have some limitation for commercial development. But some of AMPs are under clinical trials for the therapeutic purpose such as diabetic foot ulcers, different bacterial infections and tissue damage. In this review, we emphasized on the source, structure, multidimensional properties, limitation and therapeutic applications of various antimicrobial peptides.

  3. Antimicrobial peptides in Echinoderms

    Directory of Open Access Journals (Sweden)

    C Li

    2010-05-01

    Full Text Available Antimicrobial peptides (AMPs are important immune effector molecules for invertebrates, including echinoderms, which lack a vertebrate-type adaptive immune system. Here we summarize the knowledge of such peptides in echinoderms. Strongylocins are a novel family of cysteine-rich AMPs, recently identified in the sea urchins, Strongylocentrotus droebachiensis and S. purpuratus. Although these molecules present diverse amino acid sequences, they share an identical cysteine arrangement pattern, dissimilar to other known AMPs. A family of heterodimeric AMPs, named centrocins, are also present in S. droebachiensis. Lysozymes and fragments of larger proteins, such as beta-thymocins, actin, histone 2A and filamin A have also been shown to display antimicrobial activities in echinoderms. Future studies on AMPs should be aimed in revealing how echinoderms use these AMPs in the immune response against microbial pathogens.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  5. Expression and Its Regulation of KiSS-1 Gene Related with Reproduction%KiSS-1基因与生殖相关的表达及其调节

    Institute of Scientific and Technical Information of China (English)

    王军; 孙蕾; 常喆

    2011-01-01

    Recently, it has been found that KiSS-1 gene plays important roles in mammalian reproduction. Kisspeptin, the peptide product of the KiSS-1 gene has been shown to be powerful stimulators of the gonadotropin. Recent advances of expression of KiSS-1 gene related with reproduction and its regulation of hypothalamic expression by sex steroid hormones, metabolic hormone and photoperiod were reviewed in this paper for providing a reference for the direction of further study of KiSS-1 gene.%最近研究发现,KiSS-1基因在哺乳动物生殖内分泌的调节中具有重要作用,其编码的产物——kisspeptin能够强有力地刺激促性腺激素的分泌.笔者综述了KiSS-1基因与生殖相关的表达及性腺类固醇激素、代谢激素与光周期对其在下丘脑表达调节的最新研究进展,为今后KiSS-1基因的研究取向提供参考.

  6. The PeptideAtlas Project

    OpenAIRE

    Deutsch, Eric W.

    2010-01-01

    PeptideAtlas is a multi-species compendium of peptides observed with tandem mass spectrometry methods. Raw mass spectrometer output files are collected from the community and reprocessed through a uniform analysis and validation pipeline that continues to advance. The results are loaded into a database and the information derived from the raw data is returned to the community via several web-based data exploration tools. The PeptideAtlas resource is useful for experiment planning, improving g...

  7. Human Antimicrobial Peptides and Proteins

    OpenAIRE

    Guangshun Wang

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified ...

  8. Discovery of genes related to witches broom disease in Paulownia tomentosa × Paulownia fortunei by a De Novo assembled transcriptome.

    Directory of Open Access Journals (Sweden)

    Rongning Liu

    Full Text Available In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches' Broom (PaWB disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina. 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene's roles in the developmental process and in PaWB disease resistance.

  9. Discovery of genes related to witches broom disease in Paulownia tomentosa × Paulownia fortunei by a De Novo assembled transcriptome.

    Science.gov (United States)

    Liu, Rongning; Dong, Yanpeng; Fan, Guoqiang; Zhao, Zhenli; Deng, Minjie; Cao, Xibing; Niu, Suyan

    2013-01-01

    In spite of its economic importance, very little molecular genetics and genomic research has been targeted at the family Paulownia spp. The little genetic information on this plant is a big obstacle to studying the mechanisms of its ability to resist Paulownia Witches' Broom (PaWB) disease. Analysis of the Paulownia transcriptome and its expression profile data are essential to extending the genetic resources on this species, thus will greatly improves our studies on Paulownia. In the current study, we performed the de novo assembly of a transcriptome on P. tomentosa × P. fortunei using the short-read sequencing technology (Illumina). 203,664 unigenes with a mean length of 1,328 bp was obtained. Of these unigenes, 32,976 (30% of all unigenes) containing complete structures were chosen. Eukaryotic clusters of orthologous groups, gene orthology, and the Kyoto Encyclopedia of Genes and Genomes annotations were performed of these unigenes. Genes related to PaWB disease resistance were analyzed in detail. To our knowledge, this is the first study to elucidate the genetic makeup of Paulownia. This transcriptome provides a quick way to understanding Paulownia, increases the number of gene sequences available for further functional genomics studies and provides clues to the identification of potential PaWB disease resistance genes. This study has provided a comprehensive insight into gene expression profiles at different states, which facilitates the study of each gene's roles in the developmental process and in PaWB disease resistance. PMID:24278262

  10. Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro.

    Science.gov (United States)

    Gong, Zijian; Lai, Wei; Liu, Min; Hua, Zhengshuang; Sun, Yayin; Xu, Qingfang; Xia, Yue; Zhao, Yue; Xie, Xiaoyuan

    2016-04-01

    The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation inpenA(A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance ofNeisseria gonorrhoeaeto ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry. PMID:26787702

  11. Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro.

    Science.gov (United States)

    Gong, Zijian; Lai, Wei; Liu, Min; Hua, Zhengshuang; Sun, Yayin; Xu, Qingfang; Xia, Yue; Zhao, Yue; Xie, Xiaoyuan

    2016-04-01

    The emergence of ceftriaxone-resistantNeisseria gonorrhoeaeis currently a global public health concern. However, the mechanism of ceftriaxone resistance is not yet fully understood. To investigate the potential genes related to ceftriaxone resistance inNeisseria gonorrhoeae, we subcultured six gonococcal strains with increasing concentrations of ceftriaxone and isolated the strains that became resistant. After analyzing several frequently reported genes involved in ceftriaxone resistance, we found only a single mutation inpenA(A501V). However, differential analysis of the genomes and transcriptomes between pre- and postselection strains revealed many other mutated genes as well as up- and downregulated genes. Transformation of the mutatedpenAgene into nonresistant strains increased the MIC between 2.0- and 5.3-fold, and transformation of mutatedftsXincreased the MIC between 3.3- and 13.3-fold. Genes encoding the ABC transporters FarB, Tfq, Hfq, and ExbB were overexpressed, whilepilM,pilN, andpilQwere downregulated. Furthermore, the resistant strain developed cross-resistance to penicillin and cefuroxime, had an increased biochemical metabolic rate, and presented fitness defects such as prolonged growth time and downregulated PilMNQ. In conclusion, antimicrobial pressure could result in the emergence of ceftriaxone resistance, and the evolution of resistance ofNeisseria gonorrhoeaeto ceftriaxone is a complicated process at both the pretranscriptional and posttranscriptional levels, involving several resistance mechanisms of increased efflux and decreased entry.

  12. Peptides that influence membrane topology

    Science.gov (United States)

    Wong, Gerard C. L.

    2014-03-01

    We examine the mechanism of a range of polypeptides that influence membrane topology, including antimicrobial peptides, cell penetrating peptides, viral fusion peptides, and apoptosis proteins, and show how a combination of geometry, coordination chemistry, and soft matter physics can be used to approach a unified understanding. We will also show how such peptides can impact biomedical problems such as auto-immune diseases (psoriasis, lupus), infectious diseases (viral and bacterial infections), and mitochondrial pathologies (under-regulated apoptosis leads to neurodegenerative diseases whereas over-regulated apoptosis leads to cancer.)

  13. NCAM Mimetic Peptides: An Update

    DEFF Research Database (Denmark)

    Berezin, Vladimir; Bock, Elisabeth

    2008-01-01

    sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling a number of peptides derived from NCAM and targeting NCAM heterophilic ligands such as the fibroblast growth factor receptor...... and heparan sulfate proteoglycans (HSPG) have been identified. The FGL, dekaCAM, FRM/EncaminA, BCL, EncaminC and EncaminE peptides all target the FGF receptor whereas the heparin binding peptide HBP targets HSPG. Moreover, a number of NCAM binding peptides have been identified employing screening...

  14. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology. PMID:26279082

  15. Improving Peptide Applications Using Nanotechnology.

    Science.gov (United States)

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  16. Biodiscovery of aluminum binding peptides

    Science.gov (United States)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

    2013-05-01

    Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

  17. A Review on the Association between Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Wei-Yih Chiu

    2012-01-01

    Full Text Available There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1 analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC, but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.

  18. A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

    Science.gov (United States)

    Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

    2016-09-15

    A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens. PMID:27285778

  19. Polyclonal Peptide Antisera.

    Science.gov (United States)

    Pihl, Tina H; Illigen, Kristin E; Houen, Gunnar

    2015-01-01

    Polyclonal antibodies are relatively easy to produce and may supplement monoclonal antibodies for some applications or even have some advantages. The choice of species for production of (peptide) antisera is based on practical considerations, including availability of immunogen (vaccine) and animals. Two major factors govern the production of antisera: the nature of adaptive immune responses, which take place over days/weeks and ethical guidelines for animal welfare. Here, simple procedures for immunization of mice, rabbits, sheep, goats, pigs, horses, and chickens are presented. PMID:26424267

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Mapping of DNA sex-specific markers and genes related to sex differentiation in turbot (Scophthalmus maximus).

    Science.gov (United States)

    Viñas, Ana; Taboada, Xoana; Vale, Luis; Robledo, Diego; Hermida, Miguel; Vera, Manel; Martínez, Paulino

    2012-10-01

    Production of all-female populations in turbot can increase farmer's benefits since sexual dimorphism in growth in this species is among the highest within marine fish, turbot females reaching commercial size 3-6 months earlier than males. Puberty in males occurs earlier than in females, which additionally slows their growth. Thus, elucidating the mechanisms of sex determination and gonad differentiation is a relevant goal for turbot production. A ZZ/ZW sex determination mechanism has been suggested for this species, and four sex-related quantitative trait loci (QTL) were detected, the major one located in linkage group (LG) 5 and the three minor ones in LG6, LG8, and LG21. In the present work, we carried out a linkage analysis for several sex-related markers: (1) three anonymous sex-associated RAPD and (2) several candidate genes related to sex determination and gonad differentiation in other species (Sox3, Sox6, Sox8, Sox9, Sox17, Sox19, Amh, Dmrta2, Cyp19a, Cyp19b). We focused our attention on their co-localization with the major and minor sex-related QTL trying to approach to the master sex-determining gene of this species. Previously described growth-related QTL were also considered since the association observed between growth and sex determination in fish. Amh, Dmrta2, and one RAPD were located in LG5, while Sox9 and Sox17 (LG21), Cyp19b (LG6), and a second RAPD (LG8) co-mapped with suggestive sex-related QTL, thus supporting further analyses on these genes to elucidate the genetic basis of this relevant trait for turbot farming. PMID:22552957

  2. The Source of Genes Related to Rice Grain Starch Synthesis Among Cultivated Varieties and Its Contribution to Quality

    Institute of Scientific and Technical Information of China (English)

