Plasma Calcitonin Research Articles

Aberrant pain modulation in trigeminal neuralgia patients.

Objectives The present study attempts to understand the role of supraspinal nociceptive pain modulation in typical trigeminal neuralgia (TN) patients by using a conditioned pain modulation paradigm and estimation of plasma levels of two important neuromodulators; Calcitonin Gene-Related Peptide andβ-endorphin. Methods Twenty TN patients and 20 healthy, age and gender-matched subjects participated in the study. The participants' hot pain thresholds (HPT) were measured over their affected side on the face. Testing sites were matched for healthy controls. For the conditioned pain modulation their contralateral foot was immersed in noxious cold (5°C) water bath (conditioning stimuli) for 30s and HPT (testing stimuli) was determined before, during and till 5min after the immersion. Plasma Calcitonin Gene-Related Peptide and β-endorphin levels were estimated to understand their role in disease pathogenesis and pain modulation. Results Change in HPT during foot immersion was significantly higher in healthy controls compared to TN patients (p<0.0001). The changes recorded in HPT in patients, were significant only in 2nd and 3rd minute post immersion. While in healthy controls, the effect lasted till the 4th minute. The concentration of beta-endorphin was significantly lower in TN patients (p=0.003) when compared to healthy controls. Conclusions The results suggest that there is an impairment in supraspinal pain modulation also known as Diffuse Noxious Inhibitory Controls in typical TN and that the reduced levels of β-endorphin may contribute to the chronic pain state experienced by patients.

Neoadjuvant Lenvatinib in Advanced Unresectable Medullary Thyroid Carcinoma: A Case Report

Medullary thyroid carcinoma, a rare form of thyroid cancer, is typically managed with surgical excision. However, in patients with locally-invasive tumors, an aggressive surgical attempt may result in unnecessary morbidity. Neoadjuvant tyrosine kinase inhibition has been utilized to downstage tumors prior to surgical excision but its role in thyroid cancer treatment is not well-established. We describe the potential role that lenvatinib, a tyrosine kinase inhibitor, may have as a neoadjuvant agent in advanced locoregional medullary thyroid carcinoma. Our patient presented with a large left thyroid mass and bulky left lateral neck lymphadenopathy. Imaging studies revealed a hypervascular and locally-invasive tumor with metastatic central and left lateral lymphadenopathy. A lymph node biopsy cytologic evaluation and plasma calcitonin concentration of 32,926 pg/mL were consistent with medullary thyroid carcinoma. Rearranged during transfection germline mutation testing was negative. A multidisciplinary team of physicians deemed the patient a poor surgical candidate and recommended 4 months of neoadjuvant lenvatinib therapy to reduce tumor burden with a subsequent reassessment of resectability. Given the tumor's hypervascularity, lenvatinib was chosen due its potent vascular endothelial growth factor receptor inhibition, as well as its availability at our institution. Lenvatinib therapy resulted in rapid regression of tumor volume (approximately 70% reduction) as documented by computed tomography and ultrasound. Surgery after 4 months of treatment resulted in a 99% reduction in serum calcitonin and imaging studies 6 months later showed no residual disease. Lenvatinib has potential as a neoadjuvant agent in advanced medullary thyroid carcinoma, and permitted tumor resection in this previously inoperable patient.

Development of a system for measuring calcitonin in the stingray Dasyatis akajei (a cartilaginous fish): the possible involvement of stingray calcitonin in gonadal development

