Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirteen patients with symptoms of active Paget's disease of bone, confirmed biochemically and radiologically, were studied. Each patient received a 6 months' course of therapy with human synthetic calcitonin (HCT), starting with 1 mg daily subcutaneously or intramuscularly for the first month and thereafter 3 times per week for 5 months. Twelve patients completed the course of therapy. Ten of the 12 patients derived moderate to great symptomatic improvement from their treatment. The improvement usually became evident 6 weeks after the start of treatment and this improvement persisted in 4 patients from 6 months to 1 year after treatment was stopped. The plasma alkaline phosphatase had fallen from the initial values by a mean of 26% after 6 weeks and 31% after 6 months of treatment. The urinary hydroxyproline likewise had fallen by 42% at 6 weeks and 46% at 6 months. Side-effects were generally mild and self-limiting, with flushing being the most common. It is concluded that human calcitonin is beneficial in the treatment of Paget's disease of bone and may prevent the problems of antibody resistance and allergic phenomena encountered with other preparations of calcitonin.
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PMID:Paget's disease of bone (osteitis deformans) treated with human synthetic calcitonin. 85 Aug 45

Human calcitonin has proven to be an effective drug in the management of Paget's disease. Bone pain decreased in a high percentage of cases and biochemical indices improved in all but a few instances. Radiologic regression of the disease often was seen after several years of treatment. The drug has been uniformly effective when administered to patients who have develped resistance to porcine or salmon calcitonin due to circulating antibodies. The incidence of side effects, mainly facial flushing and nausea, was variable and uncommonly resulted in discontinuation of treatment. Further studies are required to establish the minimum effective dose.
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PMID:Human calcitonin treatment of Paget's disease of bone. 91 95

A patient is described with a 17-year history of intractable left-sided facial pain. The pain occurred daily in 5 sec spasms to a maximum of one every 2-3 min and was restricted to the left upper face. It was associated with rhinorrhoea on the left and often with ipsilateral facial flushing. Conventional therapy, including carbamazepine, baclofen and three posterior fossa explorations, had not provided lasting relief. Local facial stimulation by tapping a painful trigger point led to both pain and flushing of the face ipsilaterally. During this flushing, blood was collected and assayed using sensitive radioimmunoassays for several neuropeptides (neuropeptide Y, substance P, vasoactive intestinal polypeptide and calcitonin gene-related peptide). A marked (119%) increase in calcitonin gene-related peptide was noted in the external jugular vein blood ipsilaterally during the flushing with no change in the other peptides measured. To quantitate the effect of calcitonin gene-related peptide on human extracranial vessels, standard pharmacological procedures were used to examine the potency of the peptide as a vasodilator of human facial artery. The IC50 of calcitonin gene-related peptide for the prostaglandin F2 alpha-precontracted human facial artery was 10(-9) mol/l. The relevance of these observations to the clinical problem of migraine is considered.
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PMID:Cutaneous sensory stimulation leading to facial flushing and release of calcitonin gene-related peptide. 155 59

A 58-year-old euthyroid man with episodic flushing and a 2-year history of progressive wheezing was found to have a hypoechoic lesion in one lobe of his thyroid and hypercalcitoninemia in response to pentagastrin stimulation. Thyroidectomy revealed bilateral C-cell hyperplasia unexpectedly associated with chronic lymphocytic thyroiditis. The C-cells exhibited positive immunohistochemical staining for calcitonin and polyclonal carcinoembryonic antigen (CEA). Postoperatively, the wheezing and flushing subsided and the serum calcitonin level was not elevated with pentagastrin stimulation. The substance or substances responsible for the wheezing and flushing were not specifically identified. Nine other specimens of chronic lymphocytic thyroiditis were examined for C-cell hyperplasia and two had small hyperplastic foci, but of a lesser degree than the index case. These patients did not exhibit wheezing and flushing. The development of C-cell hyperplasia in chronic lymphocytic thyroiditis is uncommon and the mechanism for its occurrence is unexplained. This patient appears to be the first reported case of symptomatic C-cell hyperplasia associated with chronic lymphocytic thyroiditis. The substance or substances responsible for the clinical symptoms remain to be identified.
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PMID:Symptomatic C-cell hyperplasia associated with chronic lymphocytic thyroiditis. 141 1