    YAN Chang-jie; TIAN Shun; ZHANG Zheng-qiu; HAN Yue-peng; CHEN Feng; LI Xin; GU Ming-hong

    2007-01-01

    The property of starch in rice grain endosperm is a very important determinant for rice quality, and it is essential to understand the genetic effect of the genes related to starch synthesis in high-yielding rice varieties for rice quality improvement. The physicochemical properties (e.g., amylose content, gel consistency, and RVA profile) were assessed on 53 rice varieties, including certain typical indica/japonica landraces and certain high-yielding modern varieties. And molecular markers for Sbel, Sbe3 developed on the basis of sequence diversities between the rice subspecies indica and japonica, together with PCR-Acc Ⅰ marker for Wx gene were used to investigate the genotypes of 53 rice cultivars. The result showed that the developed molecular markers for Wx, Sbel, Sbe3 could distinguish indica or japonica alleles at three loci. Among all the 53 rice cultivars, six genotypes were observed when Sbel, Sbe3, and Wx loci were considered together, while the genotypes of WxiSbeljSbe3i and WxiSbeljSbe3j were absent. In order to explore the genetic effects of the three genes, especially for starch branching enzyme genes, ANOVA and multiple comparison analysis were conducted.The results showed that rice cultivars with different genotypes exhibited different phenotypes, including amylose content,gel consistency and certain RVA characteristics, and the significant differences among the six genotypes were observed.It was concluded that these three genes had randomly recombined during the process of the rice variety development.And the genetic effects of indica and japonica alleles at three gene loci were different, of which, Wx gene plays a major role in determining the starch properties, followed by Sbel and Sbe3, and the genetic effects of Sbel and Sbe3 in different backgrounds (Wxi, Wxj) are different. The results have provided a clue for rice good quality variety development, and the molecular markers will benefit to the improvement in quality of rice.

  3. Global identification of genes related to nutrient deficiency in intervertebral disc cells in an experimental nutrient deprivation model.

    Directory of Open Access Journals (Sweden)

    Hideki Sudo

    Full Text Available BACKGROUND: Intervertebral disc degeneration is a significant cause of degenerative spinal diseases. Nucleus pulposus (NP cells reportedly fail to survive in large degenerated discs with limited nutrient availability. Therefore, understanding the regulatory mechanism of the molecular response of NP cells to nutrient deprivation may reveal a new strategy to treat disc degeneration. This study aimed to identify genes related to nutrient deprivation in NP cells on a global scale in an experimental nutrient deprivation model. METHODOLOGY/PRINCIPAL FINDINGS: Rat NP cells were subjected to serum starvation. Global gene expression was profiled by microarray analysis. Confirmation of the selected genes was obtained by real-time polymerase chain reaction array analysis. Western blotting was used to confirm the expression of selected genes. Functional interactions between p21(Cip1 and caspase 3 were examined. Finally, flow cytometric analyses of NP cells were performed. Microarray analysis revealed 2922 differentially expressed probe sets with ≥1.5-fold changes in expression. Serum starvation of NP cells significantly affected the expression of several genes involved in DNA damage checkpoints of the cell cycle, including Atm, Brca1, Cdc25, Gadd45, Hus1, Ppm1D, Rad 9, Tp53, and Cyclin D1. Both p27(Kip1 and p53 protein expression was upregulated in serum-starved cells. p21(Cip1 expression remained in NP cells transfected with short interfering RNA targeting caspase 3 (caspase 3 siRNA. Both G1 arrest and apoptosis induced by serum starvation were inhibited in cells transfected with caspase 3 siRNA. CONCLUSIONS/SIGNIFICANCE: Nutrient deprivation in NP cells results in the activation of a signaling response including DNA damage checkpoint genes regulating the cell cycle. These results provide novel possibilities to improve the success of intervertebral disc regenerative techniques.

  4. Radiolabelled peptides for oncological diagnosis.

    NARCIS (Netherlands)

    Laverman, P.; Sosabowski, J.K.; Boerman, O.C.; Oyen, W.J.G.

    2012-01-01

    Radiolabelled receptor-binding peptides targeting receptors (over)expressed on tumour cells are widely under investigation for tumour diagnosis and therapy. The concept of using radiolabelled receptor-binding peptides to target receptor-expressing tissues in vivo has stimulated a large body of resea

  5. Urinary Peptides in Rett Syndrome.

    Science.gov (United States)

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  6. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptide...

  7. Solid-phase peptide synthesis

    DEFF Research Database (Denmark)

    Jensen, Knud Jørgen

    2013-01-01

    This chapter provides an introduction to and overview of peptide chemistry with a focus on solid-phase peptide synthesis. The background, the most common reagents, and some mechanisms are presented. This chapter also points to the different chapters and puts them into perspective....

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

    Institute of Scientific and Technical Information of China (English)

    王烨明; 曾炳芳; 李晓林

    2007-01-01

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

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

    Science.gov (United States)

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

    1991-05-01

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

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

    Science.gov (United States)

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

    2016-06-01

    Spray freeze drying was developed to produce dry powders suitable for applications such as inhalation delivery. In the current study, the spray freeze drying technique was employed to produce inhalable salmon calcitonin microparticles. Effects of the carrier type, concentration of hydroxyl propyl-β-cyclodextrin and the presence of Tween 80 on the chemical and structural stability, as well as on the aerosol performance of the particles were investigated. The results indicated that hydroxyl propyl-β-cyclodextrin had the most important effect on the chemical stability of the powder and strongly increased its stability by increasing its concentration in the formulation. Chemically stable formulations (over 90 % recovery) were selected for further examinations. Fluorescence spectroscopy and circular dichroism suggested that the formulations were structurally stable. Aerosol performance showed that the Tween-free powders produced higher fine particle fraction values than the formulations containing Tween (53.7 vs. 41.92 % for trehalose content and 52.85 vs. 43.06 % for maltose content). PMID:27279064

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

    Directory of Open Access Journals (Sweden)

    Poursina Narges

    2016-06-01

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

  12. Conus venom peptide pharmacology.

    Science.gov (United States)

    Lewis, Richard J; Dutertre, Sébastien; Vetter, Irina; Christie, MacDonald J

    2012-04-01

    Conopeptides are a diverse group of recently evolved venom peptides used for prey capture and/or defense. Each species of cone snails produces in excess of 1000 conopeptides, with those pharmacologically characterized (≈ 0.1%) targeting a diverse range of membrane proteins typically with high potency and specificity. The majority of conopeptides inhibit voltage- or ligand-gated ion channels, providing valuable research tools for the dissection of the role played by specific ion channels in excitable cells. It is noteworthy that many of these targets are found to be expressed in pain pathways, with several conopeptides having entered the clinic as potential treatments for pain [e.g., pyroglutamate1-MrIA (Xen2174)] and one now marketed for intrathecal treatment of severe pain [ziconotide (Prialt)]. This review discusses the diversity, pharmacology, structure-activity relationships, and therapeutic potential of cone snail venom peptide families acting at voltage-gated ion channels (ω-, μ-, μO-, δ-, ι-, and κ-conotoxins), ligand-gated ion channels (α-conotoxins, σ-conotoxin, ikot-ikot, and conantokins), G-protein-coupled receptors (ρ-conopeptides, conopressins, and contulakins), and neurotransmitter transporters (χ-conopeptides), with expanded discussion on the clinical potential of sodium and calcium channel inhibitors and α-conotoxins. Expanding the discovery of new bioactives using proteomic/transcriptomic approaches combined with high-throughput platforms and better defining conopeptide structure-activity relationships using relevant membrane protein crystal structures are expected to grow the already significant impact conopeptides have had as both research probes and leads to new therapies. PMID:22407615

  13. Potential of phage-displayed peptide library technology to identify functional targeting peptides

    Science.gov (United States)

    Krumpe, Lauren RH; Mori, Toshiyuki

    2010-01-01

    Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. PMID:20150977

  14. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  15. Aliphatic peptides show similar self-assembly to amyloid core sequences, challenging the importance of aromatic interactions in amyloidosis.

    Science.gov (United States)

    Lakshmanan, Anupama; Cheong, Daniel W; Accardo, Angelo; Di Fabrizio, Enzo; Riekel, Christian; Hauser, Charlotte A E

    2013-01-01

    The self-assembly of abnormally folded proteins into amyloid fibrils is a hallmark of many debilitating diseases, from Alzheimer's and Parkinson diseases to prion-related disorders and diabetes type II. However, the fundamental mechanism of amyloid aggregation remains poorly understood. Core sequences of four to seven amino acids within natural amyloid proteins that form toxic fibrils have been used to study amyloidogenesis. We recently reported a class of systematically designed ultrasmall peptides that self-assemble in water into cross-β-type fibers. Here we compare the self-assembly of these peptides with natural core sequences. These include core segments from Alzheimer's amyloid-β, human amylin, and calcitonin. We analyzed the self-assembly process using circular dichroism, electron microscopy, X-ray diffraction, rheology, and molecular dynamics simulations. We found that the designed aliphatic peptides exhibited a similar self-assembly mechanism to several natural sequences, with formation of α-helical intermediates being a common feature. Interestingly, the self-assembly of a second core sequence from amyloid-β, containing the diphenylalanine motif, was distinctly different from all other examined sequences. The diphenylalanine-containing sequence formed β-sheet aggregates without going through the α-helical intermediate step, giving a unique fiber-diffraction pattern and simulation structure. Based on these results, we propose a simplified aliphatic model system to study amyloidosis. Our results provide vital insight into the nature of early intermediates formed and suggest that aromatic interactions are not as important in amyloid formation as previously postulated. This information is necessary for developing therapeutic drugs that inhibit and control amyloid formation. PMID:23267112

  16. Peptide primary messengers in plants

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The peptide primary messengers regulate embryonic development,cell growth and many other activities in animal cells. But recent evidence verified that peptide primary messengers are also involved in plant defense responses, the recognition between pollen and stigma and keep the balance between cell proliferation and differentiations in shoot apical meristems. Those results suggest that plants may actually make wide use of peptide primary messengers, both in embryonic development and late life when they rally their cells to defend against pathogens and insect pests. The recent advance in those aspects is reviewed.

  17. Screening of TACE Peptide Inhibitors from Phage Display Peptide Library

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To obtain the recombinant tumor necrosis factor-α converting enzyme (TACE) ectodomain and use it as a selective molecule for the screening of TACE peptide inhibitors, the cDNA coding catalytic domain (T800) and full-length ectodomain (T1300) of TACE were amplified by RTPCR, and the expression plasmids were constructed by inserting T800 and T1300 into plasmid pET28a and pET-28c respectively. The recombinant T800 and T1300 were induced by IPTG, and SDSPAGE and Western blotting analysis results revealed that T800 and T1300 were highly expressed in the form of inclusion body. After Ni2+-NTA resin affinity chromatography, the recombinant proteins were used in the screening of TACE-binding peptides from phage display peptide library respectively. After 4 rounds of biopanning, the positive phage clones were analyzed by ELISA, competitive inhibition assay and DNA sequencing. A common amino acid sequence (TRWLVYFSRPYLVAT) was found and synthesized. The synthetic peptide could inhibit the TNF-α release from LPS-stimulated human peripheral blood mononuclear cells (PBMC) up to 60.3 %. FACS analysis revealed that the peptide mediated the accumulation of TNF-α on the cell surface. These results demonstrate that the TACE-binding peptide is an effective antagonist of TACE.

