Plasma Adrenomedullin Levels Research Articles

Epicardial adipose tissue and its association to plasma adrenomedullin levels in patients with metabolic syndrome

ObjectiveTo assess the association between epicardial adipose tissue (EAT) thickness and plasma adrenomedullin plasma levels in patients with metabolic syndrome (MS). MethodsTwenty-one patients (12 females and 9 males) with MS according to the International Diabetes Federation guidelines, aged 22–58 years, were enrolled into the study and compared to 19 age-matched control subjects without MS. Plasma glucose, lipid, and adrenomedullin levels were assessed. EAT, left ventricular mass, and carotid intima–media thickness were evaluated by transthoracic two-dimensional echocardiography. ResultsNo statistically significant differences were found between the groups in age, sex, and height. Body weight, abdominal circumference (AC), body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly higher (p=0.0001) in MS patients; this group also showed significantly higher glucose (p=0.001), total cholesterol (p=0.01), LDL-C (p=0.03), VLDL-C (p=0.005), triglyceride (p=0.002), Tg/HDL ratio (p=0.0001), and plasma adrenomedullin (3.49±1.21 vs 1.69±0.92ng/mL; p=0.0001) levels and lower HDL-C (p=0.02) levels as compared to the control group. EAT was significantly thicker in MS patients compared to the control group (8.45±3.14 vs 5.43±0.96; p=0.0001), showed a positive correlation to BMI (r=0.347; p=0.02), AC (r=0.350; p=0.02), DBP (r=0.346; p=0.02), and adrenomedullin levels (r=0.741; p=0.0001). In multiple linear regression analysis, adrenomedullin was the only parameter associated to EAT (R2=0.550; p=0.0001). ConclusionIn this small patient group, a statistically significant association was found between EAT and plasma adrenomedullin levels, which may be considered as a potential biomarker of MS.

Plasma adrenomedullin levels in children with asthma: Any relation with atopic dermatitis?

BackgroundAsthma is a chronic, inflammatory disease of the airway, and adrenomedullin (ADM) may have some effects against bronchoconstriction. However, the role(s) of ADM in asthmatic children have not been evaluated yet. The aims of this study were to determine if there are any changes in plasma ADM levels during acute asthma attack, and to search for any association between allergen sensitivity and ADM level in asthmatic children. MethodsTwenty-seven children with acute asthma attack, ranging in age from 5 to 15 years were investigated and compared with 20 controls. Plasma ADM levels (ng/mL) were measured by ELISA method. ResultsNo significant difference was found in ADM levels between the controls and patients in either the acute attack or remission period. Plasma ADM levels were significantly higher in the acute attack (p=0.043) compared to the remission period in patients who were considered as having a “severe attack” according to GINA (Global Initiative for Asthma) classification. There were statistically significant correlations between the patients’ AlaTOP and Food Panel 7 levels and plasma ADM levels in the acute attack period (p=0.010, p=0.001, respectively). The ADM levels in patients with a history of atopic dermatitis were significantly higher in the acute attack period compared to those without a history of atopic dermatitis (p=0.007). ConclusionWe speculate that ADM may have a role in children with atopic dermatitis, and may also have a role in the immuno-inflammatory process of asthma.

Plasma adrenomedullin level is related to a single nucleotide polymorphism in the adrenomedullin gene

Adrenomedullin (ADM) plays an important role in inflammation and is a marker of future cardiovascular events. We studied common single nucleotide polymorphisms (SNPs) in the gene encoding ADM and their relationship with the plasma levels of ADM and other inflammatory markers. Plasma ADM, interleukin 6 (IL6), fibrinogen, and C-reactive protein (CRP) were measured in 476 subjects from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study-2. Four tag SNPs in ADM were genotyped. Plasma ADM level increased with decreasing plasma IL6 level (β=-0.116, P=0.014). Plasma ADM level was not related to plasma levels of CRP and fibrinogen, and other clinical characteristics, except age (P=0.049). The four SNPs, rs3814700, rs11042725, rs34354539, and rs4910118, had minor allele frequencies of 31.1, 28.7, 33.8, and 23.4% respectively. Carriers of the minor allele of rs4910118 had a mean plasma ADM level that was 10.5% (95% confidential interval: 2.5-17.8%) lower than the non-carriers (β=-0.115, P=0.011). Haplotype analysis revealed a similar significant association with plasma ADM (P=0.040). In multivariate analysis, the presence of the minor allele of rs4910118, but not plasma IL6, was independently associated with plasma ADM (P=0.010). Plasma ADM correlates with plasma IL6 level, consistent with its role in inflammation. It is related to an SNP common in Chinese, independent of other covariates. ADM genotype should be included in future studies of cardiovascular risk prediction.

