Adrenomedullin has a role in angiogenic effects of resveratrol in adipose tissues of obese female rats.

Obesity is a complex, chronic disease that arises according to the interaction between genetic and environmental factors. The expansion and growth of white adipose tissue (WAT) could be related to angiogenesis. Resveratrol and adrenomedullin (AdM) were used for the inhibition of angiogenesis in metabolically passive WAT for inhibiting the expansion of this tissue, and the activation of angiogenesis in metabolically active brown adipose tissue (BAT) for increasing daily energy consumption as a way of reducing obesity. Rats were divided into eight groups. Four obese groups were fed with a high-fat diet containing 60% fat as energy for three months. After obtaining obesity, 2.5 nmol/kg AdM and 10 mg/kg resveratrol were treated to experiment groups intraperitoneally (i.p.) every other day for four weeks. AdM and vascular endothelial growth factor A (VEGF-A) mRNA levels were detected with semi-quantitative PCR; protein levels were detected with Western Blotting. AdM and resveratrol are multifactorial molecules, thus, this study has revealed a few novel evidence. The results were distinct in the group and treatment levels. The results showed that resveratrol has a role in angiogenesis in obesity and contributed to AdM production. It is observed that AdM has regulated its expression and increased the effect of resveratrol in WAT. AdM and VEGF-A gene expressions could not be detected in BAT; however, it is suggested that resveratrol may have a pro-angiogenic effect in BAT of obese rats according to the protein levels. AdM also has regulated VEGF-A level according to the metabolic situation of the organism.

Adrenomedullin reduces antioxidant defense system and enhances kidney tissue damage in cadmium and lead exposed rats.

Adrenomedullin (AdM) is synthesized and secreted by a number of cells and tissue. AdM is a potent vasodilator but it is also considered a neuromodulator, an angiogenic factor, and a hormone regulator. AdM possess antiapoptotic, antioxidant, and antimicrobial properties. Heavy metals such as cadmium and lead are found widely in the environment and they have important biological functions. Lead (Pb) and cadmium (Cd) can accumulate in the lungs, liver, bone, and kidneys and cause serious organ damage. In the present study, we investigated the effect of AdM, Pb + AdM, and Cd + AdM treatments on superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as the level of malondialdehyde (MDA) in the kidney. Heavy metal accumulation was determined in kidney with and without AdM infusion and kidney damage was evaluated by light and electron microscopy. Increased heavy metal accumulation was observed in the heavy metal and AdM treated groups. SOD, CAT, GSH-Px activities, and MDA levels were significantly different in the treatment groups when compared with the control group. Tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles were observed in the kidney following treatment. Therefore, AdM infusion has no beneficial and/or compensatory role in cadmium and lead toxicity in the kidney. We conclude that heavy metal accumulation in the kidney in conjunction with AdM infusion is cytotoxic despite the known beneficial effects of adrenomedullin.

Circulating adrenomedullin levels in ankylosing spondylitis and Familial Mediterranean Fever.

INTRODUCTION: Adrenomedullin (AM) is a 52-amino acid peptide with vasorelaxant properties. Apart from its roles on vascular tonus, AM can also contribute to inflammatory events. Plasma AM levels were elevated in connective tissue diseases and vasculitic disorders. Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine initiating in the sacroiliac joints. Familial Mediterranean Fever (FMF) is a hereditary disorder characterized by self-limiting acute attacks of fever and the presence of sustained subclinical inflammation in the attack-free periods. In this study, we investigated plasma AM levels in patients with AS and patients with FMF. METHODS: Twenty AS patients with active disease manifestations (mean age: 41.6+/-10.9 years, female/male: 7/13), 28 FMF patients with acute attack (mean age: 27.4+/-10.7 years, female/male: 17/11), and 26 healthy controls (mean age: 39.9+/-5.5 years, female/male: 16/10) were enrolled in this study. AM levels were also measured in 11 FMF patients 2 months after the cessation of their attacks. AM levels of those 11 patients during their FMF attacks and attack-free periods were also compared. RESULTS: Median plasma AM levels were 23.86 (17.24-40.09) pmol/mL, 27.33 (17.24-38.52) pmol/mL, and 26.11 (17.05-37.42) pmol/mL in AS patients, FMF patients with acute attack, and healthy controls, respectively (p>0.05). AM levels were also similar in the attack-free periods of FMF patients [26.35 (24.35-34.14) pmol/mL]. There was no correlation between plasma AM levels and C-reactive protein, or between plasma AM levels and erythrocyte sedimentation rate. CONCLUSIONS: AM does not seem to have any role in the pathogenesis of AS and FMF. Previous reports of elevated levels of AM in connective tissue disorders and vasculitic diseases are probably disease specific, and AM does not seem to be a common component of inflammatory rheumatic disorders.