  18. New vasoactive peptides in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Goetze, Jens Peter; Bendtsen, Flemming;

    2014-01-01

    BACKGROUND: Patients with cirrhosis have substantial circulatory imbalance between vasoconstrictive and vasodilating forces. The study of circulatory vasoactive peptides may provide important pathophysiological information. This study aimed to assess concentrations, organ extraction and relations...

  19. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte;

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...... improve biomolecular recognition by synthetic nucleic acid analogues. Circular dichroism (CD) measurements showed no distortion of the duplex structure by the incorporated peptide chains while studies in human serum indicated superior stability of the POCs compared to LNA/DNA mixmers and unmodified DNA...

  20. Peptide nanostructures in biomedical technology.

    Science.gov (United States)

    Feyzizarnagh, Hamid; Yoon, Do-Young; Goltz, Mark; Kim, Dong-Shik

    2016-09-01

    Nanostructures of peptides have been investigated for biomedical applications due to their unique mechanical and electrical properties in addition to their excellent biocompatibility. Peptides may form fibrils, spheres and tubes in nanoscale depending on the formation conditions. These peptide nanostructures can be used in electrical, medical, dental, and environmental applications. Applications of these nanostructures include, but are not limited to, electronic devices, biosensing, medical imaging and diagnosis, drug delivery, tissue engineering and stem cell research. This review offers a discussion of basic synthesis methods, properties and application of these nanomaterials. The review concludes with recommendations and future directions for peptide nanostructures. WIREs Nanomed Nanobiotechnol 2016, 8:730-743. doi: 10.1002/wnan.1393 For further resources related to this article, please visit the WIREs website. PMID:26846352

  1. Targeting cancer with peptide aptamers

    OpenAIRE

    Seigneuric, Renaud; Gobbo, Jessica; Colas, Pierre; Garrido, Carmen

    2011-01-01

    A major endeavour in cancer chemotherapy is to develop agents that specifically target a biomolecule of interest. There are two main classes of targeting agents: small molecules and biologics. Among biologics (e.g.: antibodies), DNA, RNA but also peptide aptamers are relatively recent agents. Peptide aptamers are seldom described but represent attractive agents that can inhibit a growing panel of oncotargets including Heat Shock Proteins. Potential pitfalls and coming challenges towards succe...

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

    Directory of Open Access Journals (Sweden)

    Selma Cristina Cury Camargo

    2004-03-01

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

  3. Peptides and proteins

    Energy Technology Data Exchange (ETDEWEB)

    Bachovchin, W.W.; Unkefer, C.J.

    1994-12-01

    Advances in magnetic resonance and vibrational spectroscopy make it possible to derive detailed structural information about biomolecular structures in solution. These techniques are critically dependent on the availability of labeled compounds. For example, NMR techniques used today to derive peptide and protein structures require uniformity {sup 13}C-and {sup 15}N-labeled samples that are derived biosynthetically from (U-6-{sup 13}C) glucose. These experiments are possible now because, during the 1970s, the National Stable Isotope Resource developed algal methods for producing (U-6-{sup 13}C) glucose. If NMR techniques are to be used to study larger proteins, we will need sophisticated labelling patterns in amino acids that employ a combination of {sup 2}H, {sup 13}C, and {sup 15}N labeling. The availability of these specifically labeled amino acids requires a renewed investment in new methods for chemical synthesis of labeled amino acids. The development of new magnetic resonance or vibrational techniques to elucidate biomolecular structure will be seriously impeded if we do not see rapid progress in labeling technology. Investment in labeling chemistry is as important as investment in the development of advanced spectroscopic tools.

  4. Kinins and peptide receptors.

    Science.gov (United States)

    Regoli, Domenico; Gobeil, Fernand

    2016-04-01

    This paper is divided into two sections: the first contains the essential elements of the opening lecture presented by Pr. Regoli to the 2015 International Kinin Symposium in S. Paulo, Brazil on June 28th and the second is the celebration of Dr. Regoli's 60 years of research on vasoactive peptides. The cardiovascular homeostasis derives from a balance of two systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS). The biologically active effector entity of RAS is angiotensin receptor-1 (AT-1R), and that of KKS is bradykinin B2 receptor (B2R). The first mediates vasoconstriction, the second is the most potent and efficient vasodilator. Thanks to its complex and multi-functional mechanism of action, involving nitric oxide (NO), prostacyclin and endothelial hyperpolarizing factor (EDHF). B2R is instrumental for the supply of blood, oxygen and nutrition to tissues. KKS is present on the vascular endothelium and functions as an autacoid playing major roles in cardiovascular diseases (CVDs) and diabetes. KKS exerts a paramount role in the prevention of thrombosis and atherosclerosis. Such knowledge emphasizes the already prominent value of the ACE-inhibitors (ACEIs) for the treatment of CVDs and diabetes. Indeed, the ACEIs, thanks to their double action (block of the RAS and potentiation of the KKS) are the ideal agents for a rational treatment of these diseases. PMID:26408609

  5. Antimicrobial peptides in annelids

    Directory of Open Access Journals (Sweden)

    A Tasiemski

    2008-06-01

    Full Text Available Gene encoded antimicrobial peptides (AMPs are widely distributed among living organisms including plants, invertebrates and vertebrates. They constitute important effectors of the innate immune response by exerting multiple roles as mediators of inflammation with impact on epithelial and inflammatory cells influencing diverse processes such as cytokine release, cell proliferation, angiogenesis, wound healing, chemotaxis and immune induction. In invertebrates, most of the data describe the characterization and/or the function of AMPs in the numerically and economically most representative group which are arthropods. Annelids are among the first coelomates and are therefore of special phylogenetic interest. Compared to other invertebrate groups, data on annelid’s immunity reveal heavier emphasis on the cellular than on the humoral response suggesting that immune defense of annelids seems to be principally developed as cellular immunity.This paper gives an overview of the variety of AMPs identified in the three classes of annelids, i.e. polychaetes, oligochaetes and achaetes. Their functions, when they have been studied, in the humoral or cellular response of annelids are also mentioned.

  6. Antimicrobial peptides in crustaceans

    Directory of Open Access Journals (Sweden)

    RD Rosa

    2010-11-01

    Full Text Available Crustaceans are a large and diverse invertebrate animal group that mounts a complex and efficient innate immune response against a variety of microorganisms. The crustacean immune system is primarily related to cellular responses and the production and release of important immune effectors into the hemolymph. Antimicrobial proteins and/or peptides (AMPs are key components of innate immunity and are widespread in nature, from bacteria to vertebrate animals. In crustaceans, 15 distinct AMP families are currently recognized, although the great majority (14 families comes from members of the order Decapoda. Crustacean AMPs are generally cationic, gene-encoded molecules that are mainly produced by circulating immune-competent cells (hemocytes or are derived from unrelated proteins primarily involved in other biological functions. In this review, we tentatively classified the crustacean AMPs into four main groups based on their amino acid composition, structural features and multi-functionality. We also attempted to summarize the current knowledge on their implication both in an efficient response to microbial infections and in crustacean survival.

  7. Material Binding Peptides for Nanotechnology

    Directory of Open Access Journals (Sweden)

    Urartu Ozgur Safak Seker

    2011-02-01

    Full Text Available Remarkable progress has been made to date in the discovery of material binding peptides and their utilization in nanotechnology, which has brought new challenges and opportunities. Nowadays phage display is a versatile tool, important for the selection of ligands for proteins and peptides. This combinatorial approach has also been adapted over the past decade to select material-specific peptides. Screening and selection of such phage displayed material binding peptides has attracted great interest, in particular because of their use in nanotechnology. Phage display selected peptides are either synthesized independently or expressed on phage coat protein. Selected phage particles are subsequently utilized in the synthesis of nanoparticles, in the assembly of nanostructures on inorganic surfaces, and oriented protein immobilization as fusion partners of proteins. In this paper, we present an overview on the research conducted on this area. In this review we not only focus on the selection process, but also on molecular binding characterization and utilization of peptides as molecular linkers, molecular assemblers and material synthesizers.

  8. Collagen-like antimicrobial peptides.

    Science.gov (United States)

    Masuda, Ryo; Kudo, Masakazu; Dazai, Yui; Mima, Takehiko; Koide, Takaki

    2016-11-01

    Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016. PMID:27271210

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

    International Nuclear Information System (INIS)

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

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

    International Nuclear Information System (INIS)

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

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Baldini Enke

    2013-02-01

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

  13. 应用A549细胞单层模型研究蛋白多肽类药物肺部吸收的特性%Transport of proteins and peptides across human cultured alveolar A549 cell monolayers

    Institute of Scientific and Technical Information of China (English)

    王智瑛; 张悦; 张强

    2004-01-01

    Aim An in vitro cultured monolayer system of alveolar epithelial cells was used as a model to investigate the transport pathway peptides or proteins, salmon calcitonin (sCT), insulin (INS), recombinant hirudin (rHAV2), and recombinant human growth hormone (rhGH), in pulmonary epithelium in vivo. Methods Human lung adenocareinoma A549 cells formed continuous monolayers with growing polycarbonate filters of Transwell plate. Transport studies of macromolecules in the monolayer system were carried out after 6 days in culture. The transport of peptides or proteins with MW 3 400 - 22 000 was studied in cultured human lung adenocareinoma A549 cell monolayers at different conditions. Results The results showed that the apparent permeability coefficients (Papp) of these macromolecules across A549 cell monolayers ranged from 2×10-6 to 5×10-6 cm·s-1 and exhibited good inverse correlation with molecule weight. No concentration, direction and temperature dependence were observed in the permeation of sCT, INS and rHAV2. While the Papp of rhGH in the BA direction (2.25×10-6 cm·s-1) was significantly less than that in the reverse direction. ThePapp values of rhGH were concentration and temperature independent in the AB direction. Conclusion These findings suggest that the hydrophilic peptides and proteins, salmon calcitonin, insulin, recombinant hirudin, and recombinant human growth hormone used in this study, appeared to penetrate the A549 cell monolayers via a paracellular pathway by passive diffusion mechanism.

  14. Automated solid-phase peptide synthesis to obtain therapeutic peptides

    Directory of Open Access Journals (Sweden)

    Veronika Mäde

    2014-05-01

    Full Text Available The great versatility and the inherent high affinities of peptides for their respective targets have led to tremendous progress for therapeutic applications in the last years. In order to increase the drugability of these frequently unstable and rapidly cleared molecules, chemical modifications are of great interest. Automated solid-phase peptide synthesis (SPPS offers a suitable technology to produce chemically engineered peptides. This review concentrates on the application of SPPS by Fmoc/t-Bu protecting-group strategy, which is most commonly used. Critical issues and suggestions for the synthesis are covered. The development of automated methods from conventional to essentially improved microwave-assisted instruments is discussed. In order to improve pharmacokinetic properties of peptides, lipidation and PEGylation are described as covalent conjugation methods, which can be applied by a combination of automated and manual synthesis approaches. The synthesis and application of SPPS is described for neuropeptide Y receptor analogs as an example for bioactive hormones. The applied strategies represent innovative and potent methods for the development of novel peptide drug candidates that can be manufactured with optimized automated synthesis technologies.