Adrenomedullin: possible predictor of insulin resistance in women with polycystic ovary syndrome.

The aim of the study was to investigate adrenomedullin (ADM) levels and its relation with insulin resistance in women with polycystic ovary syndrome (PCOS). Twenty-nine women with PCOS and 29 age- and body mass index (BMI)- matched control subjects were included in the study. PCOS was defined according to criteria by the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM)-sponsored PCOS consensus workshop group. A full clinical and biochemical examination including basal hormones and metabolic profile was performed. Insulin resistance was calculated by using the homeostasis model assessment of insulin resistance index (HOMA-IR). Plasma ADM levels were measured by high performance liquid chromatographic (HPLC) method. Plasma ADM, fasting insulin levels and HOMA-IR were significantly higher in patients with PCOS than the control group. ADM levels were positively correlated with insulin levels and HOMA-IR index. The best cut-off value of ADM levels to identify the presence of insulin resistance (HOMA-IR≥2.7) was 30.44 ng/ml. Calculated odds ratio of insulin resistance by using logistic regression analysis, as predicted by ADM, was 0.15 (95% confidence interval, 0.037-0.628; p=0.009). In multiple regression analysis, ADM level was an independent predictor of HOMA-IR index. Our finding indicated that ADM levels increased in women with PCOS in accordance with HOMA-IR. ADM could be a significant independent determinant of insulin resistance in women with PCOS.

Peripheral Administration of Human Adrenomedullin and Its Binding Protein Attenuates Stroke-Induced Apoptosis and Brain Injury in Rats

Stroke is a leading cause of death and the primary medical cause of acquired adult disability worldwide. The progressive brain injury after acute stroke is partly mediated by ischemia-elicited inflammatory responses. The vasoactive hormone adrenomedullin (AM), upregulated under various inflammatory conditions, counterbalances inflammatory responses. However, regulation of AM activity in ischemic stroke remains largely unknown. Recent studies have demonstrated the presence of a specific AM binding protein (that is, AMBP-1) in mammalian blood. AMBP-1 potentiates AM biological activities. Using a rat model of focal cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO), we found that plasma levels of AM increased significantly, whereas plasma levels of AMBP-1 decreased significantly after stroke. When given peripherally early after MCAO, exogenous human AM in combination with human AMBP-1 reduced brain infarct volume 24 and 72 h after MCAO, an effect not observed after the treatment by human AM or human AMBP-1 alone. Furthermore, treatment of human AM/AMBP-1 reduced neuron apoptosis and morphological damage, inhibited neutrophil infiltration in the brain and decreased serum levels of S100B and lactate. Thus, human AM/AMBP-1 has the ability to reduce stroke-induced brain injury in rats. AM/AMBP-1 can be developed as a novel therapeutic agent for patients with ischemic stroke.

A spontaneous, double-blind, double-dummy cross-over study on the effects of daily vardenafil on arterial stiffness in patients with vasculogenic erectile dysfunction

BackgroundIt is known that the incidence of endothelial dysfunction in patients with vascular erectile dysfunction (ED) is increased. The effects of daily vardenafil on endothelial function and arterial stiffness in patients with erectile dysfunction (ED) have never been investigated. Methods20 men complaining vascular ED (mean IIEF5=12±6 and peak systolic velocity-PSV=24±2cm/s) were enrolled in a 4-week, randomized, double-blind, double-dummy, crossover study (mean age 59±11) and received either vardenafil 10mg daily or 20mg on-demand with a two-week washout interval. Primary endpoints were variation from baseline of reactive hyperemia (RH) and augmentation index (AI) calculated by fingertip peripheral arterial tonometry (PAT) device. Secondary endpoints were variations of IIEF-5 and SEP3 scores from baseline and plasma surrogate markers of endothelial function, i.e. endothelin-1 (ET-1) and adrenomedullin (ADM). ResultsPatients who took daily vardenafil (vs. on-demand) reported significant (P<0.01) improvements in arterial stiffness as evaluated by AI and reduction of plasma ADM levels (p<0.05) but no improvement in average RH. When corrected for heart rate, ADM showed a strong direct relationship with AI (r2=0.22; p<0.005). The proportion of patients with an IIEF5 score of ≥22 or in SEP3 percentage of success rates were similar. Each treatment resulted in significantly greater IIEF5 scores (p<0.001) and better SEP3 response rates (p<0.0001) compared with baseline. ConclusionsWe demonstrated that daily vardenafil improves arterial stiffness and erectile function measurements in men with severe vasculogenic ED. This effect may be mediated, at least in part, by a reduction in ADM circulating levels.