To elucidate the physiological role of calcitonin (CT) in stingrays (cartilaginous fish), an enzyme-linked immunosorbent assay (ELISA) system using a specific antibody against stingray CT has been developed. Synthetic stingray CT was subcutaneously injected into mice four times—once every 2 weeks—together with an adjuvant. We purified the IgG antibody fraction using the protein A affinity chromatography from collected antiserum. Evaluating the antibody titer, we found the antibody’s optimum dilution ratio to be 600 times. Competitive ELISA has been developed using the antibody diluted 600 times. Our antibody did not cross-react with teleost CTs and muscle extraction, but cross-reacted with stingray plasma and the extract of the ultimobranchial gland, the secretary organ of stingray CT. Using this ELISA, we measured the plasma CT level in stingrays and examined its correlation with several mineral concentrations. Plasma CT did not show significant correlation to calcium, magnesium, inorganic phosphorus, sodium, chlorine, or urea, although there was a correlation among the factors involved in osmoregulation, such as sodium, chlorine, and urea. On the other hand, plasma CT was significantly correlated to body weight and length. Furthermore, there was a significant correlation between plasma CT and gonad weight. Since plasma CT was correlated with the weight of liver, which is involved in the synthesis of egg yolk protein, we examined the influence of 17β-estradiol (E2) on CT secretion. After E2 injection, the plasma CT level increased significantly. This is the first study to demonstrate that E2 induced plasma CT secretion in cartilaginous fish.

MON-383 Sporadic Bilateral Pheochromocytoma with Renal Pelvis Paraganglioma: A Rare Coexisting Occurrence

Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare neuroendocrine catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla and the extra-adrenal autonomic paraglanglia respectively. The natural course of this disease increases morbidity and mortality. Most cases are sporadic, unicentric and unilateral and occur in the 4th and 5th decade of life. Hereditary disease typically presents at a younger age and are likely to be bilateral and linked to germline genetic mutations. This is the case of a 26 year-old lady with history of early onset high blood pressure (HTN) in the setting of bilateral (B/L) adrenal masses. At 21 years old, she was diagnosed with HTN accompanied with symptoms of depression, cry spells, anxiety, tachycardia and episodes of chest pain that warranted frequent ER visits. She was started on labetalol, lisinopril and hydrochlorothiazide. The work-up for early onset HTN prompted urine fractionated catecholamine collection that revealed normal metanephrines but elevated normetanephrines more than 10 times above the upper limit of normal. SPECT CT abdomen and pelvis showed a 3 cm left adrenal mass lesion compatible with a pheochromocytoma and a 4.5cm complex but dominantly low right adrenal mass with no significant uptake suggestive of a benign adenoma. Dexamethasone suppression test, 24-hour urine free cortisol, aldosterone, plasma renin activity, calcitonin, calcium and PTH levels were within normal limits. Repeated testing showed urine norepinephrine 793 mcg/24h (normal 15-100), urine dopamine 641mcg/24h (normal 52-480), normal urine epinephrine, plasma normetanephrines 2383pg/ml (normal <148) and normal plasma metanephrines. With the diagnosis of Normetanephrine secreting PHEO, She was alpha blocked to undergo left adrenalectomy. Final pathology confirmed left PHEO. After surgery lisinopril was restarted due to HTN, and cathecholamines mildly improved but remained elevated. 7 month later CT abdomen w/wo contrast plus PET CT described status post left adrenalectomy; interval decrease in size of the right adrenal mass now avidly positive reflecting an additional PHEO and an enhancing mass in the left renal pelvis and left renal calyx consistent with a PGL, retrospectively also present in prior imaging. Interestingly no germline mutation was identified in genetic analysis. Simultaneous PGL and PHEO is rare with an incidence of 0.3 and 1 per 100000. Our detailed literature review found only two cases with bilateral PHEO and PGL. Less than 17 cases with renal PGL have been published. Our case is the first sporadic B/L PHEO with renal PGL ever reported. Although no specific genetic mutation was found in our patient, we propose close monitoring with imaging and to be continued in patients with a hereditary pattern. As genetic technology continues to evolve we will be able to identify a clear mutation in this type of patients.

