Aberrant expression of calcitonin gene-related peptide and its correlation with prognosis in severe childhood pneumonia

OBJECTIVES: The purpose of this study was to evaluate the relationship between the serum levels of calcitonin gene-related peptide (CGRP) and the prognosis of pediatric patients with severe pneumonia. METHODS: Children diagnosed with severe pneumonia (n=76) were stratified into the survival (n=58) and non-survival groups (n=18) according to their 28-day survival status and into the non-risk (n=51), risk (n=17) and high-risk (n=8) categories based on the pediatric critical illness score (PCIS). Demographic data and laboratory results were collected. Serum CGRP levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic (ROC) curve was generated to determine the cutoff score for high CGRP levels. RESULTS: Serum CGRP levels were significantly higher in the survival group than in the non-survival group and were significantly higher in the non-risk group than in the risk and high-risk groups. The ROC curve for the prognostic potential of CGRP yielded a significant area under the curve (AUC) value with considerable sensitivity and specificity. CONCLUSION: Our findings show that CGRP downregulation might be a diagnostic marker that predicts the prognosis and survival of children with severe pneumonia.

Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

effect of endurance training in changes of blood lactate and plasma calcitonin gene related peptide levels in type 2 diabetic rats

Streptozotocin-induced type2 diabetes causes functional and metabolic changes in some tissues and subsequently produces some intermediates and substances which enter the circulation. On the other hand, endurance training can modify the amount of these substances. In this study, the effects of diabetes and endurance training on resting levels of blood lactate and plasma calcitonin gene- related peptide [CGRP] were investigated. Fifty rats were divided into 4 groups including control nondiabetic [n=10] training nondiabetic [n=10] nontraining diabetic [n=15] and training diabetic. Diabetes was induced by feeding with high fat diet HFD and injecting STZ. The training groups underwent an endurance training program on treadmill. Blood Lactate concentration was measured by a lactate kit and plasma CGRP concentration was determined by enzyme immunoassay kit [EIA]. In the control nondiabetic, training nondiabetic, nontraining diabetic control and training diabetic groups, the restig values of blood lactate were 2.4, 2.08, 4.5, 3.7 [mmol/L] and plasma CGRP values were 0.40, 0.35, 4.9,3.0 [ng/ml], respectively. Resting levels of circulating lactate and CGRP were higher in diabetic subjects than in control nondiabetic rats and endurance training decreased resting value of blood lactate in diabetic rats but did not change the plasma CGRP. Thus, it seems that the role of endurance training in ameliorating diabetes is due to decreasing resting level of blood lactate, but not plasma CGRP

possible role of calcitonin gene-related peptide in estradiol cardioprotection in cases of isoproterenol-induced myocardial ischemia in rats

Relative to its metabolic requirements, heart tissue is one of the most poorly perfused in the body, and ischemia resulting from compromised coronary blood flow can have serious detrimental effects. Estrogen has been suggested to modulate vascular physiology and function from a variety of studies in cellular, animal and human models. Genetic deletion of estrogen receptor results in the development of hypertension in middle-aged male and female mice, resulting in endothelial dysfunction and oxidative stress. Calcitonin gene-related peptide [CGRP], a well characterized vasoactive neuropeptide, is a 37 amino acid peptide resulting from the specific maturation processes of calcitonin gene products. It was discovered in 1982. CGRP is considered to be a neuromediator of particular importance in the cardiovascular system. Regardless of which estrogen receptor mediates cardioprotection, the mechanisms by which estrogen elicits cardioprotection in females are poorly understood. Hence, the present study was conducted in order to investigate the possible role of CGRP in cardioprotection offered by estradiol pretreatment in cases of isoproterenol-induced myocardial ischemia in rats. The present study was conducted on 24 adult female albino rats, weighing 150-200 gms, fed ad libitum, divided into 3 groups: Group [I]: 8 sham-operated rats that served as control. Group [II]: 8 rats that underwent ovarectomy [day 0] and 7 days later, they were pretreated with estradiol subcutaneously [0.25 mg/kg] for 21 day period. Group [III]: 8 rats that also underwent ovarectomy but stayed without estradiol treatment for 28 days. Group II and III rats were, thereafter, intoxicated with isoproterenol subcutaneously [85 mg/kg] for 2 consecutive days to induce myocardial ischemia. Then, all rats were killed. Blood was collected and serum was assayed for blood lipids, creatine kinase and lactate dehydrogenase activities, serum CGRP was also measured. Heart tissues were homogenized and estimation of cardiac CGRP was done. Serum creatine kinase and lactate dehydrogenase activities were significantly increased in group III rats as compared to group I and II. Serum triglycerides and total cholesterol levels also showed a significant increase in group III rats as compared to group I and II. Serum and cardiac CGRP were significantly increased in group II [estradiol-pretreated rats] as compared to group I and III. Significant positive correlation was found between serum and cardiac levels of CGRP, also between both and serum triglycerides. From the previous results, we can conclude that estradiol may exert a protective effect in cases of isoproterenol-induced myocardial ischemia in rats through increasing serum and cardiac levels of CGRP, decreasing serum lactate dehydrogenase and creatine kinase activities and lowering serum triglycerides and total cholesterol levels as compared to estradiol-untreated rats