Relationship of increased circulating adrenomedullin with cardiac dysfunction, inflammation, oxidative stress and volume overload in hemodialysis patients

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis. The aim of our study was to investigate whether circulating AM might be related to cardiac function, volume overload, oxidative stress and inflammation in hemodialysis patients. Plasma adrenomedullin, C-reactive protein (CRP), oxidized LDL (ox-LDL), lipoprotein (a), systolic and diastolic cardiac functions were assessed before hemodialysis in 80 patients as well as in 40 healthy control subjects. Plasma adrenomedullin levels were significantly higher in the hemodialysis group compared to the control group. Plasma adrenomedullin levels were negatively correlated with systolic and diastolic blood pressure, S/D ratio, deceleration time, left ventricular ejection fraction, ox-LDL and lipoprotein (a). However, it was positively correlated with CRP, delta body weight, mitral E/A wave, and inferior vena cava diameter. Higher plasma adrenomedullin levels may provide a possible index of cardiac dysfunction, systemic inflammation, and volume overload conditions in haemodialysis patients with concomitant cardiovascular disease. In addition, the negative correlation between ox-LDL, lipoprotein (a) and adrenomedullin may suggest that endogenous AM is an important protective factor in anti-atherosclerosis and might be useful as a new target for prevention and therapy for the disease.

Role of uterine artery Doppler velocimetry indices and plasma adrenomedullin level in women with unexplained recurrent pregnancy loss

To evaluate uterine artery Doppler flow resistance and plasma adrenomedullin levels in women with unexplained recurrent pregnancy loss (RPL) compared to controls. Eighty-three women, who attend the department of Obstetrics and Gynecology, Benha University, Egypt, participated in this study (RPL group: n=40, and control group: n=43). Uterine artery Doppler and plasma adrenomedullin (AM) (pg/mL) levels were measured for all women in the mid-luteal phase of a non-pregnant cycle. Both uterine artery pulsatility index (PI) and AM levels were significantly higher in RPL group compared to controls (2.71 ± 0.259 vs 2.06 ± 0.194 for PI and 287.5 ± 80.4 pg/mL vs 156.1 ± 39.8 pg/mL for AM, P<0.01). Uterine artery PI had a significant positive correlation with plasma AM levels both in the RPL group (r=0.645, P<0.001) and in the control group (r=0.384, P=0.011). Number of previous miscarriages in RPL group was significantly correlated with both uterine artery PI (r=0.838, P=0.015) and plasma AM levels (r=0.509, P=0.001). Uterine artery PI may be useful in identifying women with unexplained RPL who have impaired uterine circulation. Plasma AM may serve as a biochemical marker for RPL caused by impaired uterine perfusion.

Adrenomedullin and calcitonin gene-related peptide receptors in endocrine-related cancers: opportunities and challenges

Adrenomedullin (AM), adrenomedullin 2 (AM2/intermedin) and calcitonin gene-related peptide (CGRP) are members of the calcitonin family of peptides. They can act as growth or survival factors for a number of tumours, including those that are endocrine-related. One mechanism through which this occurs is stimulating angiogenesis and lymphangiogenesis. AM is expressed by numerous tumour types and for some cancers, plasma AM levels can be correlated with the severity of the disease. In cancer models, lowering AM content or blocking AM receptors can reduce tumour mass. AM receptors are complexes formed between a seven transmembrane protein, calcitonin receptor-like receptor and one of the two accessory proteins, receptor activity-modifying proteins (RAMPs) 2 or 3 to give the AM1 and AM2 receptors respectively. AM also has affinity at the CGRP receptor, which uses RAMP1. Unfortunately, due to a lack of selective pharmacological tools or antibodies to distinguish AM and CGRP receptors, the precise receptors and signal transduction pathways used by the peptides are often uncertain. Two other membrane proteins, RDC1 and L1/G10D (the 'ADMR'), are not currently considered to be genuine CGRP or AM receptors. In order to properly evaluate whether AM or CGRP receptor inhibition has a role in cancer therapy, it is important to identify which receptors mediate the effects of these peptides. To effectively distinguish AM1 and AM2 receptors, selective receptor antagonists need to be developed. The development of specific CGRP receptor antagonists suggests that this is now feasible.

