Serum Adrenomedullin Levels Research Articles

Calcitonin Gene-Related Peptide and Adrenomedullin Levels During Ictal and Interictal Periods in Patients With Migraine.

Background Peptides related to calcitonin gene-related peptide (CGRP) have been suggested to have a role in migraine. Adrenomedullin (AM) might be a candidate molecule because it is related to pain pathways in the peripheral and central nervous systems and uses the same receptors as CGRP. Methodology In this study, we examined the serum CGRP and AM levels during unprovoked ictal and interictal periods of 30 migraine patients as well as 25 healthy controls. Another focus of this study was on the association of CGRP and AM levels with clinical features. Results Mean serum AM levels were 15.80 pg/mL (11.91-21.43 pg/mL) in the ictal and 15.85pg/mL (12.25-19.29 pg/mL) in the interictal periods in the migraine group and 13.36pg/mL (10.84-17.18 pg/mL) in the control group. Mean serum CGRP levels were 2.93pg/mL (2.45-3.90 pg/mL) in the ictal and 3.25pg/mL (2.85-4.67 pg/mL) in the interictal periods in the migraine group and 3.03pg/mL (2.48-3.80 pg/mL) in the control group. There were no statistical differences between ictal and/or interictal AM and CGRP levels (p = 0.558 and p = 0.054, respectively) which were also comparable with the results of the control group (p = 0.230, p = 0.295, p = 0.987, p = 0.139, respectively). Ictal serum CGRP and/or AM levels did not correlate with any of the reported clinical features. Conclusions Serum AM and CGRP levels are similar in interictal and unprovoked ictal periods in migraine patients and as well in controls. These results do not indicate that these molecules do not have a role in migraine pathophysiology. Considering the broad mechanisms of action of peptides in the CGRP family, further studies are needed in larger cohorts.

Serum level of Adrenomedullin in patients with primary knee osteoarthritis; relation to disease severity

BackgroundAdrenomedullin (AM) is a peptide which was suggested to be involved in the pathogenesis of osteoarthritis through its anti-inflammatory and anti-apoptotic effect. AM was found to be elevated in some inflammatory rheumatic diseases as rheumatoid arthritis and ankylosing spondylitis.The current study was performed to measure serum Adrenomodullin (AM) concentrations in patients with primary knee osteoarthritis (KOA) and to assess association with severity of the disease. The study was performed on 50 patients with primary KOA diagnosed according to American College of Rheumatology (ACR) Revised Criteria for Early Diagnosis of Knee Osteoarthritis and 20 age- and sex-matched controls with no clinical features of KOA. The Kellgren and Lawrence (KL) classification was used to evaluate the disease severity of knee OA. Disease activity was assessed by The Western Ontario and McMaster Universities Arthritis Index (WOMAC). Blood samples had been collected from patients with OA and controls for assessing Adrenomodullin in patients’ sera by ELISA.ResultsThere were a significant increase in serum Adrenomedullin concentrations in KOA patients compared to controls (10.64 ±19.2 ng/ml vs. 1.39 ±1.6 ng/ml in cases and controls respectively) (p value = 0.036). There was positive significant correlation of serum Adrenomedullin levels with KL grades (r=0.608, p value <0.001). OA patients with VAS score >6 have significantly higher serum Adrenomedullin levels than OA patients with VAS Score <6. No detected significant correlation between any of (patients’ age, BMI, disease duration, tenderness score, and WOMAC score) with serum Adrenomedullin levels among studied OA cases (p values >0.05).ConclusionThis study concluded that serum Adrenomedullin (AM) level is elevated in patients with KOA and is positively correlated with the severity of disease.

The effect of swimming training on adrenomedullin levels, oxidative stress variables, and gastrocnemius muscle contractile properties in hypertensive rats