  15. Peptides and Food Intake

    Directory of Open Access Journals (Sweden)

    Carmen Sobrino Crespo

    2014-04-01

    Full Text Available Nutrients created by the digestion of food are proposed to active G protein coupled receptors on the luminal side of enteroendocrine cells e.g. the L-cell. This stimulates the release of gut hormones. Hormones released from the gut and adipose tissue play an important rol in the regulation of food intake and energy expenditure (1.Many circulating signals, including gut hormones, can influence the activity of the arcuate nucleus (ARC neurons directly, after passing across the median eminence. The ARC is adjacent to the median eminence, a circumventricular organ with fenestrated capillaries and hence an incomplete blood-brain barrier (2. The ARC of the hypothalamus is believed to play a crucial role in the regulation of food intake and energy homeostasis. The ARC contains two populations of neurons with opposing effect on food intake (3. Medially located orexigenic neurons (i.e those stimulating appetite express neuropeptide Y (NPY and agouti-related protein (AgRP (4-5. Anorexigenic neurons (i.e. those inhibiting appetite in the lateral ARC express alpha-melanocyte stimulating hormone (α-MSH derived from pro-opiomelanocortin (POMC and cocaine and amphetamine-regulated transcript (CART (6. The balance between activities of these neuronal circuits is critical to body weight regulation.In contrast, other peripheral signals influence the hypothalamus indirectly via afferent neuronal pathway and brainstem circuits. In this context gastrointestinal’s vagal afferents are activated by mechanoreceptors and chemoreceptors, and converge in the nucleus of the tractus solitaries (NTS of the brainstem. Neuronal projections from the NTS, in turn, carry signals to the hypotalamus (1, 7. Gut hormones also alter the activity of the ascending vagal pathway from the gut to the brainstem. In the cases of ghrelin and Peptide tyrosine tyrosine (PYY, there are evidences for both to have a direct action on the arcuate nucleus and an action via the vagus nerve a

  16. N-三甲基壳聚糖包覆的降钙素脂质体的制备及其体内外黏附性质研究%Study on Preparation of N-trimethyl Chitosan Coated Calcitonin Liposome and Adhesion Properties of It in vivo and in vitro

    Institute of Scientific and Technical Information of China (English)

    黄爱文; 竹内洋文; 宋洪涛

    2013-01-01

    TMC liposomes to duodenum,jejunum,ileum were investigated by C6 labeling.RESULTS:The degree of quatemization for synthesized TMC was 78.10%; the prepared uncoated calcitonin liposome showed strong negative charge,and charge reversal was achieved after coated with TMC; prepared liposomes was round in appearance and coated obviously with particle size of 262.9 nm,polydispersity index of 0.172,Zeta potential of (35.8 ± 1.2) mV and entrapment efficiency of (89.14 ± 3.1)%; TMC liposomes adhered to mucin nanoparticles under pH 4.5 and pH 6.8 conditions,and reduced the Zeta potential.In rats,at 2 h,most of TMC coated liposome adhered to upper part of small intestinal,especially the duodenum,while less of it adhered to ileum; at 4 h,TMC liposome still adhered to each intestinal segment,but the symptom relieved significantly compared to 2 h,and more adhesion was found in substrate side of the ileum.CONCLUSIONS:TMC coated liposomes show good biological adhesion performance,and can be used as carrier of oral delivery of peptide drugs to carry out further study.

  17. Peptides: A new class of anticancer drugs

    Directory of Open Access Journals (Sweden)

    Ryszard Smolarczyk

    2009-07-01

    Full Text Available Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined.

  18. Perspectives and Peptides of the Next Generation

    Science.gov (United States)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  19. Exploration of the Medicinal Peptide Space.

    Science.gov (United States)

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs. PMID:26876881

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

    Science.gov (United States)

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

    2013-01-01

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

  1. Innervation of the human middle meningeal artery

    DEFF Research Database (Denmark)

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

    1998-01-01

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

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

    DEFF Research Database (Denmark)

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

    2001-01-01

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

  3. Peptide Vaccine: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Weidang Li

    2014-07-01

    Full Text Available Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

  4. Recent development of peptide self-assembly

    Institute of Scientific and Technical Information of China (English)

    Xiubo Zhao; Fang Pan; Jian R. Lu

    2008-01-01

    Amino acids are the building blocks to build peptides and proteins. Recent development in peptide synthesis has however enabled us to mimic this natural process by preparing various long and short peptides possessing different conformations and biological functions. The self-assembly of short designed peptides into molecular nanostructures is becoming a growing interest in nanobiotechnology. Self-assembled peptides exhibit several attractive features for applications in tissue regeneration, drug delivery, biological surface engineering as well as in food science, cosmetic industry and antibiotics. The aim of this review is to introduce the readers to a number of representative studies on peptide self-assembly.

  5. Antiviral active peptide from oyster

    Science.gov (United States)

    Zeng, Mingyong; Cui, Wenxuan; Zhao, Yuanhui; Liu, Zunying; Dong, Shiyuan; Guo, Yao

    2008-08-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster ( Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10 5 kDa, 5 1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10 5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  6. Antiviral active peptide from oyster

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster (Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10-5 kDa, 5-1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10?5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  7. Radioactive labelling of peptidic hormones

    International Nuclear Information System (INIS)

    The labelling of peptidic hormones requires stability, specificity and sensitivity of the label. Introduction of a radioactive atome is one way to satisfy these criteria. Several processes have been described to prepare radioactive TRF: synthesis of the peptide with labelled aminoacids or introduction of the label into the hormone. In that approach, tritium can be substituted in the imidazole ring, via precursors activating the proper carbon. Monoiodo TRF leads essentially to tritium labelling of the 5 positions whereas monoazo TRF allows the preparation of 3H TRF labelled in the 2 positions. Di-substituted TRF leads to labelling into the 2 and 5 carbons. Labelled analogs of TRF can be prepared with labelled iodine; further developments of peptide labelling, will be presented. In particular, the homolytic scission of the C-iodine, bond by photochemical activation. The nascent carbon radical can be stabilized by a tritiated scavenger. This approach eliminates the use of heavy metal catalysts

  8. 降钙素原在全身炎症反应综合征中的临床价值%Calcitonin original clinical value in systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    张志强

    2015-01-01

    Objective To explore the serum calcitonin original value in the diagnosis of systemic inflammatory response syndrome.Methods Select 120 cases of patients with systemic inflammatory response syndrome as the research object, the bacteria infection in 77 cases (group A), the bacterial infection 43 cases (group B), test and compare the two groups of patients the WBC (white blood cell count), hs - CRP (hypersensitive c-reactive protein), PCT (calcitonin former) level.Results A group of patients with PCT were significantly higher than that of group B, statistically significant difference (P 0.05);A组患者的PCT水平显著高于B组,P<0.05,差异具有统计学意义(P<0.05)。患者危重评分与PCT水平呈负相关(r=-0.798,P<0.05)。结论:在全身炎症反应综合征的病原学诊断中,PCT的诊断价值优于中心粒细胞占比、WBC、hs-CRP,是敏感性较高的一种血清学标志,具有重要的临床应用价值。

  9. Peptide Antibiotics for ESKAPE Pathogens

    DEFF Research Database (Denmark)

    Thomsen, Thomas Thyge

    is considered poor compared to medicines for lifestyle diseases. According to the WHO we could be moving towards a post-antibiotic era in which previously treatable infections become fatal. Of special importance are multidrug resistant bacteria from the ESKAPE group (Enterococcus faecium, Staphylococcus aureus...... a cecropin-mellitin hybrid peptide and proved effective in killing colistin resistant Gram-negative A. baumannii in vitro. The molecule was improved with regard to toxicity, as measured by hemolytic ability. Further, this peptide is capable of specifically killing non-growing cells of colistin resistant A...

  10. Peptides and the new endocrinology

    Science.gov (United States)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  11. Novel Formulations for Antimicrobial Peptides

    Directory of Open Access Journals (Sweden)

    Ana Maria Carmona-Ribeiro

    2014-10-01

    Full Text Available Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  12. An enhancer peptide for membrane-disrupting antimicrobial peptides

    Directory of Open Access Journals (Sweden)

    Zhang Hong

    2010-02-01

    Full Text Available Abstract Background NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4 by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn. Results In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against Staphylococcus aureus, whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P. Conclusions NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane.

  13. Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells.

    Science.gov (United States)

    Tsukamoto, Manabu; Menuki, Kunitaka; Murai, Teppei; Hatakeyama, Akihisa; Takada, Shinichiro; Furukawa, Kayoko; Sakai, Akinori

    2016-04-01

    This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the

  14. Strategic approaches to optimizing peptide ADME properties.

    Science.gov (United States)

    Di, Li

    2015-01-01

    Development of peptide drugs is challenging but also quite rewarding. Five blockbuster peptide drugs are currently on the market, and six new peptides received first marketing approval as new molecular entities in 2012. Although peptides only represent 2% of the drug market, the market is growing twice as quickly and might soon occupy a larger niche. Natural peptides typically have poor absorption, distribution, metabolism, and excretion (ADME) properties with rapid clearance, short half-life, low permeability, and sometimes low solubility. Strategies have been developed to improve peptide drugability through enhancing permeability, reducing proteolysis and renal clearance, and prolonging half-life. In vivo, in vitro, and in silico tools are available to evaluate ADME properties of peptides, and structural modification strategies are in place to improve peptide developability. PMID:25366889

  15. Histidine-Containing Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2000-01-01

    Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

  16. Lipoxygenase inhibitor peptides and their use

    OpenAIRE

    Schurink, M.; Boeriu, C.G.; Berkel, van, A.M.; Wichers, H J

    2006-01-01

    The present invention is in the field of enzyme inhibition. In particular it relates to peptide inhibitors for lipoxygenases. The lipoxygenase peptide inhibitors of have the potential to be used as therapeutic drugs as well as food preservatives.

  17. Natriuretic peptides in cardiometabolic regulation and disease

    DEFF Research Database (Denmark)

    Zois, Nora Elisabeth; Bartels, Emil Daniel; Hunter, Ingrid;

    2014-01-01

    decade. Dysregulation of the natriuretic peptide system has been associated with obesity, glucose intolerance, type 2 diabetes mellitus, and essential hypertension. Moreover, the natriuretic peptides have been implicated in the protection against atherosclerosis, thrombosis, and myocardial ischaemia. All...

  18. Gene Related to Anergy in Lymphocytes (GRAIL) Expression in CD4+ T Cells Impairs Actin Cytoskeletal Organization during T Cell/Antigen-presenting Cell Interactions*

    OpenAIRE

    Schartner, Jill M.; Simonson, William T; Wernimont, Sarah A.; Nettenstrom, Lauren M.; Huttenlocher, Anna; Seroogy, Christine M.