Adrenomedullin in the Rat Ovary: Its Production, Interaction with Endothelin 1, and Actions on Progesterone Secretion During Gestation.

Adrenomedullin (ADM), a novel vasorelaxant peptide, was found in human/rat ovaries and uteri. Plasma ADM level increases in pregnant women and pregnant rats. Our previous study in Sprague-Dawley rats showed that large antral follicles (diameter above 900 µm) and newly formed corpus luteum (CL) expressed higher levels of Adm and one of its receptor activity-modifying protein (Ramp2) than small antral follicles (diameter of 200-400 µm). EDN is luteolytic and is known to inhibit progesterone production. The aims of this study was to study the interaction of ADM and endothelin 1 (EDN1) in follicles and newly formed CL and the action of ADM on progesterone production in CL during pregnancy. Adult Sprague-Dawley rats were induced to ovulate by administration of eCG followed by hCG injection. Isolated large follicles were incubated with ADM/EDN1 for 6 h; newly formed corpora lutea were also incubated with ADM/EDN1 for 6 h with/without hCG. For the effects of EDN1, the gene expression of Adm and its receptor components in the large antral follicles and CL were measured by real-time RT-PCR. For the effects of ADM, the gene expression of Edn1 and endothelin receptor B (Ednrb) was measured. The effects of the ADM and CGRP receptor antagonists (hADM22-25 and hCGRP8-37) were also tested. CL were isolated from early (7-day), mid (12-day), and late (17-day) pregnant rats and were incubated for 6 h with ADM with or without an ADM or a receptor antagonist. Progesterone secretion from CL was measured by Enzyme Immunoassay. EDN1 was found to reduce the gene expression of Adm and Ramp1 in large antral follicles after 6 h incubation with ADM. ADM treatment upregulated Edn1 expression levels in large antral follicles. EDN1 also reduced the gene expression of Adm in the CL with/without hCG. ADM treatment increased Edn1 expression. In the presence of hCG, ADM treatment increased both Edn1 and also Ednrb expression. ADM suppressed progesterone production from the CL in early and late pregnancy while enhancing progesterone production in mid-pregnancy, which correlated well with the greater progesterone production at mid-pregnancy. The effects of ADM on Edn1 gene expression and progesterone production were blocked by the CGRP receptor antagonist. One of the roles of ADM in CL during pregnancy might be the regulation of progesterone production and this may be achieved via the interaction with END1. Acknowledgement: This work was substantially supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (HKU7736/07M). (poster)

Plasma adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients diagnosed as having early rheumatoid arthritis

The aim of this study was to investigate plasma adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) level in patients diagnosed with early rheumatoid arthritis (RA). Furthermore, several inflammatory cytokines were measured in those patients to clarify the roles of AM and PAMP. Forty patients diagnosed with early RA (women 46 ± 8.5 years old) and 10 healthy controls (women 57 ± 5 years old) were studied. Plasma levels of AM, PAMP, matrix metalloprotease 3 (MMP-3), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) were measured using an immunoradiometric assay and enzyme-linked immunosorbent asay (ELISA) methods. The plasma levels of AM (17.5 ± 8.4 fmol/ml) and PAMP (2.01 ± 0.57 fmol/ml) in patients exceeded those in healthy controls (AM 8.6 ± 1.7, PAMP 1.17 ± 0.34 fmol/ml). Moreover, plasma AM and PAMP levels demonstrated a significantly positive correlation with plasma MMP-3 and IL-6 levels. Nevertheless, CRP and TNF-α levels in these patients showed no significant correlation with plasma AM and PAMP levels. These data support the possible role for AM and PAMP in the pathophysiology of early RA.

