scholarly journals Calcitonin Gene-Related Peptide Influences Bone-Tendon Interface Healing Through Osteogenesis: Investigation in a Rabbit Partial Patellectomy Model

2021 ◽  
Vol 9 (7) ◽  
pp. 232596712110039
Author(s):  
Huabin Chen ◽  
Hongbin Lu ◽  
Jianjun Huang ◽  
Zhanwen Wang ◽  
Yang Chen ◽  
...  
Keyword(s):  
Raman Spectroscopy ◽  
Bone Mineral ◽  
Calcitonin Gene Related Peptide ◽  
Control Group ◽  
Mineral Density ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Partial Patellectomy ◽  
Antagonist Group ◽  
Cgrp Antagonist

Background: Calcitonin gene-related peptide (CGRP), which has been shown to play an important role in osteogenesis during fracture repair, is also widely distributed throughout the tendon and ligament. Few studies have focused on the role of CGRP in repair of the bone-tendon interface (BTI). Purpose: To explore the effect of CGRP expression on BTI healing in a rabbit partial patellectomy model. Study Design: Controlled laboratory study. Methods: A total of 60 mature rabbits were subjected to a partial patellectomy and then randomly assigned to CGRP, CGRP-antagonist, and control groups. In the CGRP-antagonist group, the CGRP receptor antagonist BIBN4096BS was administered to block CGRP receptors. The patella–patellar tendon complex was harvested at 8 and 16 weeks postoperatively and subjected to radiographic, microlaser Raman spectroscopy, histologic, and biomechanical evaluation. Results: Radiographic data showed that local CGRP expression improved the growth parameters of newly formed bone, including area and volumetric bone mineral density ( P < .05 for both). Raman spectroscopy revealed that the relative bone mineral composition increased in the CGRP group compared with in the control group and the CGRP-antagonist group ( P < .05 for both). Histologic testing revealed that the CGRP group demonstrated better integration, characterized by well-developed trabecular bone expansion from the residual patella and marrow cavity formation, at the 8- and 16-week time points. Mechanical testing demonstrated that the failure load, ultimate strength, and stiffness in the CGRP group were significantly higher than those in the control group ( P < .05 for all), whereas these parameters in the CGRP-antagonist group were significantly lower compared with those in the control group at 16 weeks after surgery ( P < .05 for all). Conclusion: Increasing the local concentration of CGRP in the early stages of BTI healing enhanced osteogenesis in a rabbit partial patellectomy model and promoted healing of the BTI injury, whereas treatment using a CGRP antagonist had the opposite effect. However, exogenous CGRP expression did not induce novel bone remolding. Clinical Relevance: CGRP may have potential as a new therapy for BTI injuries or may be added to postoperative regimens to facilitate healing.

scholarly journals Rimegepant: first novel oral calcitonin gene-related peptide inhibitor for migraine

2020 ◽  
Vol 9 (5) ◽  
pp. 829
Author(s):  
Saravana Kumar Ramasubbu ◽  
Senkadhirdasan Dakshinamurthy ◽  
Sarika Palepu ◽  
Arkapal Bandyopadhyay ◽  
Sathish Kumar Rajendran
Keyword(s):  
Area Under The Curve ◽  
Cardiovascular Effects ◽  
Calcitonin Gene Related Peptide ◽  
Causative Role ◽  
Acute Migraine ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Effective Option ◽  
Inflammatory Drugs ◽  
Cgrp Antagonist

Migraine is a neurological condition characterized by intense, debilitating headaches. Symptoms may include nausea, vomiting, numbness or tingling, sensitivity to light and sound. There are multitude of drugs available to treat migraine like triptans, non-steroidal anti-inflammatory drugs, ergots and opioids. But these drugs are associated with adverse effects especially triptans causing cardiovascular effects limiting its use. During last decade, calcitonin gene-related peptide (CGRP) has emerged as a possible mechanism for management of migraine. CGRP has been shown to release during episode of migraine attack and it may play a causative role in induction of migraine. Rimegepant is a novel CGRP antagonist has been approved by FDA for treatment of acute migraine. Rimegepant is a first oral CGRP antagonist compared to other gepants. The oral bioavailability of Rimegepant is 64% and high fat meal can decrease the Cmax, Tmax and area under the curve. This drug is mainly metabolized by CYP3A4 and to lesser extent by CYP2C9. Most common adverse reactions associated with this drug were nausea and urinary tract infection. Clinical trials for Rimegepant have been positive, and results suggest that the drug may be a new safe and effective option for treatment of acute migraine.

scholarly journals Ubrogepant: First Approval

Drugs ◽  
2020 ◽  
Vol 80 (3) ◽  
pp. 323-328 ◽  
Author(s):  
Lesley J. Scott
Keyword(s):  
Small Molecule ◽  
Acute Treatment ◽  
Calcitonin Gene Related Peptide ◽  
Migraine Aura ◽  
Related Peptide ◽  
Global Approval ◽  
Calcitonin Gene ◽  
The Usa ◽  
Cgrp Antagonist

Abstract Ubrogepant (Ubrelvy™) is an orally administered, small molecule, highly-selective, calcitonin gene-related peptide (CGRP) antagonist that was developed by Allergan under license to Merck & Co. as an acute treatment for migraine. In December 2019, ubrogepant received its first global approval in the USA for the acute treatment of migraine (± aura) in adults. This article summarizes the milestones in the development of ubrogepant leading to its first global approval for the acute treatment of migraine (± aura) in adults.