A prospective study of headache and neuropeptides in patients with pituitary adenomas

To evaluate clinical criteria for headache associated with pituitary adenoma (HaPA) in the International Classification of Headache Disorders (ICHD) 3rd edition version criteria and further determine whether elevations of plasma calcitonin gene-related peptide and pituitary adenylate cyclase-activating peptide 1-38 (PACAP1-38) concentration contribute to HaPA. Demographic and clinical features of consecutive patients with pituitary adenoma were recorded. Plasma calcitonin gene-related peptide and PACAP1-38 concentrations in pituitary adenoma patients within 72 h pre- and post-operation were measured. Primary outcome for HaPA patients were 50% reduction of moderate-to-severe headache days at 3 months after discharge. Sixty-three patients with pituitary adenoma were recruited, 33 (52.4%) of whom had headache. The patients who had HaPA presented with migraine-like (32.9%), tension-type-like (12.1%), and stabbing headache (9.1%). Non-functional adenoma was present in the majority of cases (82.5%). Surgical resection improved headache in 83.3% of cases at 3 month follow-up. Pre- and post-operative calcitonin gene-related peptide and PACAP1-38 levels were significantly higher in patients with headache than in those without headache (p < 0.05). Plasma calcitonin gene-related peptide and PACAP1-38 levels at 72 h post-operation were lower at 72 h after operation in patients who had greater improvement in headache compared with those who had little improvement, while plasma calcitonin gene-related peptide and PACAP1-38 levels were similar between these two groups preoperatively. Most pituitary adenoma patients have non-functional adenoma, and half of this group have HaPA, indicating that the ICHD-3 criteria for HaPA with the emphasis on secretion status need further modifications. Lower plasma calcitonin gene-related peptide and PACAP1-38 concentrations at 72 h after operation may predict a better outcome in patients with HaPA.

Effect of otopoint pellet-pressing combined with medication on clinical symptoms of migraine patients and changes of plasma 5-HT and CGRP contents

To investigate the short-term and long-term clinical effects of otopoint pellet-pressing combined with medication in the treatment of patients with migraine without aura and its impact on plasma 5-hydroxytryptamine(5-HT) and calcitonin gene-related peptide(CGRP) contents. Patients with migraine without aura were randomly divided into medication(control) group(n=48) and otopoint pellet-pressing plus medication (treatment) group(n=49). Patients of the control group were given oral Flunarizine capsules(10 mg/time) twice a day, and those of the treatment group received same dosage of Flunarizine and pellet-pressing of otopoints Nao(Brain), Nie (Temporal), Shenmen(Shenmen), Jiaogan(Sympathy) and Pizhixia(Subcortex), 2 min/point, 3 times a day, simultaneously. The treatment was conducted for 1 month. The short-term and long-term clinical effects were evaluated according to Yang and colleagues' methods, and "Guiding principles for clinical research of new TCM drugs (trial)". The contents of plasma 5-HT and CGRP were detected by ELISA. After one month's treatment, of the 48 and 49 patients in the control and treatment groups, 10(20.83%)and 17(34.69%) were under control, 19(39.59%)and 23(46.94%) experienced marked improvement, 10(20.83%)and 7(14.29%)were effective, 9(18.75%) and 2(4.08%) failed, with the total effective rates being 81.25% and 95.92%, respectively. Six months' follow-up survey showed that of the 48 and 49 patients in the control and treatment groups, 4(8.33%)and 11(22.45%) were under control, 20(41.67%)and 24(48.98%)experienced marked improvement, 11(22.92%)and 9(18.37%)were effective, and 13(27.08%) and 5(10.20%)failed, with the total effective rates being 72.92% and 89.80%, respectively. The number of headache attacks, duration of each attack and the degree of headache were significantly decreased after 1 and 6 months' treatment in both groups in comparison with their own pre-treatment (P<0.05). The contents of plasma 5-HT at the time-points of 1 and 6 months were markedly increased (P<0.05), and those of plasma CGRP at the two time points markedly decreased in both groups in comparison with their own pre-treatment (P<0.05). The therapeutic effects of the treatment group were obviously superior to those of the control group in lowering the number of headache attacks, duration of each attack and the degree of headache and plasma CGRP content, as well as in increasing plasma 5-HT levels after 1 and 6 months' treatment (P<0.05). Otopoint pellet-pressing combined with oral administration of Flunarizine can significantly improve the clinical symptoms in patients with migraine without aura, and possess a stable long-term clinical effect, which may be associated with its effect in increasing plasma 5-HT and decreasing CGRP levels.