ABSTRACT Introduction/Aim: Regular exercise may have beneficial effects on high blood-pressure, as shown in different types of experimental hypertension models in rats. The present study aims to investigate the effects of 6-week swimming training on blood pressure, oxidative stress variables of selected tissues, serum adrenomedullin (ADM) levels, and in situ muscle contraction in rats with hypertension induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of endothelial nitric oxide synthases (eNOs). Materials and Methods: Twenty-six male Sprague Dawley, 8 weeks of age, rats were randomly divided into four groups: (I) normotensive (C), (II) normotensive + exercise (E), (III) hypertensive (L), and (IV) hypertensive + exercise (LE). Hypertension was induced by the oral administration of L-NAME (60 mg/kg) for 6 weeks. Exercise was performed 5 times (1-h each) per week for 6 weeks. At the end of the experiment, blood and tissue samples (the gastrocnemius muscle, heart, kidney, and thoracic aorta) were collected following contractile properties of the gastrocnemius muscle in situ weredetermined. In the collected tissues, oxidative stress (e.g., lipid oxidation and antioxidant enzyme activity) and serum ADM levels were measured. 6-week L-NAME administration per se (Group L) led to a significant increase in systolic and diastolic blood pressure compared to other groups. Results: Importantly, 6-week exercise caused a protective effect of high blood pressure in the rats received L-NAME (Group LE). The level of ADM was lower in the rats received L-NAME than that of the control group. L-NAME increased lipid peroxidation in the thoracic aorta and decreased superoxide dismutase in the heart, kidney and muscle, and decreased catalase and glutathione in the heart. However, the exercise intervention did not have protective effect on the L-NAME-mediated oxidative damage in the collected tissues. Conclusion: In conclusion, 6-week exercise intervention rescued rats from high blood pressure, but did not have ameliorative effect on the decreased ADM levels.

Comparison of the serum adrenomedullin levels in pregnant women between normotensive and complicated with preeclampsia

GIRIŞ ve AMAC: One surulen cesitli mekanizmalara ragmen, preeklampsinin patogenezi halen tam olarak anlasilamamistir. Adrenomedullin kan basinci regulasyonuna katkida bulunan guclu vasodilator ve natriuretik bir peptid olup hipertansif hastaliklar ile iliskilidir. Buna karsin bu peptidin preeklampsiyle iliskisi hakkindaki veriler farklilik gostermektedir. Bundan oturu bu calismada biz maternal serum adrenomedullin konsantrasyonlarinin preeklamptik gebeliklerde artis gosterip gostermedigini degerlendirmeyi amacladik. YONTEM ve GERECLER: 41 preeklamptik ve 44 normotensiv gebe kadin yas ve gestasyonel yas eslesmeli olarak prospektif sekilde calismaya dahil edildiler. Preeklampsi tanisi Amerikan Obstetrisyenler ve Jinekologlar Birligi (ACOG) kriterleri temel alinarak konuldu. Serum adrenomedullin konsantrasyonlari ELISA (Enzyme-Linked ImmunoSorbent Assay) teknigi kullanilarak olculdu. BULGULAR: Hem sistolik hem de diastolik kan basinci duzeyleri preeklamptik grupta daha yuksek saptandi. Maternal serum adrenomedullin konsantrasyonlari iki grup arasinda anlamli fark gostermiyordu (34.29±8.52 pmol/L 'e karsin 33.83 ±6.21 pmol/L;p=0.29). Ne sistolik ne de diastolik kan basinclari ile adrenomedullin arasinda anlamli korelasyon saptanmadi (p>0.05) TARTIŞMA ve SONUC: Her ne kadar bu calisma populasyonunda preeaklamptik maternal serum adrenomedullin konsantrasyonlari artis gostermese de; bu vasodilator peptidin preeklampsi patogenesindeki olasi rolunun daha buyuk prospektif calismalarda detayli olarak incelenmesi gerektigi onerilir.

Adrenomedullin—A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0–18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7–10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1–18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7–10. In the sepsis group, PCT levels on days 7–10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7–10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

The neuropeptide adrenomedullin, could it be linked to renal involvement and disease activity in systemic lupus erythematosus?