    2009-01-01

    GRAIL (gene related to anergy in lymphocytes), is an E3 ubiquitin ligase with increased expression in anergic CD4+ T cells. The expression of GRAIL has been shown to be both necessary and sufficient for the induction of T cell (T) anergy. To date, several subsets of anergic T cells have demonstrated altered interactions with antigen-presenting cells (APC) and perturbed TCR-mediated signaling. The role of GRAIL in mediating these aspects of T cell anergy remains unclear. We used flow cytometry...

  19. GRAIL (Gene Related to Anergy in Lymphocytes) Regulates Cytoskeletal Reorganization through Ubiquitination and Degradation of Arp2/3 Subunit 5 and Coronin 1A*

    OpenAIRE

    Ichikawa, Daiju; Mizuno, Miho; Yamamura, Takashi; Miyake, Sachiko

    2011-01-01

    Anergy is an important mechanism for the maintenance of peripheral tolerance and avoidance of autoimmunity. The up-regulation of E3 ubiqitin ligases, including GRAIL (gene related to anergy in lymphocytes), is a key event in the induction and preservation of anergy in T cells. However, the mechanisms of GRAIL-mediated anergy induction are still not completely understood. We examined which proteins serve as substrates for GRAIL in anergic T cells. Arp2/3-5 (actin-related protein 2/3 subunit 5)...

  20. Purification, structure and function of bioactive peptides

    OpenAIRE

    Eriste, Elo

    2004-01-01

    Peptides are vitally important molecules and many evoke cellular responses. The completion of several genome sequencing projects has revealed a number of new genes. However, as functional peptides often contain posttranslational modifications and/or occur at various lengths, it is of great importance to detect, purify and characterize novel bioactive peptides. To achieve these goals, new methods for peptide detection, isolation and functional characterization have to be d...

  1. Development and use of engineered peptide deformylase in chemoenzymatic peptide synthesis

    NARCIS (Netherlands)

    Di Toma, Claudia

    2012-01-01

    Deze thesis beschrijft het onderzoek naar potentieel van het gebruik van het peptide deformylase (PDF) in chemo enzymatische peptide synthese. PDF is geschikt voor selective N terminale deformylatie van bepaalde N-formyl-peptides zonder gelijktijdige hydrolyse van de peptide binding. Door de uitdagi

  2. Interpreting peptide mass spectra by VEMS

    DEFF Research Database (Denmark)

    Mathiesen, Rune; Lundsgaard, M.; Welinder, Karen G.;

    2003-01-01

    of peptide MS/MS spectra imported in text file format. Peaks are annotated, the monoisotopic peaks retained, and the b-and y-ion series identified in an interactive manner. The called peptide sequence is searched against a local protein database for sequence identity and peptide mass. The report compares...

  3. Synthetic Procedures for Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2004-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  4. Characterization of synthetic peptides by mass spectrometry

    DEFF Research Database (Denmark)

    Prabhala, Bala Krishna; Mirza, Osman Asghar; Højrup, Peter;

    2015-01-01

    Mass spectrometry (MS) is well suited for analysis of the identity and purity of synthetic peptides. The sequence of a synthetic peptide is most often known, so the analysis is mainly used to confirm the identity and purity of the peptide. Here, simple procedures are described for MALDI-TOF-MS an...

  5. Double-Stranded Peptide Nucleic Acids

    DEFF Research Database (Denmark)

    2001-01-01

    A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

  6. Peptides and metallic nanoparticles for biomedical applications.

    NARCIS (Netherlands)

    Kogan, M.J.; Olmedo, I.; Hosta, L.; Guerrero, A.R.; Cruz Ricondo, L.J.; Albericio, F.

    2007-01-01

    In this review, we describe the contribution of peptides to the biomedical applications of metallic nanoparticles. We also discuss strategies for the preparation of peptide-nanoparticle conjugates and the synthesis of the peptides and metallic nanoparticles. An overview of the techniques used for th

  7. Diversity of wheat anti-microbial peptides.

    Science.gov (United States)

    Egorov, Tsezi A; Odintsova, Tatyana I; Pukhalsky, Vitaliy A; Grishin, Eugene V

    2005-11-01

    From seeds of Triticum kiharae Dorof. et Migusch., 24 novel anti-microbial peptides were isolated and characterized by a combination of three-step HPLC (affinity, size-exclusion and reversed-phase) with matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and Edman degradation. Based on sequence similarity and cysteine motifs, partially sequenced peptides were assigned to 7 families: defensins, thionins, lipid-transfer proteins, hevein-like peptides, knottin-like peptides, glycine-rich peptides, and MBP-1 homologs. A novel subfamily of defensins consisting of 6 peptides and a new family of glycine-rich (8 peptides with different repeat motifs) were identified. Three 6-cysteine knottin-like peptides represented by N- and C-terminally truncated variants revealed no sequence homology to any known plant anti-microbial peptides. A new 8-cysteine hevein-like peptide and three 4-cysteine peptides homologous to MBP-1 from maize were isolated. This is the first communication on the occurrence of nearly all families of plant anti-microbial peptides in a single species. PMID:16269343

  8. Toxins and antimicrobial peptides: interactions with membranes

    Science.gov (United States)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  9. Bioactive peptides in dairy products

    Directory of Open Access Journals (Sweden)

    Donata Marletta

    2010-01-01

    Full Text Available Bioactive peptides are specific protein fragments that have a positive impact on body functions and conditions and may ultimately influence health. Most of the biological activities are encrypted within the primary sequence of the native protein and can be released by enzymatic hydrolysis and proteolysis or by food processing. Milk is a rich source of bioactive peptides which may contribute to regulate the nervous, gastrointestinal and cardiovascular systems as well as the immune system, confirming the added value of dairy products that, in certain cases, can be considered functional foods. The main biological activities of these peptides and their bioavailability in dairy products are reviewed. The natural concentration of these biomolecules is quite low and, to date one of the main goals has been to realize products enriched with bioactive peptides that have beneficial effects on human health and proven safety. Even though several health-enhancing products have already been launched and their integration in the diet could help in the prevention of chronic diseases such as hypertension, cancer and osteoporosis, more clinical trials are required in order to develop a deeper understanding of the activity of biopeptides on the human physiological mechanisms and also to assess the efficacy of their effects in a long term view. New scientific data are also needed to support their commercialisation in compliance with current regulations.

  10. Novel and Convenient Method for the Preparation of Phosphonate Peptides and Phosphonamidate Peptides

    Institute of Scientific and Technical Information of China (English)

    XU Jia-Xi; FU Nan-Yan; GAO Yuan-He; ZHNAG Qi-Han; DUAN Li-Fang

    2003-01-01

    @@ Phosphonate and phosphonamidate peptides are phosphorus analogues of natural peptides. They have been great used as stable mimetics of tetrahedral transition states as enzyme inhibitors and as haptens for catalytic antibody research in recent years. Although several methods are available for the preparation of phosphonate peptides and phosphonamidate peptides, all of them use phosphonic acid derivatives as starting materials. The overall yields from the synthesis of phosphonic acid derivatives to desired peptides are not satisfactory in most cases.

  11. Variation in genes related to obesity, weight and weight change and risk of contralateral breast cancer in the WECARE Study population

    Science.gov (United States)

    Brooks, Jennifer D.; Bernstein, Leslie; Teraoka, Sharon N.; Knight, Julia A.; Mellemkjær, Lene; John, Esther M.; Malone, Kathleen E.; Reiner, Anne S.; Lynch, Charles F.; Concannon, Patrick; Haile, Robert W.; Bernstein, Jonine L

    2012-01-01

    Background Body mass index (BMI), a known breast cancer risk factor, could influence breast risk through mechanistic pathways related to sex hormones, insulin resistance, chronic inflammation and altered levels of adipose derived hormones. Results from studies of the relationship between BMI and second primary breast cancer have been mixed. To explore the relationship between BMI and asynchronous contralateral breast cancer (CBC), we examined whether variants in genes related to obesity, weight and weight change are associated with CBC risk. Methods Variants in twenty genes (182 single nucleotide polymorphisms) involved in adipose tissue metabolism, energy balance, insulin resistance and inflammation, as well as those identified through genome-wide association studies of BMI and type II diabetes were evaluated. We examined the association between variants in these genes and the risk of CBC among Caucasian participants (643 cases with CBC and 1,271 controls with unilateral breast cancer) in the population-based Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study using conditional logistic regression. Results After adjustment for multiple comparisons, no statistically significant associations between any variant and CBC risk were seen. Stratification by menopausal or estrogen receptor status did not alter these findings. Conclusion Among women with early onset disease who survive a first breast cancer diagnosis there was no association between variation in obesity-related genes and risk of CBC. Impact Genetic variants in genes related to obesity are not likely to strongly influence subsequent risk of developing a second primary breast cancer. PMID:23033454

  12. Fabrication of Odor Sensor Using Peptide

    Science.gov (United States)

    Hotokebuchi, Yuta; Hayashi, Kenshi; Toko, Kiyoshi; Chen, Ronggang; Ikezaki, Hidekazu

    We report fabrication of an odor sensor using peptides. Peptides were designed to acquire the specific reception for a target odor molecule. Au surface of the sensor electrode was coated by the designed peptide using the method of self assembled monolayers (SAMs). Functionalized Au surfaces by the peptides were confirmed by ellipsometry and cyclic voltammetry. The odorants of vanillin, phenethyl alcohol and hexanol were discriminated by QCM sensor with the peptide surface. Moreover, we verified specific interaction between amino acid (Trp) and vanillin by fluorescence assay.

  13. Computer-Aided Design of Antimicrobial Peptides

    DEFF Research Database (Denmark)

    Fjell, Christopher D.; Hancock, Robert E.W.; Jenssen, Håvard

    2010-01-01

    chemical parameters with biological activities of the peptide, using statistical methods. In this review we will discuss two different in silico strategies of computer-aided antibacterial peptide design, a linear correlation model build as an extension of traditional principal component analysis (PCA......) and a non-linear artificial neural network model. Studies on structurally diverse peptides, have concluded that the PCA derived model are able to guide the antibacterial peptide design in a meaningful way, however requiring rather a high homology between the peptides in the test-set and the in silico...

  14. Peptide-enhanced oral delivery of therapeutic peptides and proteins

    DEFF Research Database (Denmark)

    Kristensen, Mie; Foged, Camilla; Berthelsen, Jens;

    2013-01-01

    Systemic therapy upon oral delivery of biologics, such as peptide and protein drugs is limited due to their large molecular size, their low enzymatic stability and their inability to cross the intestinal epithelium. Ways to overcome the epithelial barrier include the use of peptide-based excipients...... throughout the gastrointestinal (GI) tract, chemical stability is an inherent challenge when employing amino acid-based excipients for oral delivery, and multiple approaches have been investigated to improve this. The exact mechanisms of transepithelial translocation are discussed, and it is believed...... that CPP-mediated translocation involves transcytosis and/or direct translocation through the epithelial cells; whereas TJMP-mediated translocation is dependent on interaction with transmembrane or peripheral TJ proteins. This review focuses on the CPPs and the TJMPs currently employed as excipients...