Plasma adrenomedullin and proadrenomedullin N-terminal 20 peptide in patients diagnosed as having early rheumatoid arthritis

The aim of this study was to investigate plasma adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) level in patients diagnosed with early rheumatoid arthritis (RA). Furthermore, several inflammatory cytokines were measured in those patients to clarify the roles of AM and PAMP. Forty patients diagnosed with early RA (women 46 +/- 8.5 years old) and 10 healthy controls (women 57 +/- 5 years old) were studied. Plasma levels of AM, PAMP, matrix metalloprotease 3 (MMP-3), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and C-reactive protein (CRP) were measured using an immunoradiometric assay and enzyme-linked immunosorbent asay (ELISA) methods. The plasma levels of AM (17.5 +/- 8.4 fmol/ml) and PAMP (2.01 +/- 0.57 fmol/ml) in patients exceeded those in healthy controls (AM 8.6 +/- 1.7, PAMP 1.17 +/- 0.34 fmol/ml). Moreover, plasma AM and PAMP levels demonstrated a significantly positive correlation with plasma MMP-3 and IL-6 levels. Nevertheless, CRP and TNF-alpha levels in these patients showed no significant correlation with plasma AM and PAMP levels. These data support the possible role for AM and PAMP in the pathophysiology of early RA.

Hemodynamic effects of chronic smoking in liver cirrhosis: a role for adrenomedullin

To evaluate the effect of smoking on the hemodynamic status of liver cirrhosis and several vasoactive substances. Hemodynamic, blood gases values, liver parameters, and several vasopressors and vasodilators substances were measured in consecutive inpatients diagnosed of liver cirrhosis divided into two groups: smokers and nonsmokers. Nineteen smoking cirrhotic patients and 13 nonsmoking cirrhotic patients were studied. Both groups showed similar age, Child--Pugh and model for end-stage liver disease indexes. Smokers had higher levels of hemoglobin and lower partial pressure of arterial oxygen, FEV1/FVC %, cardiac output and total vascular resistance than nonsmokers. Plasma level of adrenomedullin was independently higher in nonsmoking cirrhotic patients than in smokers. In contrast with smoking cirrhotic patients, nonsmoking cirrhotic patients show an increased systemic vasodilation, which could depend on higher plasmatic levels of adrenomedullin.

Attenuation of Renal Ischemia and Reperfusion Injury by Human Adrenomedullin and its Binding Protein

Acute renal failure secondary to ischemia and reperfusion (I/R) injury poses a significant burden on both surgeons and patients. It carries a high morbidity and mortality rate and no specific treatment currently exists. Major causes of renal I/R injury include trauma, sepsis, hypoperfusion, and various surgical procedures. We have demonstrated that adrenomedullin (AM), a novel vasoactive peptide, combined with AM binding protein-1 (AMBP-1), which augments the activity of AM, is beneficial in various disease conditions. However, it remains unknown whether human AM/AMBP-1 provides any beneficial effects in renal I/R injury. The objective of our study therefore was to determine whether administration of human AM/AMBP-1 can prevent and/or minimize damage in a rat model of renal I/R injury. Male adult rats were subjected to renal I/R injury by bilateral renal pedicle clamping with microvascular clips for 60 min followed by reperfusion. Human AM (12 microg/kg BW) and human AMBP-1 (40 microg/kg BW) or vehicle (52 microg/kg BW human albumin) were given intravenously over 30 min immediately following the clip removal (i.e., reperfusion). Rats were allowed to recover for 24 h post-treatment, and blood and renal tissue samples were collected. Plasma levels of AM were measured using a radioimmunoassay specific for rat AM. Plasma AMBP-1 was measured by Western analysis. Renal water content and serum levels of systemic markers of tissue injury were measured. Serum and renal TNF-alpha levels were also assessed. At 24 h after renal I/R injury, plasma levels of AM were significantly increased while plasma AMBP-1 was markedly decreased. Renal water content and systemic markers of tissue injury (e.g., creatinine, BUN, AST, and ALT) were significantly increased following renal I/R injury. Serum and renal TNF-alpha levels were also increased post injury. Administration of human AM/AMBP-1 decreased renal water content, and plasma levels of creatinine, BUN, AST, and ALT. Serum and renal TNF-alpha levels were also significantly decreased after AM/AMBP-1 treatment. Treatment with human AM/AMBP-1 in renal I/R injury significantly attenuated organ injury and the inflammatory response. Thus, human AM combined with human AMBP-1 may be developed as a novel treatment for patients with acute renal I/R injury.