Plasma Calcitonin Gene-Related Peptide: A Potential Biomarker for Diagnosis and Therapeutic Responses in Pediatric Migraine.

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine.Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA.Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, p = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, p = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, n = 47) than those not (183 ± 54 pg/ml, n = 21) (p = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, n = 14 vs. 67 ± 19 pg/ml, n = 6, p = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives.Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Estimation of calcium requirements for optimal productive and reproductive performance, eggshell and tibial quality in egg-type duck breeders

Optimizing the dietary calcium (Ca) level is essential to maximize the eggshell quality, egg production and bone formation in poultry. This study aimed to establish the Ca requirements of egg-type duck breeders from 23 to 57 weeks of age on egg production, eggshell, incubation, tibial, plasma and ovary-related indices, as well as the expression of matrix protein-related genes. Totally, 450 Longyan duck breeders aged 21 weeks of age were allotted randomly into five treatments, each with six replicates of 15 individually caged birds. The data collection started from 23 weeks of age and continued over the following 35 weeks. The five groups corresponded to five dietary treatments containing either 2.8%, 3.2%, 3.6%, 4.0% or 4.4% Ca. The tested dietary Ca levels increased (linear, P <0.01) egg production and egg mass, and linearly improved (P <0.01) the feed conversion ratio (FCR). Increasing the dietary Ca levels from 2.8% to 4.4% increased (P <0.01) the eggshell thickness and eggshell content. The tested Ca levels showed a quadratic effect on eggshell thickness and ovarian weight (P <0.01); the highest values were obtained with the Ca levels 4.0% and 3.6%, respectively. Dietary Ca levels affected the small yellow follicles (SYF) number and SYF weight/ovarian weight, and the linear response (P <0.01) was significant vis-à-vis SYF number. In addition, dietary Ca levels increased (P <0.05) the tibial dry weight, breaking strength, mineral density and ash content. Plasma and tibial phosphorus concentration exhibited a quadratic (P <0.01) response to dietary Ca levels. Plasma calcitonin concentration linearly (P <0.01) increased as dietary Ca levels increased. The relative expression of carbonic anhydrase 2 in the uterus rose (P <0.01) with the increment of dietary Ca levels, and the highest value was obtained with 3.2% Ca. In conclusion, Longyan duck breeders fed a diet with 4.0% Ca had superior eggshell and tibial quality, while those fed a diet with 3.6% Ca had the heaviest ovarian weights. The regression model indicated that the dietary Ca levels 3.86%, 3.48% and 4.00% are optimal levels to obtain maximum eggshell thickness, ovarian weight and tibial mineral density, respectively.

Short Communication: Decreased Plasma Calcitonin Gene-Related Peptide as a Novel Biomarker for HIV-1 Disease Progression

HIV-1 mucosal transmission in genital epithelia occurs through infection of Langerhans cells and subsequent transinfection of CD4+ T cells. We previously reported that the vasodilator neuropeptide calcitonin gene-related peptide (CGRP), secreted upon activation of sensory peripheral neurons that innervate all mucosal epithelia, significantly inhibits transinfection. To investigate the association between CGRP and HIV-1 during infection, we evaluated circulating CGRP levels in HIV-1-infected patients. Plasma was obtained from combination antiretroviral therapy (cART)-naive or cART-treated patients with primary/acute (PHI) or chronic (CHI) HIV-1 infection, as well as from individuals who naturally control HIV-1 infection, namely exposed seronegatives (ESNs), elite controllers (ECs), and long-term nonprogressors (LTNPs). CGRP plasma levels were measured using an enzyme immunoassay. Compared with healthy HIV-1-negative controls, CGRP plasma levels significantly decreased in PHI patients and even further in CHI patients, but remained unchanged in ESNs, ECs, and LTNPs. Moreover, CGRP plasma levels were restored to baseline upon cART in both PHI and CHI. Finally, CGRP plasma levels directly correlated with CD4+ T cell counts and inversely with viral loads. Altogether, CGRP could serve as a novel diagnostic plasma biomarker for progression of HIV-1 infection. Moreover, administration of CGRP to cART-naive HIV-1-infected patients, to compensate for CGRP decline, could help controlling on-going HIV-1 infection.