  15. Towards the MHC-peptide combinatorics.

    Science.gov (United States)

    Kangueane, P; Sakharkar, M K; Kolatkar, P R; Ren, E C

    2001-05-01

    The exponentially increased sequence information on major histocompatibility complex (MHC) alleles points to the existence of a high degree of polymorphism within them. To understand the functional consequences of MHC alleles, 36 nonredundant MHC-peptide complexes in the protein data bank (PDB) were examined. Induced fit molecular recognition patterns such as those in MHC-peptide complexes are governed by numerous rules. The 36 complexes were clustered into 19 subgroups based on allele specificity and peptide length. The subgroups were further analyzed for identifying common features in MHC-peptide binding pattern. The four major observations made during the investigation were: (1) the positional preference of peptide residues defined by percentage burial upon complex formation is shown for all the 19 subgroups and the burial profiles within entries in a given subgroup are found to be similar; (2) in class I specific 8- and 9-mer peptides, the fourth residue is consistently solvent exposed, however this observation is not consistent in class I specific 10-mer peptides; (3) an anchor-shift in positional preference is observed towards the C terminal as the peptide length increases in class II specific peptides; and (4) peptide backbone atoms are proportionately dominant at the MHC-peptide interface.

  16. Natural and synthetic peptides with antifungal activity.

    Science.gov (United States)

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections. PMID:27502155

  17. Flourescent Peptide-Stabilized Silver-Nanoclusters

    DEFF Research Database (Denmark)

    Gregersen, Simon

    for instance small molecules, DNA oligomers, and proteins. Peptides are an intriguing class of biomolecular ligands, due to the large combinatorial space these provide. Furthermore, as peptides have a propensity to fold up into well-defined and somewhat rigid secondary structures, they may serve as excellent...... throughput dramatically with regards to discovery of novel ligands. Our approach employs Fmoc solid-phase peptide synthesis on a PEGA resin which allows for on-resin screening of peptide ligands which, in turn, removes the tedious and labor-intensive work-up of synthesized peptides. The method allows for on......-resin formation of peptide-stabilized Ag-NCs in a reversible manner, which makes identification of novel lead compound from combinatorial peptide libraries possible with a few simple steps. This resulted in the discovery of at least one promising candidate (P262) showing brighter emission, spectral homogeneity...

  18. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions

    DEFF Research Database (Denmark)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco;

    2016-01-01

    . In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited...... for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions...... determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide...

  19. Encapsulation of bioactive whey peptides in soy lecithin-derived nanoliposomes: Influence of peptide molecular weight.

    Science.gov (United States)

    Mohan, Aishwarya; McClements, David Julian; Udenigwe, Chibuike C

    2016-12-15

    Encapsulation of peptides can be used to enhance their stability, delivery and bioavailability. This study focused on the effect of the molecular weight range of whey peptides on their encapsulation within soy lecithin-derived nanoliposomes. Peptide molecular weight did not have a major impact on encapsulation efficiency or liposome size. However, it influenced peptide distribution amongst the surface, core, and bilayer regions of the liposomes, as determined by electrical charge (ζ-potential) and FTIR analysis. The liposome ζ-potential depended on peptide molecular weight, suggesting that the peptide charged groups were in different locations relative to the liposome surfaces. FTIR analysis indicated that the least hydrophobic peptide fractions interacted more strongly with choline on the liposome surfaces. The results suggested that the peptides were unequally distributed within the liposomes, even at the same encapsulation efficiency. These findings are important for designing delivery systems for commercial production of encapsulated peptides with improved functional attributes. PMID:27451165

  20. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions.

    Science.gov (United States)

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco; Østergaard, Jesper

    2016-10-10

    Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations.

  1. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  2. Antimicrobial peptides in human sepsis

    Directory of Open Access Journals (Sweden)

    Lukas eMartin

    2015-08-01

    Full Text Available Nearly 100 years ago, antimicrobial peptides (AMPs were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP 1-3 and human beta-defensins (HBDs 1-3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP -1-3 and HBD-2 in sepsis. The bactericidal/permeability increasing protein (BPI attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP-1-3, lactoferrin, BPI and heparin-binding protein (HBP are increased in sepsis. Human lactoferrin peptide 1-11 (hLF 1-11 possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin (talactoferrin alpha, TLF has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide (LPS. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe

  3. Antimicrobial Peptides: Versatile Biological Properties

    Directory of Open Access Journals (Sweden)

    Muthuirulan Pushpanathan

    2013-01-01

    Full Text Available Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries.

  4. Antihypertensive Peptides from Milk Proteins

    Directory of Open Access Journals (Sweden)

    Heikki Vapaatalo

    2010-01-01

    Full Text Available Dietary proteins possess a wide range of nutritional and functional properties. They are used as a source of energy and amino acids, which are needed for growth and development. Many dietary proteins, especially milk proteins, contain physiologically active peptides encrypted in the protein sequence. These peptides may be released during gastrointestinal digestion or food processing and once liberated, cause different physiological functions. Milk-derived bioactive peptides are shown to have antihypertensive, antimicrobial, immunomodulatory, antioxidative and mineral-binding properties. During the fermentation of milk with certain lactobacilli, two interesting tripeptides Ile-Pro-Pro and Val-Pro-Pro are released from casein to the final product. These lactotripeptides have attenuated the development of hypertension in several animal models and lowered blood pressure in clinical studies. They inhibit ACE in vitro at micromolar concentrations, protect endothelial function in vitro and reduce arterial stiffness in humans. Thus, milk as a traditional food product can after certain processing serve as a functional food and carry specific health-promoting effects, providing an option to control blood pressure.

  5. Chemical Methods for Peptide and Protein Production

    Directory of Open Access Journals (Sweden)

    Istvan Toth

    2013-04-01

    Full Text Available Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported a-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

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

    Science.gov (United States)

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

    2016-10-01

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

  7. Genetic polymorphisms located in genes related to immune and inflammatory processes are associated with end-stage renal disease: a preliminary study

    Directory of Open Access Journals (Sweden)

    Jimenez-Sousa Ma

    2012-07-01

    Full Text Available Abstract Background Chronic kidney disease progression has been linked to pro-inflammatory cytokines and markers of inflammation. These markers are also elevated in end-stage renal disease (ESRD, which constitutes a serious public health problem. Objective To investigate whether single nucleotide polymorphisms (SNPs located in genes related to immune and inflammatory processes, could be associated with ESRD development. Design and methods A retrospective case-control study was carried out on 276 patients with ESRD and 288 control subjects. Forty-eight SNPs were genotyped via SNPlex platform. Logistic regression was used to assess the relationship between each sigle polymorphism and the development of ESRD. Results Four polymorphisms showed association with ESRD: rs1801275 in the interleukin 4 receptor (IL4R gene (OR: 0.66 (95%CI = 0.46-0.95; p = 0.025; overdominant model, rs4586 in chemokine (C-C motif ligand 2 (CCL2 gene (OR: 0.70 (95%CI = 0.54-0.90; p = 0.005; additive model, rs301640 located in an intergenic binding site for signal transducer and activator of transcription 4 (STAT4 (OR: 1.82 (95%CI = 1.17-2.83; p = 0.006; additive model and rs7830 in the nitric oxide synthase 3 (NOS3 gene (OR: 1.31 (95%CI = 1.01-1.71; p = 0.043; additive model. After adjusting for multiple testing, results lost significance. Conclusion Our preliminary data suggest that four genetic polymorphisms located in genes related to inflammation and immune processes could help to predict the risk of developing ESRD.

  8. Human Antimicrobial Peptides and Proteins

    Directory of Open Access Journals (Sweden)

    Guangshun Wang

    2014-05-01

    Full Text Available As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32 can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized

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

    Directory of Open Access Journals (Sweden)

    Jerzy Sowinski

    2011-07-01

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

  10. Molecular imaging probes derived from natural peptides.

    Science.gov (United States)

    Charron, C L; Hickey, J L; Nsiama, T K; Cruickshank, D R; Turnbull, W L; Luyt, L G

    2016-06-01

    Covering: up to the end of 2015.Peptides are naturally occurring compounds that play an important role in all living systems and are responsible for a range of essential functions. Peptide receptors have been implicated in disease states such as oncology, metabolic disorders and cardiovascular disease. Therefore, natural peptides have been exploited as diagnostic and therapeutic agents due to the unique target specificity for their endogenous receptors. This review discusses a variety of natural peptides highlighting their discovery, endogenous receptors, as well as their derivatization to create molecular imaging agents, with an emphasis on the design of radiolabelled peptides. This review also highlights methods for discovering new and novel peptides when knowledge of specific targets and endogenous ligands are not available. PMID:26911790

  11. Use of Galerina marginata genes and proteins for peptide production

    Energy Technology Data Exchange (ETDEWEB)

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  12. Antimicrobial Peptides in Toroidal and Cylindrical Pores

    OpenAIRE

    Mihajlovic, Maja; Lazaridis, Themis

    2010-01-01

    Antimicrobial peptides (AMPs) are small, usually cationic peptides, which permeabilize biological membranes. Their mechanism of action is still not well understood. Here we investigate the preference of alamethicin and melittin for pores of different shapes, using molecular dynamics (MD) simulations of the peptides in pre-formed toroidal and cylindrical pores. When an alamethicin hexamer is initially embedded in a cylindrical pore, at the end of the simulation the pore remains cylindrical or ...

  13. Interaction of small peptides with lipid bilayers.

    OpenAIRE

    Damodaran, K. V.; Merz, K M; Gaber, B P

    1995-01-01

    Molecular dynamics simulations of the tripeptide Ala-Phe-Ala-O-tert-butyl interacting with dimyristoylphosphatidylcholine lipid bilayers have been carried out. The lipid and aqueous environments of the peptide, the alkyl chain order, and the lipid and peptide dynamics have been investigated with use of density profiles, radial distribution functions, alkyl chain order parameter profiles, and time correlation functions. It appears that the alkyl chain region accommodates the peptides in the bi...

  14. Self-assembly of tetraphenylalanine peptides

    OpenAIRE

    Mayans Tayadella, Enric; Ballano Ballano, María Gema; Casanovas Salas, Jordi; Díaz Andrade, Angélica María; Pérez Madrigal, Maria del Mar; Estrany Coda, Francesc; Puiggalí Bellalta, Jordi; Cativiela Marín, Carlos A.; Alemán Llansó, Carlos

    2015-01-01

    Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists o...