The innervation of the cranial vessels by the trigeminal nerve, the trigeminovascular system, has recently been the subject of study in view of its possible role in the mediation of some aspects of migraine. Since stimulation of the trigeminal ganglion in humans leads to facial pain and flushing and associated release of powerful neuropeptide vasodilator substances, their local release into the extracerebral circulation of humans was determined in patients who had either common or classic migraine. Venous blood was sampled from both the external jugular and cubital fossa ipsilateral to the side of headache. Plasma levels of neuropeptide Y, vasoactive intestinal polypeptide, substance P, and calcitonin gene-related peptide were determined using sensitive radioimmunoassays for each peptide, and values for the cubital fossa and external jugular and a control population were compared. A substantial elevation of the calcitonin gene-related peptide level in the external jugular but not the cubital fossa blood was seen in both classic and common migraine. The increase seen in classic migraine was greater than that seen with common migraine. The other peptides measured were unaltered. This finding may have importance in the pathophysiology of migraine.
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PMID:Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. 169 72

Pheochromocytomas may produce several vasoactive peptides. We studied a 39-year-old man who presented with paroxysmal flushing and abdominal pain with normal blood pressure. Laboratory and radiologic studies established the diagnosis of right adrenal pheochromocytoma, and histologic and ultrastructural examination showed the tumor to be a typical pheochromocytoma. Tissue culture yielded large quantities of norepinephrine and epinephrine. However, immunohistochemical studies, tissue assays, and in vitro cultures documented production of several peptides, including calcitonin gene-related peptide and vasoactive intestinal polypeptide in tumor cells. The patient has been asymptomatic after tumor resection. Production of multiple peptides by this tumor may account for the flushing and lack of hypertension, despite elevated catecholamine levels in this patient.
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PMID:Pheochromocytoma producing multiple vasoactive peptides. 173 41

Clinical interest in salmon calcitonin began in 1972 when this peptide was shown to be effective in the treatment of Paget's disease. Salmon calcitonin is more potent than porcine calcitonin, with human calcitonin intermediate in potency. Salmon calcitonin is a highly effective therapeutic agent in the treatment of Paget's disease. During chronic treatment with salmon calcitonin, alkaline phosphatase activity and urinary hydroxyproline excretion decrease on an average of 50% in patients with Paget's disease. Patients may experience a variety of clinical benefits during chronic treatment, including relief of bone pain, a reversal of neurological deficits, stabilization or improvement of hearing loss, and improvement of vascularity of bone. Radiologic healing of osteolytic lesions in particularly striking with calcitonin treatment. Paget's disease patients prefer treatment with salmon calcitonin administered by means of a nasal spray. Salmon calcitonin has an excellent safety profile and produces mild side effects in a small percentage of patients. The most common side effects associated with salmon calcitonin administration are nausea and facial flushing. It is unusual to observe severe side effects. In about 20% of patients, production of antibodies may neutralize the effects of the exogenously administered calcitonin; these patients respond to human calcitonin. At this time salmon calcitonin should still be considered a valuable therapeutic agent in the treatment of Paget's disease, particularly in patients with osteolytic lesions.
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PMID:Clinical efficacy of salmon calcitonin in Paget's disease of bone. 193 17