Aim of the workThe aim of this study was to assess adrenomedullin level in systemic lupus erythematosus (SLE) patients with nephritis compared with those without and healthy controls and to correlate adrenomedullin level with SLE disease activity. Patients and methodsSerum adrenomedullin was evaluated in 60 SLE patients (mean age 27.7±8.25years) and in 20 matched controls. The SLE patients were divided into two groups: Group I (with nephritis) and Group II (without) (30patients each). The SLE disease activity index (SLEDAI) was assessed. ResultsThe median serum adrenomedullin levels were significantly higher in SLE patients (7.4ng/ml) compared to healthy controls (3.1ng/ml) (p<0.001). It showed a statistically significant difference between group I (8.8ng/ml) and II (6.1ng/ml) (p<0.01). A significant relation was observed between the level of serum adrenomedullin with the neuropsychiatric manifestations (p=0.006) and vasculitic lesions (p=0.014) in group II patients and with pulmonary hypertension (p=0.04), oral ulcers (p=0.03), and serositis (p=0.02) in group I. A significant negative correlation was found in group I patients between adrenomedullin and 24h protein/day (r=−0.38, p<0.05), as well as platelets & C4, and with C3 in group II as well as a highly significant correlation between SLEDAI and adrenomedullin level in SLE patients (r=0.76, p<0.001) and steroid dose (p<0.001). ConclusionSerum AM is elevated in SLE especially in lupus nephritis patients & correlates with lupus disease activity. It is negatively associated with urine protein excretion per 24h in the group of lupus nephritis patients. Serum AM may be considered among biological markers in SLE.

Clinical outcome in cardiorenal patients related to coronary computed tomography angiography and serum adrenomedullin

Background: Adrenomedullin is present in numerous human body tissues and its powerful vasodilatatory activity is thought to play role in cardiovascular/renal homeostasis and possibly in atherosclerosis. We conducted a prospective 2-year study of one hundred twenty-three patients with chronic kidney disease (CKD). Clinical outcome was analyzed to coronary computed tomography angiography (CCTA) findings and serum adrenomedullin levels. Methods: We determined plasma mid-regional pro-adrenomedullin (MR-proADM) levels using sandwich immunoassay in patients (pts) on stage 2 to 5 CKD (glomerular filtration rate - GFR < 90 ml/min/1.73 m2). Coronary artery calcification (CAC) and noninvasive coronary angiograms were performed by 64-multi-detector computed tomography (Siemens, Germany). The presence of stenosis ≥ 50% during CCTA was considered as significant. The degree of coronary artery calcification was assessed using the Agatston calcium score method. Results: We studied consecutive 123 pts with suspected coronary artery disease (mean age 62.5±10.7 years, 57.7% male, arterial hypertension 89.2%, type 2 diabetes 25.2%, 29.0% had a history of tobacco use and 38.2% were on regular haemodialysis- mean 51.7 months, ranging from 3 to 252 months). On CCTA, 76 pts (65.0%) had no coronary artery disease (CAD),in 29 pts (24.8%) one significant epicardial stenosis and in 12 (10.3%) multivessel disease were documented. The mean MR-proADM plasma levels and CAC score were 1.4 nmol/l and 472.8, respectively. MR-proADM correlated with CAC (r=0.20; p=0.02), GFR (r=-0.75; p<0.001), total cholesterol and LDL-cholesterol (r=-0.36; p=0.02 and r=-0.34; p= 0.001). During follow-up period (18.4±6.2 months) 7 cardiovascular deaths were occurred and 1 patient underwent percutaneous coronary intervention for unstable angina. The main characteristics in pts with cardiac events or eventfree survival were the following: serum MR-proADM (2.5 vs 1.3 nmol/l), CAC (663.7 vs 462.5). When we compared these variables to cardiac events only significant difference was documented in MR-proADM levels (p=0,04). Otherwise, areas under receiver operating characteristic curve (AUC) for prediction of cardiovascular mortality were 0.82 (95% CI 0.67-0.97), 0.75 (95% CI 0.50-0.99) and 0.64 (95% CI 0.29-0.99) for MR-proADM vs duration of hemodialysis and CAC. Conclusions: Coronary computed tomography angiography and serum adrenomedullin represent new alternative diagnostic tools for risk stratification in special group of cardiorenal patients.