Detection and significance of calcitonin gene-related peptide in children with enterovirus 71 infected hand foot and mouth disease

Objective To detect the plasma calcitonin gene-related peptide (CGRP) in children with enterovirus 71(EV71) infected hand foot and mouth disease(HFMD), and explore the relationship between CGRP and the severity of EV71 infected HFMD. Methods Two hundred children with EV71 infected HFMD in Xi′an Children′s Hospital from January 2017 to December 2017 were selected as the research group, and 50 healthy children were selected as control group in the same period.According to the severity of the disease, the research group was divided into the mild group (n=142) and the severe group (n=58). The level of plasma CGRP was detected by ELISA. Results In acute stage, the level of CGRP in children with EV71 infected HFMD was lower than that in control group, and the difference was statistically significant (t=4.235, P<0.001). The level of CGRP in acute stage in severe group[(29.90±5.10)pg/ml] was significantly lower than that of the mild group[(35.51±5.48)pg/ml], and the difference was statistically significant (t=6.615, P=0.001). The level of CGRP in mild group[(35.51±5.48)pg/ml] was slightly lower than that of the control group[(36.63±5.65)pg/ml], but the difference was insignificant (t=1.120, P=0.086). In recovery stage, the level of CGRP in the severe group was obviously higher than that in the acute stage(t=5.924, P=0.003). According to the ROC curve of CGRP in mild and severe EV71 infected HFMD, the critical value of CGRP in mild and severe HFMD was 28.12 pg/ml, and the sensitivity was 80.0% and the specificity was 50.0%. Conclusion The CGRP is associated with the progression of EV71 HFMD, and when CGRP is lower than 28.12 pg/ml, suggesting the possibility of severe HFMD.The decrease of plasma CGRP may be a risk factor for the progression of EV71 infected HFMD. Key words: Hand foot and mouth disease; Enterovirus 71; Calcitonin gene-related peptide

\u03b1-Melanocyte-stimulating hormone directly increases the plasma calcitonin level and involves calcium metabolism in goldfish

The effects of α-melanocyte-stimulating hormone (α-MSH) on calcium metabolism were examined with goldfish. The scales on the left side of goldfish bodies were removed to allow the regeneration of scales under anesthesia. Thereafter, the influences of α-MSH injection (low dose: 0.1 μg/g body weight; high dose: 1 μg/g body weight) on plasma calcitonin (calcium-regulating hormone) and the calcium content of the scales were investigated. Ten days after removing the scales, we measured the plasma calcitonin and calcium content of both regenerating scales on the left side and ontogenic scales on the right side. At both doses of α-MSH injection, plasma calcitonin concentrations in the α-MSH-treated group were significantly higher than those in the control group. The mRNA expressions of α-MSH-receptors were detected in the ultimobranchial glands (secretory organ of calcitonin), indicating that α-MSH directly functions in ultimobranchial glands and promotes calcitonin secretion. Furthermore, we found that the calcium content of regenerating scales in α-MSH-treated goldfish was higher than that in control goldfish, while the calcium content of ontogenic scales on the right side was significantly decreased by α-MSH injection. There was a significant co-relationship between plasma calcitonin and the calcium content of regenerating scales. The mRNA expression of calcitonin receptors in regenerating scales was remarkably higher than that in ontogenic scales. These results imply that calcitonin functions to promote scale regeneration resulting from the inhibition of bone resorption because calcitonin suppresses osteoclastic activity. Thus, we are the first to demonstrate the interaction between α-MSH and calcitonin in teleosts.

A Metabolism-Based Synergy for Total Coumarin Extract of Radix Angelicae Dahuricae and Ligustrazine on Migraine Treatment in Rats

Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still unknown. In this study, the total coumarin extract (TCE) of Radix Angelicae dahuricae (50 mg/kg, orally) reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats (p < 0.05). Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration–time curve of ligustrazine and prolonged its mean retention time in rats (p < 0.05). Besides, the IC50 for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC50 < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix Angelicae dahuricae could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix Angelicae dahuricae and ligustrazine on migraine treatment.