Calcitonin has been isolated and its structure defined from several species, including man. Synthetic preparations of several calcitonins are available for clinical use. Of these, porcine (pCT), human (hCT), and salmon (sCT) have been synthetized according to their natural sequences, while eel calcitonin (cCT) is available as amino-suberic acid derivative (ASU-eCT). The different molecular configuration results in different biological potency and tolerability. Currently, the potency of calcitonin in man is evaluated by its capacity of lowering serum calcium and stimulating cAMP plasma levels after acute infusion. In normal subjects, cAMP stimulation seems to be a more sensitive test, since plasma calcium in normal subjects is poorly affected by an acute treatment with calcitonin. On the other hand, the side effects are usually assessed by clinical observation, on the basis of duration and intensity of the symptoms. Our experience, emerging from several studies devoted to comparing the biological activity and tolerability of different calcitonin preparations in humans, indicates that the hypocalcemic effect and the increase of plasma cAMP are produced by all peptides, according to the potency order sCT greater than hCT greater than ASU-eCT. For all peptides, the most constant side effect is flushing, and the frequency order of side effects is hCT greater than sCT = ASU-eCT.
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PMID:Biological activity of different calcitonins in men. 217 71

Seventeen patients with malignant hypercalcemia were treated with a combination of a single dose of 3-amino 1-hydroxypropylidene-1-bisphosphonate (APD [also known as AHPrBP or palmidronate disodium]) and salmon calcitonin given as suppositories for 3 days. To assess whether such a combined short treatment has a significant benefit leading to earlier normalization of the plasma calcium level than does APD alone, 17 additional patients matched for the type of tumor, initial plasma calcium level, urinary hydroxyproline level, and the dose of APD served as controls. All patients receiving the combination of calcitonin and APD achieved normalization of the plasma calcium level within 9 days, with a decrease from 3.22 +/- 0.90 mmol/L (mean +/- SEM) to 2.29 +/- 0.03 mmol/L. In the group receiving APD alone, the plasma calcium level normalized in only 14 of 17 patients by day 9. In the group receiving calcitonin and APD, the drop in the plasma calcium level occurred more rapidly, and the plasma calcium values were lower from days 2 to 4. This advantage was explained by the calciuric effect of calcitonin, as reflected by a significant decrease in the notional setting of renal reabsorption of calcium, reaching 2.16 +/- 0.06 mmol/L compared with 2.34 +/- 0.06 mmol/L in the group receiving APD alone. There were no side effects of both treatments, in particular neither flushing nor nausea induced by the suppositories of calcitonin. Clinical Improvement occurred after 2 days in the group receiving the combined treatment. In conclusion, the combined treatment is rapidly effective and safe in the treatment of patients with hypercalcemia, particularly when the notional setting of renal tubular reabsorption of calcium is increased and a rapid correction of the plasma calcium level is needed.
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PMID:Fast and effective treatment of malignant hypercalcemia. Combination of suppositories of calcitonin and a single infusion of 3-amino 1-hydroxypropylidene-1-bisphosphonate. 222 97

We have recently shown that the novel neuropeptide calcitonin gene-related peptide, CGRP, is a potent vasodilator. In this paper we report a detailed study of the effects of CGRP in human skin. CGRP induces a clearly defined, long-lasting erythema. We have measured the effect of CGRP on blood flow in human skin using a laser Doppler technique and have demonstrated increased local blood flow that persists for a number of hours. We compared the response of CGRP with other known vasodilators [histamine, prostaglandin (PG) E2, PGI2, substance P, and vasoactive intestinal peptide (VIP)] in the skin, and in all subjects the erythema induced by CGRP was more persistent than that induced by the other mediators tested. Except at high doses the local vasodilatation induced by CGRP was not associated with a wheal and flare as seen with histamine, substance P, and VIP. CGRP is an extremely potent vasodilator and if released into the circulation, or locally from peripheral nerve endings, it could have a role in the regulation of blood flow in both physiologic and pathologic conditions; CGRP may be the endogenous mediator of the flare in the triple response. A deficiency in CGRP secretion or action could be an important component of peripheral vascular disease. Some flushing reactions (e.g., those associated with medullary thyroid carcinoma) may result from circulating CGRP.
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PMID:Potent vasodilator activity of calcitonin gene-related peptide in human skin. 242 85


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