Adrenomedullin Plasma Levels Predict Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy

Increase in adrenomedullin (ADM) plasma levels in congestive heart failure (HF) patients is due to many cardiac and systemic factors, particularly to greater fluid retention and to activation of sympathetic nervous system. Aim of this study was to assess the role of plasma ADM levels in HF patients treated by cardiac resynchronization therapy (CRT). 50 patients, mean age 70 years, 34 male, New York Heart Association (NYHA) Class III-IV HF, left ventricular ejection fraction (LVEF) < 35%, underwent CRT. All patients were in sinus rhythm and with complete left bundle branch block (QRS duration 138 +/- 6 msec). A complete echoDoppler exam, blood samples for brain natriuretic peptide (BNP), and ADM were obtained from 2 to 7 days before implantation. At 16 +/- 6 months follow-up, >or=1 NYHA Class improvement was observed in 38 patients. However, a >10% reduction in end-systolic dimensions (ESD) was reported in 21 patients (Group I): -16.6 +/- 1.8%; in the remaining 29 patients ESD change was almost negligible: -2.0 +/- 1.03% (Group II), P < 0.0001. The two groups were comparable for age, sex, cause of LV dysfunction, therapy, QRS duration at baseline, preimplantation ESD, LVEF%, and BNP. Significantly higher pre implantation ADM levels were present in Group I than in Group II (27.2 +/- 1.8 pmol/l vs 17.9 +/- 1.4, P = 0.0003). Significantly higher ADM levels indicate a subgroup of patients in whom reverse remodeling can be observed after CRT. Patients with lower ADM basal values before CRT could represent a group in whom the dysfunction is so advanced that no improvement can be expected.

Plasma Adrenomedullin level in Egyptian children and Adolescents with type 1 diabetes mellitus: relationship to microvascular complications

BackgroundAdrenomedullin (AM) is known to be elevated in different clinical situations including diabetes mellitus (DM), but its potential role in the pathogenesis of vascular complications in diabetic children and adolescents is to be clarified. Hence, the study aimed at assessment of plasma adrenomedullin levels in children and adolescents with type 1 DM and correlation of these levels with metabolic control and diabetic microvascular complications (MVC).MethodsThe study was performed in the Diabetes Specialized Clinic, Children's Hospital of Ain Shams University in Cairo, Egypt. It included 55 diabetic children and adolescents (mean age 13.93 ± 3.15 years) who were subdivided into 40 with no MVC and 15 with MVC. Thirty healthy subjects, age-and sex- matched were included as control group (mean age 12.83 ± 2.82 years). Patients and controls were assessed for glycosylated hemoglobin (HbA1c) and plasma adrenomedullin assay using ELISA technique.ResultsMean plasma AM levels were significantly increased in patients with and without MVC compared to control group, (110.6 pg/mL, 60.25 pg/mL and 39.2 pg/mL respectively) (P < 0.01) with higher levels in those with MVC (P < 0.05). Plasma AM levels were positively correlated with both duration of diabetes (ρ = 0.703, P < 0.001) and glycemic control (HbA1c) (ρ = 0.453, P < 0.001).ConclusionHigher plasma AM levels in diabetics particularly in those with MVC & its correlation with diabetes duration and metabolic control may reflect the role of AM in diabetic vasculopathy in the pediatric age group.

Human adrenomedullin and its binding protein ameliorate sepsis-induced organ injury and mortality in jaundiced rats

Sepsis is a serious complication for patients with obstructive jaundice. Although administration of adrenomedullin (AM) in combination with its binding protein (AMBP-1) is protective after injury, it remains unknown whether AM/AMBP-1 ameliorates sepsis-induced organ injury and mortality in the setting of biliary obstruction. The aim of this study is, therefore, to test the efficacy of human AM/AMBP-1 in a rat model of obstructive jaundice and polymicrobial sepsis. To study this, obstructive jaundice was induced in male adult rats (275–325 g) by common bile duct ligation (BDL). One week after BDL, the rats were subjected to sepsis by cecal ligation and puncture (CLP). Plasma levels of AM and AMBP-1 were measured at 20 h after CLP. In additional groups of BDL + CLP rats, human AM/AMBP-1 (24/80 μg/kg body weight (BW)) or vehicle (i.e., human albumin) was administered intravenously at 5 h after CLP. Blood and tissue samples were collected at 20 h after CLP for various measurements. To determine the long-term effect of human AM/AMBP-1 after BDL + CLP, the gangrenous cecum was removed at 20 h after CLP and 7-day survival was recorded. Our results showed that plasma levels of AM were significantly increased while AMBP-1 levels were markedly decreased after BDL + CLP ( n = 8, P < 0.05). Administration of human AM/AMBP-1 attenuated tissue injury and inflammatory responses after BDL + CLP. Moreover, human AM/AMBP-1 significantly increased the survival rate from 21% ( n = 14) to 53% ( n = 15). Thus, human AM/AMBP-1 ameliorates sepsis-induced organ injury and mortality in jaundiced rats. Human AM/AMBP-1 can be further developed as a novel treatment for sepsis in jaundiced patients.