  15. Salt-resistant short antimicrobial peptides.

    Science.gov (United States)

    Mohanram, Harini; Bhattacharjya, Surajit

    2016-05-01

    Antimicrobial peptides (AMPs) are promising leads for the development of antibiotics against drug resistant bacterial pathogens. However, in vivo applications of AMPs remain obscure due to salt and serum mediated inactivation. The high cost of chemical synthesis of AMPs also impedes potential clinical application. Consequently, short AMPs resistant toward salt and serum inactivation are desirable for the development of peptide antibiotics. In this work, we designed a 12-residue amphipathic helical peptide RR12 (R-R-L-I-R-L-I-L-R-L-L-R-amide) and two Trp containing analogs of RR12 namely RR12Wpolar (R-R-L-I-W-L-I-L-R-L-L-R-amide), and RR12Whydro (R-R-L-I-R-L-W-L-R-L-L-R-amide). Designed peptides demonstrated potent antibacterial activity; MIC ranging from 2 to 8 μM, in the presence of sodium chloride (150 mM and 300 mM). Antibacterial activity of these peptides was also detected in the presence of human serum. Designed peptides, in particular RR12 and RR12Whydro, were only poorly hemolytic. As a mode of action; these peptides demonstrated efficient permeabilization of bacterial cell membrane and lysis of cell structure. We further investigated interactions of the designed peptides with lipopolysaccharide (LPS), the major component of the outer membrane permeability barrier of Gram-negative bacteria. Designed peptides adopted helical conformations in complex with LPS. Binding of peptides with LPS has yielded dissociation the aggregated structures of LPS. Collectively, these designed peptides hold ability to be developed for salt-resistant antimicrobial compounds. Most importantly, current work provides insights for designing salt-resistant antimicrobial peptides. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 345-356, 2016. PMID:26849911

  16. Genome-based peptide fingerprint scanning

    OpenAIRE

    Giddings, Michael C.; Shah, Atul A.; Gesteland, Ray; Moore, Barry

    2002-01-01

    We have implemented a method that identifies the genomic origins of sample proteins by scanning their peptide-mass fingerprint against the theoretical translation and proteolytic digest of an entire genome. Unlike previously reported techniques, this method requires no predefined ORF or protein annotations. Fixed-size windows along the genome sequence are scored by an equation accounting for the number of matching peptides, the number of missed enzymatic cleavages in each peptide, the number ...

  17. The Function and Development of Soybean Peptides

    Institute of Scientific and Technical Information of China (English)

    Yang Caiyan; Song Junmei

    2009-01-01

    Soybean peptides are small molecules hydrolyzed soy protein,from three to six amino acid composition of the peptide mixture,in 1000Da molecular weight below.Because it has a lot of good physical and chemical properties and physiological functions,in many areas has been widely used.This paper reviews the soybean peptide physical and chemical characteristics,physiological functions,technology and applications in the food industry.

  18. Insect inducible antimicrobial peptides and their applications.

    Science.gov (United States)

    Ezzati-Tabrizi, Reyhaneh; Farrokhi, Naser; Talaei-Hassanloui, Reza; Alavi, Seyed Mehdi; Hosseininaveh, Vahid

    2013-12-01

    Antimicrobial peptides (AMPs) are found as important components of the innate immune system (host defense) of all invertebrates. These peptides can be constitutively expressed or induced in response to microbial infections. Indeed, they vary in their amino acid sequences, potency and antimicrobial activity spectra. The smaller AMPs act greatly by disrupting the structure or function of microbial cell membranes. Here, the insect innate immune system with emphasis on inducible antimicrobial peptide properties against microbial invaders has been discussed.

  19. Modulation of autoimmunity with artificial peptides

    Science.gov (United States)

    La Cava, Antonio

    2010-01-01

    The loss of immune tolerance to self antigens leads to the development of autoimmune responses. Since self antigens are often multiple and/or their sequences may not be known, one approach to restore immune tolerance uses synthetic artificial peptides that interfere or compete with self peptides in the networks of cellular interactions that drive the autoimmune process. This review describes the rationale behind the use of artificial peptides in autoimmunity and their mechanisms of action. Examples of use of artificial peptides in preclinical studies and in the management of human autoimmune diseases are provided. PMID:20807590

  20. A cyclic peptidic serine protease inhibitor

    DEFF Research Database (Denmark)

    Zhao, Baoyu; Xu, Peng; Jiang, Longguang;

    2014-01-01

    Peptides are attracting increasing interest as protease inhibitors. Here, we demonstrate a new inhibitory mechanism and a new type of exosite interactions for a phage-displayed peptide library-derived competitive inhibitor, mupain-1 (CPAYSRYLDC), of the serine protease murine urokinase...... pocket, its carbonyl group aligning improperly relative to Ser195 and the oxyanion hole, explaining why the peptide is an inhibitor rather than a substrate. Substitution of the P1 Arg with novel unnatural Arg analogues with aliphatic or aromatic ring structures led to an increased affinity, depending...... of this peptidic inhibitor, a concept different from conventional attempts at improving inhibitor affinity by reducing the entropic burden....

  1. Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis

    Directory of Open Access Journals (Sweden)

    Takanori Kanazawa

    2015-09-01

    Full Text Available The small interfering RNA (siRNA is suggested to offer a novel means of treating atopic dermatitis (AD because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC, which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA.

  2. Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis.

    Science.gov (United States)

    Kanazawa, Takanori; Shizawa, Yuki; Takeuchi, Mayu; Tamano, Kuniko; Ibaraki, Hisako; Seta, Yasuo; Takashima, Yuki; Okada, Hiroaki

    2015-01-01

    The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA siRNA and functional peptides and determined the intradermal permeation and the anti-AD effects in an AD mouse model. We selected the silk protein, sericin (SC), which is a versatile biocompatible biomaterial to prepare hydrogel as an aqueous gel base. We found that the siRNA was more widely delivered to the site of application in AD-induced ear skin of mice after topical application via the hydrogel containing functional peptides than via the preparation without functional peptides. In addition, the ear thickness and clinical skin severity of the AD-induced mice treated with hydrogel containing anti-RelA siRNA with functional peptides improved more than that of mice treated with the preparation formulated with negative siRNA. PMID:26371030

  3. Synthetic peptide vaccines: palmitoylation of peptide antigens by a thioester bond increases immunogenicity

    DEFF Research Database (Denmark)

    Beekman, N.J.C.M.; Schaaper, W.M.M.; Tesser, G.I.;

    1997-01-01

    or an amide bond. It was found that these S-palmitoylated peptides were much more immunogenic than N-palmitoylated peptides and at least similar to KLH-conjugated peptides with respect to appearance and magnitude of induced antibodies (canine parvovirus) or immunocastration effect (gonadotropin...

  4. Driving engineering of novel antimicrobial peptides from simulations of peptide-micelle interactions

    DEFF Research Database (Denmark)

    Khandelia, Himanshu; Langham, Allison A; Kaznessis, Yiannis N

    2006-01-01

    peptides and their interaction with membrane mimics. In this article, we discuss the promise and the challenges of widely used models and detail our recent work on peptide-micelle simulations as an attractive alternative to peptide-bilayer simulations. We detail our results with two large structural...

  5. Peptide Nucleic Acids Complexes of Two Peptide Nucleic Acid Strands and One

    DEFF Research Database (Denmark)

    1999-01-01

    Peptide nucleic acids and analogues of peptide nucleic acids are used to form duplex, triplex, and other structures with nucleic acids and to modify nucleic acids. The peptide nucleic acids and analogues thereof also are used to modulate protein activity through, for example, transcription arrest...

  6. Mechanism and kinetics of peptide partitioning into membranes from all-atom simulations of thermostable peptides

    OpenAIRE

    Ulmschneider, Martin B.; Doux, Jacques P F; Killian, J. Antoinette; Smith, Jeremy C.; Ulmschneider, Jakob P.

    2010-01-01

    Partitioning properties of transmembrane (TM) polypeptide segments directly determine membrane protein folding, stability, and function, and their understanding is vital for rational design of membrane active peptides. However, direct determination of water-to-bilayer transfer of TM peptides has proved difficult. Experimentally, sufficiently hydrophobic peptides tend to aggregate, while atomistic computer simulations at physiological temperatures cannot yet reach the long time scales required...

  7. Glucagon-like peptide-1

    DEFF Research Database (Denmark)

    Deacon, C F; Holst, Jens Juul; Carr, R D

    1999-01-01

    Type 2 diabetes mellitus is a metabolic disease resulting in raised blood sugar which, if not satisfactorily controlled, can cause severe and often debilitating complications. Unfortunately, for many patients, the existing therapies do not give adequate control. Glucagon-like peptide-1 (GLP-1) is...... an incretin hormone which has a spectrum of activities which oppose the symptoms of diabetes. Of particular significance is the fact that these actions are glucose-dependent, meaning that the risk of severe hypoglycemia is practically eliminated. The recent elucidation of the key role of dipeptidyl...

  8. Atrial natriuretic peptides in plasma

    DEFF Research Database (Denmark)

    Goetze, Jens P; Holst Hansen, Lasse; Terzic, Dijana;

    2015-01-01

    Measurement of cardiac natriuretic peptides in plasma has gained a diagnostic role in the assessment of heart failure. Plasma measurement is though hampered by the marked instability of the hormones, which has led to the development of analyses that target N-terminal fragments from the prohormone....... These fragments are stable in plasma and represent surrogate markers of the actual natriuretic hormone. Post-translational processing of the precursors, however, is revealing itself to be a complex event with new information still being reported on proteolysis, covalent modifications, and amino acid...

  9. Topical Anti-Nuclear Factor-Kappa B Small Interfering RNA with Functional Peptides Containing Sericin-Based Hydrogel for Atopic Dermatitis

    OpenAIRE

    Takanori Kanazawa; Yuki Shizawa; Mayu Takeuchi; Kuniko Tamano; Hisako Ibaraki; Yasuo Seta; Yuki Takashima; Hiroaki Okada

    2015-01-01

    The small interfering RNA (siRNA) is suggested to offer a novel means of treating atopic dermatitis (AD) because it allows the specific silencing of genes related to AD pathogenesis. In our previous study, we found that siRNA targeted against RelA, an important nuclear factor-kappa B (NF-κB) subdomain, with functional peptides, showed therapeutic effects in a mouse model of AD. In the present study, to develop a topical skin application against AD, we prepared a hydrogel containing anti-RelA...

  10. Impacts on the Contents of Brain-Gut Peptides(GAS,NPY and CGRP)in Colonic Mucosa of Depression Model Rats Treated with Different Electroacupuncture%不同电针对抑郁模型大鼠结肠黏膜脑肠肽GAS、NPY、CGRP含量的影响

    Institute of Scientific and Technical Information of China (English)

    滕金艳; 李志刚; 白妍; 赛音朝克图

    2013-01-01

    目的 观察不同电针"百会""印堂"对抑郁模型大鼠结肠黏膜三种胃肠道相关脑肠肽胃泌素(GAS)、神经肽Y(NPY)及降钙素基因相关肽(CGRP)的影响,为揭示针刺治疗抑郁症胃肠道躯体化症状作用途径提供实验依据,并比较不同电针的作用效果.方法 将60只健康SD大鼠随机分为空白组、模型组、百优解组、脉冲电针组、音乐电针组,每组12只.采用慢性不可预见的温和刺激结合孤养方法制备抑郁模型.百忧解组每天将百忧解以生理盐水配制灌胃给药.脉冲电针组针刺大鼠"百会"和"印堂"穴,接脉冲电针治疗仪.音乐电针组取穴同脉冲点针组,接音乐电针治疗仪.采用放射免疫法测定各组大鼠结肠黏膜GAS、NPY、CGRP含量.结果 模型组与空白组相比,大鼠结肠黏膜GAS含量显著降低(P<0.05),NPY含量显著升高(P<0.05),CGRP含量极显著升高(P<0.01);脉冲电针组、音乐电针组及百忧解组与模型组相比,大鼠结肠黏膜GAS含量显著升高(P<0.05或P<0.01),NPY含量显著降低(P<0.05或P<0.01),CGRP含量显著降低(P<0.05或P<0.01);音乐电针组与脉冲电针组相比,大鼠结肠黏膜CGRP含量降低水平更为显著(P<0.05).结论 电针治疗可通过调整抑郁后胃肠道兴奋性激素与抑制性激素的失平衡来影响肠道中脑肠肽含量,从而调控脑-肠轴,使抑郁后胃肠功能紊乱状态得到改善,而且音乐电针组优于脉冲电针组.%Objective To observe the impacts on three gastrointestinal tract related brain — gut pep-tides , named gastrin( GAS ), nenropeptide Y( NPY ) and calcitonin gene related peptide( CGRP ) in colonic mucosa treated with electroacupimctnre( EA )at Baihni( GV20 Jand Yintang( Extra Jin depression model rats so as to discover the experimental evidences for acupuncture effective approach in the treatment of gastrointestinal somatization symptoms of depression and make the comparison of the effects