Relationship between neonatal adrenomedullin and bilirubin levels

Introduction: Oxidative stress and inflammation are the basic molecular mechanisms in bilirubin neurotoxicity. We aimed to investigate the relationship between serum bilirubin and an antioxidant, anti-inflammatory and neuroprotective peptid, adrenomedullin (AM) levels.Methods: The correlation between serum bilirubin and AM levels was investigated in a total of 87 newborns. Newborns were further divided into two groups according to the serum bilirubin levels. Group I (with significant hyperbilirubinemia) and Group II (without significant hyperbilirubinemia) were compared with respect to demographic, anthropometric and biochemical parameters including serum AM levels.Results: In the correlation analysis, a significant positive correlation was detected between serum indirect bilirubin and AM levels in 87 newborns (p < 0.001, r = 0.945). In demographic, anthropometric and biochemical comparison of the two study groups, serum indirect bilirubin levels were 21.53 ± 3.59 and 9.37 ± 4.87 mg/dl in Groups I and II, respectively (p < 0.001), and serum AM levels were 1.45 ± 0.06 and 1.28 ± 0.07 ng/ml in Groups I and II, respectively (p < 0.001)Conclusion: AM probably plays a significant role in adverse effects and neuronal injury steps of significant hyperbilirubinemia. In parallel with the results of this study the role, effects and physiopathological basis of AM in neonatal hyperbilirubinemia should be established especially with further animal studies. Results of this study may be used in establishing reference values for AM as there are very limited number of studies in newborns.

Anxiety disorders are associated with increased plasma adrenomedullin level and left ventricular hypertrophy in patients with hypertension

Objective: To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension.Methods: Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients.Results: There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21 ± 88.81% versus 56.01 ± 7.85%, p > 0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05 ± 9.42 versus 123.57 ± 7.01 g/m2, p = 0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97 ± 5.48 versus 18.32 ± 6.97 ng/L, p = 0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r = 0.734, p < 0.05) and control group (r = 0.592, p < 0.05).Conclusion: Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.

ST2 and Adrenomedullin in Heart Failure

ST2 is the receptor for interleukin-33, a cytokine with antihypertrophic and antifibrotic effects on the myocardium. Serum levels of the soluble form of ST2 serve as a biomarker for ventricular biomechanical strain and provide prognostic information in patients who have symptomatic heart failure. Adrenomedullin is a vasoactive peptide whose actions run counter to the physiologic derangements of clinical heart failure. It appears that measurements of serum adrenomedullin levels can be used to identify those patients who have advanced heart failure and who are at increased risk for heart failure-related death.

Mechanisms responsible for pulmonary hypertension

Mechanisms responsible for pulmonary hypertension

Adrenomedullin is increased in the portal circulation during chronic sepsis in rats

Background A clinical hallmark of sepsis is an early, hyperdynamic cardiac phase (increased cardiac output) that degrades to a hypodynamic phase, which results in poor gut perfusion and subsequent gastrointestinal (GI) hypoxemia, tissue ischemia, necrosis and loss of gut barrier function. Studies in rat cecal-ligation and puncture suggest that the potent vasodilator adrenomedullin (AM) might initiate or maintain the hypodynamic phase. We hypothesize that AM expression is increased in acute Escherichia coli bacteremia and chronic E coli-Bacteroides fragilis sepsis. Methods Acute bacteremia: male Sprague-Dawley rats were anesthetized (urethane/α-chloralose), tracheotomized, and cannulated for monitoring blood pressure (MABP) and heart rate (HR) and for infusion of E coli (10 9 colony-forming units [CFU] E coli per 1 mL normal saline) and blood sampling. Arterial blood was withdrawn for arterial blood gas (ABG) measurements every 60 minutes. After 6 hours, we harvested lung, liver, kidney, spleen, and small intestine tissue samples and drew arterial and portal blood for AM enzyme-linked immunosorbent assay (ELISA). Chronic sepsis: a sterile gauze pad was implanted and animals recovered for 5 days. Twenty-four hours (10 9 CFU E coli and 10 9 CFU B fragilis per 1 mL normal saline; 1 injection) or 72 hours (2 injections) after the inoculation of the back sponge, rats were anesthetized, intubated, and cannulated as above. MABP, HR, and ABG were measured for 1 hour before tissue and serum harvest for AM ELISA. Results Sepsis increased HR and MABP in all groups. Acute sepsis caused a respiratory alkalosis and pH was also elevated in chronic sepsis. Serum AM levels were increased in all groups compared with baseline and remained elevated at every time point, but were not different between saline controls and septic animals at any time point, except for the portal serum from the 72-hourr chronic sepsis, which was elevated. Conclusions These data suggest that surgical manipulation alone is sufficient to stimulate AM secretion, most probably from endothelial cells. While the AM levels were decreasing at 72 hours compared with 6 hours or 24 hours in the arterial blood and the saline control portal blood, it remained elevated in the septic portal samples, suggesting that the sepsis-induced increase of AM was derived from the gut by a different mechanism than that which elevated arterial serum levels.