Plasma Adrenomedullin Levels during Multiple Pregnancy

Background: To estimate the normal level of adrenomedullin (AM) during multiple pregnancy. Methods: The study population consisted of 5 women with normal cycles, 130 women with normal pregnancy between 6 and 40 weeks of gestation, 93 women with twin pregnancy and 42 women with triplet pregnancy. Results: Total AM concentration in the first trimester (13.7 ± 0.58 fmol/ml), second trimester (26.8 ± 1.13 fmol/ml) and third trimester (37.8 ± 1.32 fmol/ml) in pregnant women was significantly higher than that in nonpregnant women (8.0 ± 0.71 fmol/ml). In each trimester, the maternal plasma concentrations of triplet-pregnant women were significantly higher than in twin and singleton-pregnant women. Umbilical venous AM levels (29.9 ± 2.63 fmol/ml) were higher than umbilical arterial AM (20.2 ± 2.04 fmol/ml). Conclusion: Since alterations in the AM concentration in maternal plasma may mediate compensatory vascular responses in the uterine circulation, it might be useful to know the normal level of AM during multiple pregnancy in order to detect abnormalities during multiple pregnancy.

Adrenomedullin in patients with type 2 diabetes and kidney disease

Secreting vasoactive factors such asadrenomedullin (AM) has been intensivelyinvestigated due to its vascular protective propertiesand promising potential as a therapeutic target. Therelationship between adrenomedullin and type (2)diabetes needs to be elucidated as it is associatedwith significant elevation in plasma adrenomedullinlevels. The aim of this study was to evaluate therole of adrenomedullin in the development ofvasculopathy and its significance as a markerdenoting renal affection in type 2 diabetic patients. Materials and Methods: This study was conductedon 60 diabetic patients, 20 without nephropathy, 20with nephropathy & 20 with diabetic nephropathy(DN) on haemodialysis as well as 20 age- and sex matchedhealthy controls. All were subjected to fullhistory, Echocardiography, lipid profile analysisand plasma adrenomedullin using ELISA method. Results: plasma AM concentration was elevated inall groups of diabetic patients and increment wasdependent on the severity of DN (P<0.0001,P<0.0001, P<0.0001 respectively). There werepositive correlation between adrenomedullin andleft ventricular internal dimensions both in diastole& systole (P<0.001, P<0.005) and negativecorrelation between AM and ejection fraction (EF)P<0.0001. There was positive correlation betweenadrenomedullin and cholesterol, triglycerides andLDL (p<0.002, p<0.001and p<0.003 respectively)and a negative correlation with HDL (P<0.004). Conclusion: Adrenomedullin is supposed to play arole in the pathogenesis of diabeticmicrovasculopathy in renal patients. So it can beused to identify high-risk subjects and modulatingits action would have therapeutic potential in the prevention of diabetic nephropathy.

The Changes of Plasma Malondialdehyde, Nitric Oxide, and Adrenomedullin Levels in Patients with Preeclampsia

Objective. The aim of the study was to investigate the role of malondialdehyde, nitric oxide and adrenomedullin in the etiopathogenesis of preeclampsia. Material and Methods. Forty-two pregnant women with preeclampsia and 30 healthy pregnant women were involved. The plasma concentrations of malondialdehyde, nitric oxide, and adrenomedullin were compared between the study group and the control group. Results. In women with preeclampsia the plasma concentrations of malondialdehyde was higher while nitric oxide and adrenomedullin concentrations were lower compared to control subjects. Conclusion. We concluded that the plasma levels of ADM and NO are decreased while MDA levels are increased in subjects with preeclampsia and that might contribute to the pathophysiology of preeclampsia through the lack of a paracrine vasodilatory effect on uteroplacental blood flow.