Calcitonin Response to Naturally Occurring Ionized Hypercalcemia in Cats with Chronic Kidney Disease.

BackgroundHypercalcemia is commonly associated with chronic kidney disease (CKD) in cats.ObjectivesTo explore the calcitonin response to naturally occurring ionized hypercalcemia in cats with azotemic CKD, and to assess the relationship of plasma calcitonin with ionized calcium, alkaline phosphatase (ALP), and urinary calcium excretion.AnimalsThirty‐three client‐owned cats with azotemic CKD and ionized hypercalcemia from first opinion practice.MethodsCohort study. Calcitonin was measured with an immunoradiometric assay in heparinized plasma. Simple correlations were assessed with Kendall's rank correlation, and the within‐subject correlations of calcitonin with ionized calcium and other clinicopathological variables were calculated with a bivariate linear mixed effects model.ResultsCalcitonin concentrations above the lower limit of detection (>1.2 pg/mL; range, 1.7–87.2 pg/mL) were observed in 11 of 33 hypercalcemic cats (responders). Blood ionized calcium concentration did not differ significantly between responders (median, 1.59 [1.46, 1.66] mmol/L) and nonresponders (median, 1.48 [1.43, 1.65] mmol/L; P = 0.22). No evidence was found for calcitonin and ionized calcium to correlate between cats (τb = 0.14; P = 0.31; n = 33), but significant positive correlation was evident within individual responders over time (within‐subject correlation coefficient [r within], 0.83; 95% confidence interval [CI], 0.63–0.92). Calcitonin correlated negatively over time with plasma ALP (r within, −0.55; 95% CI, −0.79 to −0.16).Conclusions and Clinical ImportanceCalcitonin does not appear to have an important role in calcium metabolism in cats with CKD.

Effect of Electroacupuncture on Expression of 5-HT7 Receptor in Periaqueductal Gray and Plasma Calcitonin Gene-related Peptide in Migraine Rats

To explore the analgesic effect of electroacupuncture(EA)by modulating 5-hydroxytryptamine 7 (5-HT7) receptor in periaqueductal gray (PAG) and plasma calcitonin gene-related peptide (CGRP). Forty-two male Sprague Dawley (SD) rats were randomly divided into control，model and EA groups, 14 rat in each one. The neurogenic migraine model was established by repeated electrical stimulation on sagittal sinus duramater. Intracranial electrodes were used in the control group without stimuli. The rats in the EA group received EA (0.5－1 mA, 2 Hz/15 Hz) at "Fengchi" (GB 20) for 10 min after dural electrical stimulation, once a day for 6 days. The expression of 5-HT7 receptor in the PAG was assessed by immunofluorescence and Western blot, respectively; plasma CGRP was measured by radioimmunoassay. Compared with the control group, the positive neuron number and protein expression of 5-HT7 receptor in PAG and plasma CGRP increased after model establishment (all P<0.001). The above mentioned indexes were reversed in the EA group compared with those in the model group (the positive neuron number and protein expression of 5-HT7 receptor, P<0.01; plasma CGRP, P<0.05). EA at GB 20 can down-regulate the expression of 5-HT7 receptor in the PAG and reduce the content of plasma CGRP in the rats of migraine.

Ghrelin attenuated hyperalgesia induced by chronic nitroglycerin: CGRP and TRPV1 as targets for migraine management.