The calcitonin gene-related peptide (CGRP) antagonist CGRP8–37 blocks vasodilatation in inflamed rat skin: involvement of adrenomedullin in addition to CGRP

2001 ◽  
Vol 310 (2-3) ◽  
pp. 169-172 ◽  
Author(s):  
Duc Quyen Chu ◽  
Steve Legon ◽  
David M Smith ◽  
Soraia K.P Costa ◽  
Frank Cuttitta ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Skin Involvement ◽  
Rat Skin ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Antagonist

scholarly journals CALCB rs3829222 T/T Genotype and Low Expression of CALCB Are High-Risk Factors for Adenoid Cystic Carcinoma of Salivary Gland

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Chaobin Dai ◽  
Bin Zhang ◽  
Yunyang Liao ◽  
Qicai Liu ◽  
Feiguang Wu ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Adenoid Cystic Carcinoma ◽  
Normal Control ◽  
Calcitonin Gene Related Peptide ◽  
Normal Control Group ◽  
Control Group ◽  
Salivary Adenoid Cystic Carcinoma ◽  
Related Peptide ◽  
Adenoid Cystic ◽  
Calcitonin Gene

Objectives. To investigate the relationship between polymorphisms of calcitonin-related peptide gene II (beta-calcitonin gene-related peptide (βCGRP), CALCB) and serum CGRP levels in salivary adenoid cystic carcinoma. Materials and Methods. Using the polymerase chain reaction (PCR) technique, the full-length amplification and genotype analysis of CALCB genes were performed in 39 patients with adenoid cystic carcinoma of salivary gland and 158 normal controls. The gene frequencies of major genotype of CALCB in adenoid cystic carcinoma of salivary gland and normal control group were analyzed. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate serum calcitonin gene-related peptide (CGRP) and its concentration of alpha and beta subtypes. Results. Univariate logistic regression analysis showed that the CALCB rs2839222 T/T genotype was closely related to the occurrence of salivary adenoid cystic carcinoma, with a correlation coefficient of 3.89. Conclusions. The serum CGRP concentration in the salivary adenoid cystic carcinoma group was 1.56 times that of the normal control group. The αCGRP subtype was significant, which was 3.02 times that of the normal control. The polymorphism of βCGRP gene is associated with genetic susceptibility to salivary adenoid cystic carcinoma, and serum CGRP and βCGRP can be used as novel markers of salivary adenoid cystic carcinoma.

scholarly journals Comparative evaluation of serum calcitonin gene related peptide level in patients with migraine headache with and without aura

2021 ◽  
Author(s):  
Mostafa Rezaee ◽  
Nahid Ashja zadeh ◽  
Sadegh Izedi ◽  
Farinaz Fakhri
Keyword(s):  
Correlation Coefficient ◽  
Rank Correlation ◽  
Calcitonin Gene Related Peptide ◽  
Clinical Findings ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Serum Calcitonin ◽  
Related Peptide ◽  
Spearman’S Rank Correlation ◽  
Calcitonin Gene

Abstract Background During a migraine attack, trigeminal activation results in the release of calcitonin gene-related peptide (CGRP), which stimulates the release of inflammatory cytokines playing an important role in migraine. We analyze the serum level of CGRP between two groups of migrainous patients (with aura and without aura) Materials and Methods Thirty six migraine patients (included 18 patients with aura and 18 without aura) additionally 18 healthy volunteers consisted control group were selected from the clinic of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran, between March 2020 and November 2020. The CGRP level were determined from the sera of patients with migraine and control subjects by enzyme-linked immunosorbent assay kits. Spearman's rank correlation coefficient was also determined to calculate the correlation between CGRP and clinical findings. Results The level of CGRP in groups were significantly different between groups (P = 0.00). Also, the level of CGRP in aura group were significantly higher than non-aura group (P = 0.045). The Spearman’s correlation coefficient revealed a positive and significant correlation between the CGRP concentration and age (p = 0.042, r = 0.172), BMI (p = 0.013, r = 0.08), VAS (P = 0.006 ,r = 0.09), frequency of attacks (p = 0.005, r = 0.9), duration of each attack (p = 0.016, r = 0.23), Migraine Disability Assessment Scale.(p = 0.00, r = 0.785), average of number of Medication (p = 0.00, r = 0.694). However, no significant correlation was observed with gender. (P > 0.05 ) Conclusions In our study, we found migraine patients had a higher CGRP level than healthy controls and the level of CGRP was related significantly with the duration, BMI, frequency of headache, age, number of headaches per day. In conclusion, our results confirmed that CGRP may be involved in the pathogenesis of migraine attacks and related with the multiple clinical characteristics.