Evaluation of calcitonin gene- related peptide in hypertension: a clinical and experimental study

Calcitonin gene-related peptide [CGRP] is an extremely potent vasodilator neuropeptide that is widely distributed in the perivascular sensory nerves. To clarify the exact role of CGRP in hypertension in both essential hypertension patients and experimentally induced hypertension in rats. 15 patients with untreated essential hypertension and 15 age and sex matched healthy controls were subjected to physical examination, resting ECG, two-dimensional echocardiography, abdominal ultrasound, Doppler study of renal vessels, and laboratory tests including estimation of serum CGRP, malondialdehyde [MDA; as an oxidative stress marker], renal functional parameters and other essential investigations. In the experimental study, hypertension was induced in 15 male albino rats by uninephrectomy and 0.9% saline in drinking water for 6 weeks [uninephrectomy-salt model]. 15 matched healthy male albino rats [controls] were sham operated and given tap water. Rats were subjected to mean arterial pressure [MAP] measurement, using a pressure transducer, and laboratory tests including serum CGRP, MDA and renal function tests. Compared with normotensive controls, essential hypertension patients had a significantly higher mean serum creatinine [P= 0.011], urinary albumin excretion [UAE], and serum MDA versus a significantly reduced CGRP [P<0.001]. Echocardiography revealed subtle hypertensive findings in only 3 patients. All ECGs were normal. Hypertensive rats showed a significantly higher mean blood urea, serum creatinine, UAE, serum MDA, and also CGRP than control rats [P<0.001]. In hypertensive patients, the only observed correlation was a positive correlation between the systolic blood pressure and serum MDA [r =0.52, P =0.037]. In hypertensive rats, a positive correlation was observed between each of MAP, UAE and serum MDA [r =0.65, P =0.008 and r =0.62, P = 0.012] and also between MAP and serum CGRP [r =0.59, P =0.017], versus an inverse correlation between UAE and CGRP [r = -0.54, P =0.026]. In addition, a strongly positive correlation was observed between serum MDA and CGRP in the hypertensive rats [r =0.77, P<0.001]. Patients with essential hypertension have diminished CGRP levels. Hypertension is associated with increased oxidative stress. CGRP is important in protection against hypertension-induced renal damage. These data shed light on a potentially therapeutic role of CGRP and may be antioxidants in the management of hypertension, including the use of medications that can enhance CGRP release, or increase the vascular sensitivity to this neuropeptide

Effect of chronic renal impairment on adrenomedullin levels in rats

Adrenomedullin [ADM] is a novel and potent vasodilator peptide with a partial structural homology to calcitonin gene related peptide [CGRP]. This study was carried out on 18 albino rats divided into three equal groups [n=6]. Group I: sham operated normal rats; group II subtotally nephrectomized [SN X] rats sacrificed four' weeks postoperatively Group III SNX rats sacrificed eight weeks postoperatively. All these groups were studied for the following parameters, blood urea, plasma nitrite, plasma and tissue adrenomedullin concentrations. This study revealed a significant elevation in plasma urea level in groups II and III compared to group I also groups II and III showed a significant rise in both plasma and kidney tissue adrenomedullin levels while plasma and urinary levels of nitrites showed significant decrease as compared to controls