Background According to the neurovascular theory of migraine, activation of the trigeminovascular system contributes to the development of migraine. This study examined the effects of chronic intraperitoneal ghrelin (150 µg/kg) treatment on the development of chronic migraine induced by intermittent injection of nitroglycerin 10 mg/kg. Methods Baseline and post-drug (2 h following nitroglycerin injection) mechanical and thermal sensitivity were assessed by von Frey hair and tail immersion tests, respectively on days 1, 3, 5, 7, 9 and 11. Moreover, we investigated the effect of ghrelin treatment on nitroglycerin-induced aversive behavior by using a two-chamber conditioned place aversion paradigm. At the end of behavioral testing, on day 11, animals were sacrificed and plasma concentration of calcitonin gene-related peptide was measured using a rat-specific enzyme-linked immunosorbent assay kit. Also, real time polymerase chain reaction was used to quantify mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid 1 in the trigeminal ganglion. Results Our results indicated that nitroglycerin activated the trigeminovascular system, which was reflected by mechanical and thermal hypersensitivity and elevation of mRNA expression of calcitonin gene-related peptide and transient receptor potential vanilloid-1, as migraine markers, and plasma calcitonin gene-related peptide levels. Moreover, chronic nitroglycerin injection induced conditioned place aversion and body weight loss. Nevertheless, ghrelin modulated nitroglycerin-triggered changes in transient receptor potential vanilloid-1 and calcitonin gene-related peptide expression, and mitigated nitroglycerin-induced hyperalgesia. Conclusion These results provide the first convincing evidence that ghrelin has a modulating effect on central sensitization induced by chronic intermittent nitroglycerin, and its antinociceptive effect may be related to a reduction of these factors in the trigeminal ganglion.

Circadian Alteration of Plasma Calcitonin Gene-Related Peptide, Endothelin-1 and Hemodynamic Parameters In Normotensive and Hypertensive Rats

Circadian Alteration of Plasma Calcitonin Gene-Related Peptide, Endothelin-1 and Hemodynamic Parameters In Normotensive and Hypertensive Rats

Should serum calcitonin be routinely measured in patients presenting with thyroid nodule?

The European Thyroid Association recommends serum calcitonin measurement in thyroid nodule cases. In contrast, the American Thyroid Association is ambivalent. In this institution, thyroid nodules cases are subject to a multidisciplinary evaluation of the clinical history and examination, ultrasound and scintigraphy, CT scan and sometimes MRI scan, biochemistry and histopathology of biopsies. We report on the current use of plasma calcitonin measurements in the context of changing practice which has not included screening of all thyroid nodules. Laboratory records were searched from the beginning of January 2010 to the end of April 2016 for all serum calcitonin measurements. There were 44 patients (30 females, age range 31 to 87 years with median 57.5) and 14 males, age range 20 to 85 years with median 53.4 years) who had a serum calcitonin measured. Of these 33 patients did not have a detectable serum calcitonin. There were 3 patients who had an initial elevated serum calcitonin which became undetectable over time. Over the same time period, a total of 2070 patients presented with thyroid nodules. Medullary thyroid cancer (MTC) was found in 7 cases. Thus assuming all MTC cases had calcitonin measured, MTC is 7 of 341 (2.05%) of the total thyroid cancer burden at the hospital and 7 of 2070 (0.338%) of all thyroid nodules. Our practice is not to routine screen all nodules for MTC. Because patients with a nodule are subjected to ultrasound scanning and biopsy, when the nodule size is greater than 5 cm or when there is a modifying ultrasound or clinical characteristic, the consensus at the multidisciplinary conference on thyroids rather than universal calcitonin screening of all nodules is the better option in our judgement.

Plasma Calcitonin Levels and miRNA323 Expression in Medullary Thyroid Carcinoma Patients with or without RET Mutation

Background:Medullary thyroid cancer (MTC) is an endocrine tumor featuring parafollicular or C-cell differentiation, with calcitonin as a specific biomarker in MTC diagnosis. Germline mutations in the RET proto-oncogene are considered responsible for its familial occurrence and somatic mutations can cause sporadic lesions. MicroRNAs can act as oncogenes or tumor suppressors by inhibiting the expression of target genes.. The aim of this study was to investigate relationships between plasma levels of calcitonin and miRNA323 expression in MTC patients with or without RET mutation.Methods:In this cross-sectional study, MTC lesions (based on pathological confirmation) were investigated. Genomic DNA was extracted and Exons 10 and 11 of RET were genotyped using PCR-sequencing. Division was into two groups of 43 cases each with or without mutation. Plasma levels of calcitonin were determined in both.Results:miRNA323 was measured using real-time-PCR. After performing normality tests, independent T-tests and Mann Whitney tests were used for the statistical comparison of parametric and nonparametric data, respectively. Plasma levels of calcitonin were significantly higher in MTC cases without a RET mutation compared to those with a mutation.Conclusion:There was no significant difference between the two groups regarding the expression of miRNA323 so that this parameter could not be used as a bio-index germ line mutations in MTCs. However, determination of calcitonin levels in plasma might be helpful in this regard.