Diagnostic value of migraine biomarker — calcitonin-gene-related peptide

2021 ◽  
Author(s):  
O. Y. Dubenko ◽  
A. G. Chernenko
Keyword(s):  
Serum Level ◽  
Daily Activity ◽  
Episodic Migraine ◽  
Cervicogenic Headache ◽  
Calcitonin Gene Related Peptide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
And Performance

Objective — to study the diagnostic significance of the serum level of calcitonin‑gene‑related peptide as a tool for the differential diagnosis of migraine with comorbid neck pain and tension of the pericranial muscles and cervicogenic headache. Methods and subjects. The study included 112 patients (84 women, 28 men) aged from 18 to 58 years. In 77 patients episodic migraine was diagnosed (with a typical aura in 17 and without aura in 60 patients), in 35 patients suffered from cervicalgia with muscle‑tonic syndromes and cervicogenic headache. Among patients with migraine, 42 had concomitant cervicalgia with muscle‑tonic dysfunction. The examined patients were distributed into 3 clinical groups: I — combination of episodic migraine with cervicalgia, II — episodic migraine, III — cervicalgia without migraine. In all patients, pain intensity was assessed using a visual analogue scale, the effect of migraine on daily activity and performance using the MIDAS and HIT‑6 scales, and the Neck Disability Index. The control group for comparing the serum level of CGRP consisted of 30 clinically healthy persons. The serum level of CGRP was determined by enzyme‑linked immunosorbent assay using the sandwich ELISA principle. Results. In the group of patients with a combination of episodic migraine with cervicalgia and cervicogenic headache, compared with the group with isolated migraine, the number of days with headache over the last 3 months was higher (р < 0.001), the influence of headache on daily activity and performance according to the MIDAS scales and HIT‑6 was more significant (both р < 0.001) and the number of combined analgesics used was higher (р < 0.001). Plasma level of CGRP was statistically significantly higher in patients with episodic migraine compared with the group with cervicalgia without migraine (р < 0.05), where it did not differ from the control. The CGRP level was statistically significantly higher in women with migraine compared to men (р < 0.001), but did not differ in patients with migraine with and without aura (р > 0.05). Conclusions. The serum level of calcitonin‑gene‑related peptide is a reliable diagnostic and differential diagnostic laboratory biomarker of episodic migraine. The presence of concomitant cervicalgia in patients with episodic migraine significantly affects the level of CGRP in the blood plasma and the course of the disease (an increase in the number of days with headache, the amount of analgesic use, decreased performance and daily activity).  

Mild irritant prevents ethanol-induced gastric mucosal microcirculatory disturbances through actions of calcitonin gene-related peptide and PGI2in rats

2004 ◽  
Vol 286 (1) ◽  
pp. G68-G75 ◽  
Author(s):  
Takeo Saeki ◽  
Takashi Ohno ◽  
Kazuhisa Kamata ◽  
Katsuharu Arai ◽  
Sumito Mizuguchi ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Mucosal Injury ◽  
Inhibitory Effect ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Beraprost Sodium ◽  
Calcitonin Gene ◽  
Microcirculatory Disturbances ◽  
Mild Irritant ◽  
Cgrp Antagonist

Pretreatment with a mild irritant such as 1 M NaCl prevented ethanol-induced mucosal injury, which was abolished by indomethacin, suggesting involvement of endogenous PGs. With the use of intravital microscopy, we investigated the mechanism in microcirculation whereby a mild irritant prevents ethanol-induced mucosal injury. Microcirculation of the basal part of gastric mucosa in anesthetized rats was observed through a window with transillumination. Diameters of arterioles, collecting venules, and venules were measured with an electric microscaler. One molar NaCl alone caused dilation of arterioles and constrictions of collecting venules and venules, which were inhibited by indomethacin. Ethanol (50%) applied to mucosa constricted collecting venules and venules but dilated arterioles. Constriction of collecting venules resulted in mucosal congestion. Pretreatment with 1 M NaCl inhibited ethanol-induced constrictions of collecting venules and venules, and administration of indomethacin or a calcitonin gene-related peptide (CGRP) antagonist, CGRP-(8–37), abolished elimination of constrictions. Topical application (1 nM–10 μM) of PGE2or beraprost sodium (a PGI2analog) to microvasculature markedly and dose-dependently dilated arterioles, whereas that of PGE2, but not beraprost, slightly constricted collecting venules. Pretreatment of microvasculature with a nonvasoactive concentration of PGE2(100 nM) or beraprost (1 nM) completely inhibited ethanol-induced constriction of collecting venules. The inhibitory effect of beraprost but not of PGE2was abolished by CGRP-(8–37). Present results suggest that the mechanism whereby 1 M NaCl prevents ethanol-induced injury is elimination of constrictions of collecting venules and venules by CGRP whose release may be enhanced by PGI2but not by PGE2.

scholarly journals New CGRP Antagonists

2001 ◽  
Vol 1 ◽  
pp. 16-16
Author(s):  
H. N. Doods ◽  
M. Schindler
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Cgrp Antagonist

The presentation will focus on BIBN 4096 BS, since this compound is still the only potent calcitonin gene-related peptide (CGRP)-antagonist described so far[1].

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