  11. Regulatory peptides modulate ICAM-1 gene expression and NF-κB activity in bronchial epithelial cells%肺内调节肽对支气管上皮细胞ICAM-1表达及NF-κB活性的调控

    Institute of Scientific and Technical Information of China (English)

    谭宇蓉; 秦晓群; 管茶香; 张长青; 罗自强; 孙秀泓

    2003-01-01

    vasoactive intestinal peptide (VIP) and epidermal growth factor (EGF) decreased ICAM-1 expression in O3-stressed BECs, while endothelin-1 (ET-1) and calcitonin gene-related peptides (CGRP) increased ICAM-1 expression in resting BECs. MG-132 blocked ICAM-1 expression induced by O3, ET-1 and CGRP. The results obtained by using EMSA confirmed that VIP and EGF restrained the activation of NF-ΚB in O3-stressed BECs; CGRP and ET-1 promoted activation of NF-ΚB. These observations indicate that VIP and EGF abated the injury by means of down-regulatory effects on ICAM-1 transcription and NF-ΚB activation, while ET-1 and CGRP enhanced the inflammation reaction by an up-regulatory effect. It is suggested that a developing and intensive airway inflammation correlates closely with a persistent expression of ICAM-1 and repeated activation of NF-ΚB.

  12. Effect of vitamin E supplementation or alfalfa grazing on fatty acid composition and expression of genes related to lipid metabolism in lambs.

    Science.gov (United States)

    González-Calvo, L; Joy, M; Blanco, M; Dervishi, E; Molino, F; Sarto, P; Ripoll, G; Serrano, M; Calvo, J H

    2015-06-01

    The aim of this study was to investigate the effects of vitamin E (VE) supplementation and alfalfa grazing during fattening on fatty acid composition and mRNA expression of genes related to lipid metabolism in the LM of Rasa Aragonesa light lambs. After weaning, 48 lambs were kept indoors and fed a commercial concentrate and a VE supplemented concentrate (480 mg DL-α-tocopheryl acetate/kg DM) for 0 (control [CON]), 10 (VE10d), 20 (VE20d), and 30 d (VE30d) before slaughtering at 22 to 24 kg. Simultaneously, 8 unweaned lambs grazed in alfalfa (154 mg α-tocopherol/kg DM) paddocks with their dams and supplemented with the commercial concentrate (ALF). Immediately after slaughter, LM was sampled to determine gene expression. After 24 h of cooling at 4°C, LM was extracted to determine intramuscular fat (IMF) content and fatty acid composition. The IMF content did not differ with the dietary treatment ( = 0.212). Unweaned grazing alfalfa lambs had greater concentration of rumenic acid (C18:2 c9,t11; P < 0.001) and lower oleic acid (C18:1 c9; = 0.001) content and PUFA n-6:n-3 ratio (P < 0.001) but similar expression of genes implicated in lipid metabolism compared to the concentrate-fed lambs. Vitamin E supplementation did not modify muscle fatty acid composition; however, it increased the expression of FADS2 and ELOVL6, which are involved in desaturation of long-chain fatty acid and the elongation of SFA and MUFA. The results showed that a short period of VE supplementation, especially 10 (VE10d) and 20 d (VE20d), modified gene expression. Overall, the results showed that VE may be acting as a regulatory factor for transcriptional control of genes related to lipid metabolism in the muscle of Rasa Aragonesa light lambs (22-24 kg live weight and younger than 90 d old). PMID:26115290

  13. Effect of the ratios of unsaturated fatty acids on the expressions of genes related to fat and protein in the bovine mammary epithelial cells.

    Science.gov (United States)

    Sheng, R; Yan, S M; Qi, L Z; Zhao, Y L

    2015-04-01

    The objective of this study was to evaluate the effects of the different ratios of unsaturated fatty acids (UFAs) (oleic acid, linoleic acid, and linolenic acid) on the cell viability and triacylglycerol (TAG) content, as well as the mRNA expression of the genes related to lipid and protein synthesis in bovine mammary epithelial cells (BMECs). Primary cells were isolated from the mammary glands of Holstein dairy cows and were passaged twice. Afterward, the cells were randomly allocated to six treatments, five UFA-treated groups, and one control group. For all of the treatments, the the fetal bovine serum in the culture solution was replaced with fatty acid-free BSA (1 g/L), and the cells were treated with different ratios of oleic, linoleic, and linolenic acids (0.75:4:1, 1.5:10:1, 2:13.3:1, 3:20:1, and 4:26.7:1) for 48 h, which were group 1 to group 5. The control culture solution contained only fatty acid-free BSA without UFAs (0 μM). The results indicated that the cell viability was not affected by adding different ratios of UFAs, but the accumulation of TAG was significantly influenced by supplementing with different ratios of UFAs. Adding different ratios of UFAs suppressed the expression of ACACA and FASN but had the opposite effect on the abundances of FABP3 and CD36 mRNA. The expression levels of PPARG, SPEBF1, CSN1S1, and CSN3 mRNA in the BMECs were affected significantly after adding different ratios of UFAs. Our results suggested that groups 1, 2, and 3 (0.75:4:1, 1.5:10:1, and 2:13.3:1) had stronger auxo-action on fat synthesis in the BMECs, where group 3 (2:13.3:1) was the best, followed by group 4 (3:20:1). However, group 5 (4:26.7:1) was the worst. Genes related to protein synthesis in the BMECs were better promoted in groups 2 and 3, and group 3 had the strongest auxo-action, whereas the present study only partly examined the regulation of protein synthesis at the transcriptional level; more studies on translation level are needed in the future

  14. Antimicrobial peptides in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    A Bogaerts

    2010-01-01

    Full Text Available The nematode Caenorhabditis elegans is one of the most successful model species for experimental research because of its sequenced genome, the versatile genetic toolkit and the straightforward breeding among others. In natural conditions however, this tiny worm is constantly surrounded by micro-organisms, simultaneously a source of indispensable nutrition and inevitable pathogens. Lacking an adaptive immune system, the worm solely relies on its innate immune defence to cope with its challenging life style. Hence C. elegans is an excellent model to gain more insight in innate immunity, which is remarkably preserved between invertebrate and vertebrate animals. The innate defence consists of receptors to detect potential pathogens, a complex network of signalling pathways and last but not least, effector molecules to abolish harmful microbes. In this review, we focus on the antimicrobial peptides, a vital subgroup of effector molecules. We summarise the current knowledge of the different families of C. elegans antimicrobial peptides, comprising NLPs, caenacins, ABFs, caenopores, and a recently discovered group with antifungal activity among which thaumatin-like proteins.

  15. Production of peptide antisera specific for mouse and rat proinsulin C-peptide 2

    DEFF Research Database (Denmark)

    Blume, N; Madsen, O D; Kofod, Hans;

    1990-01-01

    not seem to increase the end point titre as tested in direct ELISA. The specificity of the antiserum was determined by competitive ELISA and histochemistry on pancreas sections. Only the synthetic C-peptide 2, but not the homologous synthetic C-peptide 1 from mouse and rat competed efficiently in ELISA...... for antibody binding to the immunizing antigen. Antisera to C-peptide 2, stained islet beta-cells on mouse and rat, but not monkey pancreas sections in immunocytochemical analysis. Preabsorption to the synthetic C-peptide 2, but not the synthetic mouse and rat C-peptide 1 abolished staining. In conclusion we...

  16. Determination of peptide content of DOTA-peptides by metal titration and UPLC

    International Nuclear Information System (INIS)

    Radiolabelled DOTA-peptides are in use for Peptide Receptor Radionuclide Scintigraphy (PRS) and Therapy (PRRT), e.g with 177Lu-DOTA-TATE or 90Y-DOTATOC. Labelling conditions are frequently critical. Therefore, the ingredients of the reaction, e.g. radiometal (90Y and 177Lu) and DOTA-peptide should be pure and the content known. Quality control of DOTA-peptide, can be performed with various methods, most commonly by UV. There are numerous conditions in which this is hampered, e.g. impurities may also have UV-absorption. The aim of the study was to quantify content and purity of DOTA-peptide

  17. Engineered Adhesion Peptides for Improved Silicon Adsorption.

    Science.gov (United States)

    Ramakrishnan, Sathish Kumar; Jebors, Said; Martin, Marta; Cloitre, Thierry; Agarwal, Vivechana; Mehdi, Ahmad; Martinez, Jean; Subra, Gilles; Gergely, Csilla

    2015-11-01

    Engineering peptides that present selective recognition and high affinity for a material is a major challenge for assembly-driven elaboration of complex systems with wide applications in the field of biomaterials, hard-tissue regeneration, and functional materials for therapeutics. Peptide-material interactions are of vital importance in natural processes but less exploited for the design of novel systems for practical applications because of our poor understanding of mechanisms underlying these interactions. Here, we present an approach based on the synthesis of several truncated peptides issued from a silicon-specific peptide recovered via phage display technology. We use the photonic response provided by porous silicon microcavities to evaluate the binding efficiency of 14 different peptide derivatives. We identify and engineer a short peptide sequence (SLVSHMQT), revealing the highest affinity for p(+)-Si. The molecular recognition behavior of the obtained peptide fragment can be revealed through mutations allowing identification of the preferential affinity of certain amino acids toward silicon. These results constitute an advance in both the engineering of peptides that reveal recognition properties for silicon and the understanding of biomolecule-material interactions.

  18. [Application on food preservative of antimicrobial peptides].

    Science.gov (United States)

    Zhao, Hongyan; Mu, Yu; Zhao, Baohua

    2009-07-01

    Antimicrobial peptides are an integral component of the innate immune system, it can counteract outer membrane pathogen such as bacteria, fungi, viruses, protozoan and so on. Owing to the sterilization and innocuity, it has the potential to be crude food preservative. In this paper the uses of antibacterial peptides in the food preservative were analyzed.

  19. Prediction of twin-arginine signal peptides

    DEFF Research Database (Denmark)

    Bendtsen, Jannick Dyrløv; Nielsen, Henrik; Widdick, D.;

    2005-01-01

    peptides and 84% of the annotated cleavage sites of these Tat signal peptides were correctly predicted. This method generates far less false positive predictions on various datasets than using simple pattern matching. Moreover, on the same datasets TatP generates less false positive predictions than...

  20. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies are...