Pharmacodynamic action and mechanism of Du Liang soft capsule, a traditional Chinese medicine capsule, on treating nitroglycerin-induced migraine

Ethnopharmacological relevanceDu Liang soft capsule (DL) is a traditional Chinese medicine for treating migraines; it is made from two Chinese herbs, including LigusticumstriatumDC., root; Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav., root. Aim of the studyIn the present study, we aimed to elucidate the pharmacodynamic action of DL and its mechanism in an animal model of migraines induced by glyceryl trinitrate (GTN). Materials and methodsSixty rats were randomly divided into six groups, including a normal control group, model control group, positive group (Sumatriptan 0.006gkg−1), and three DL groups (0.44, 1.31 and 3.93gkg−1). All rats were intragastrically treated with the corresponding treatment for 7 consecutive days, and they were subcutaneously injected with GTN (10mgkg−1) 30min after the last treatment, except in the normal control group. After model establishment, the behaviors of all rats, including head scratching, cage climbing, and the development of red ears were observed continuously by digital camera every 30min for 3h. Four hours after GTN treatment, all rats were anaesthetized and the blood and tissue samples were collected. Plasma calcitonin gene related to peptide (CGRP) and endothelin (ET) levels were measured using the radioimmunoassay method, and serum NO was determined by the colorimetric method. Afterwards, the brainstem tissues were dissected and washed with physiological saline, and divided evenly into two parts. One part was used to test the monoamine levels, including levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA), by the fluorometric method, and the other part was used to determine the nuclear factor kappaB (NF-κB) p65, nuclear c-fos, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β (IL-1β), and cyclooxygenase-2 (COX-2) levels by Western blot analysis. ResultsIn the pharmacodynamic action assay, DL (1.31 and 3.93gkg−1) greatly improved the abnormal behaviors of migraine rats, including head scratching and cage climbing, and the development of red ears. In the mechanism assay, compared with the control group, the plasma CGRP and serum NO levels and the brainstem 5-HT, NE and DA levels in the DL administration groups were significantly decreased; and the plasma ET levels were remarkably increased. Moreover, down-regulation of NF-κB p65, c-fos and pro-inflammatory cytokines, including iNOS, IL-1β and COX-2 in the brainstem in the DL administration groups were observed by Western blot analysis. ConclusionsThe above results suggested that DL has a therapeutic effect on migraines, and its mechanism may be related to adjusting the level of neurotransmitters and vasoactive substances, consequently relieving neurogenic inflammation.

Anesthetic Management of Clinically Silent Familial Pheochromocytoma with MEN 2A: A Report of Four Cases.

Familial pheochromocytomas are commonly associated with multiple endocrine neoplasia type 2 (MEN 2) syndrome. Majority of the patients present with normal clinical and biochemical parameters in the preoperative period, the incidence of hypertension being only 50%. Even though patients may be clinically asymptomatic, surveillance and proper preoperative evaluation is important, as surgery for associated tumors may precipitate a hypertensive crisis and result in severe complications. A family of 19 members, of which 12 were positive for MEN 2A syndrome, presented to our hospital. Seven of the 12 patients had pheochromocytoma and medullary thyroid carcinoma (MTC), while the other 5 had only raised plasma calcitonin levels. Two of the 7 patients presented with bilateral pheochromocytoma and underwent an open adrenalectomy. The other 5 patients had a left-sided adrenal tumor and underwent left laparoscopic adrenalectomy under combined general and epidural anesthesia. We present our experience with four of these five cases. We here state that how paucity of literature on perioperative preparation of clinically and biochemically silent pheochromocytomas led to serious intraoperative complications in one of four cases.