The effect of adrenomedullin on rats exposed to lead.

Adrenomedullin (AdM) was originally discovered as a vasorelaxant peptide. The antioxidative properties of AdM have been reported recently. Through its antioxidative effect, adrenomedullin can protect organs from damage induced by stressors. Lead, commonly detected in air, soil, water and food, is a major source of oxidative stress. The effect of AdM in the liver of rats exposed to lead was investigated. Twenty-four female Wistar rats were divided into four groups: a control group (C), adrenomedullin group (AdM), lead (Pb) group and lead + adrenomedullin (Pb + AdM) group. In the Pb-treated groups, the animals were exposed to lead in drinking water containing 250 ppm PbCl2 for 4 weeks. In the AdM-treated group, the animals received an i.p. injection of AdM (3000 ng kg(-1) body weight) in the third week of lead treatment for 1 week. The activities of catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were determined in the liver of rats. Histological changes in the liver were examined by light and electron microscopy as well. The MDA levels were increased significantly in the Pb-treated groups, but in the Pb + AdM group the MDA levels were decreased significantly when compared with the Pb group. AdM reduced hepatic damage in the Pb + AdM group, but the difference in the total histopathological scores between the Pb and Pb + AdM groups was not significant. When the results are taken together, it can be concluded that AdM may have protective or compensating effects in lead toxicity.

Maternal and umbilical venous adrenomedullin and nitric oxide levels in intrauterine growth restriction.

OBJECTIVE: To verify whether adrenomedullin (AM) and nitric oxide (NO) concentrations are changed in the maternal and fetal circulation in pregnancies complicated by intrauterine growth restriction (IUGR) compared to normal pregnancies, and to determine any relationship between them. METHODS: Forty-six small for gestational age (SGA) and 34 appropriate for gestational age (AGA) infants were included in the study. Umbilical and maternal venous AM and NO concentrations were determined. RESULTS: Umbilical NO concentrations in SGA infants (mean +/- SD; 176.2 +/- 75.8 micromol/L) were significantly greater than in AGA infants (143.4 +/- 39.2 micromol/L) (p = 0.015). However, umbilical AM concentrations were similar in SGA and AGA infants with 14.2 +/- 4.4 pmol/mL and 14.5 +/- 6.2 pmol/mL, respectively (p > 0.05). There was no relationship between NO and AM levels in umbilical blood (r = 0.09, p = 0.40). No difference was found between either AM or NO levels in the maternal plasma of the two groups. CONCLUSIONS: We suggest that NO is increased in the fetoplacental circulation in SGA infants probably as a response to decreased blood flow, whereas AM is not. Additionally, increased NO in the fetoplacental circulation was found to be independent from AM secretion.

Increased levels of nitric oxide, cortisol and adrenomedullin in patients with chronic schizophrenia.

OBJECTIVE: To investigate the levels of serum cortisol, dehydroepiandrosterone sulfate (DHEA-S), nitric oxide (NO) and adrenomedullin (AM) in schizophrenic patients. SUBJECTS AND METHODS: Sixty-six male patients with chronic schizophrenia and 28 normal male subjects participated in this study. The duration of disease was 145 +/- 120 (mean +/- SD) months. Serum levels of cortisol and DHEA-S were measured by electrochemiluminescence; plasma nitrite levels as an index of NO were measured with the Griess reaction, while plasma AM concentration was measured by using high-performance liquid chromatography. RESULTS: Patients (12.48 +/- 3.2 microg/dl), as compared to controls (10.31 +/- 3.1 microg/dl), had higher levels of baseline cortisol (p < 0.05). DHEA-S levels were lower in patients though this did not reach statistical significance (302 +/- 156 microg/dl compared to control, 322 +/- 96 microg/dl, p > 0.05). The mean levels of plasma AM and NO in the schizophrenic group (44.33 +/- 5.07 pmol/l and 36.27 +/- 17.6 micromol/l) were significantly higher than the levels in the control group (14.56 +/- 4.03 pmol/l and 32.54 +/- 7.14 micromol/l; p < 0.001, p < 0.03, respectively). There was a positive association between duration of disease and cortisol/DHEA-S ratio and cortisol level. CONCLUSION: The data show that schizophrenia is associated with abnormal levels of cortisol, DHEA-S, NO and AM.

Adrenomedullin fails to reduce cadmium-induced oxidative damage in rat liver.

Recent studies have demonstrated that chronic cadmium administration induces oxidative stress. In the present study, we investigated the possible therapeutic effect of adrenomedullin, a potent antioxidant, in cadmium-induced morphological, ultrastructural and biochemical alterations. Two groups of rats were exposed to 100 ppm of CdCl(2) in drinking water for four weeks. One of these groups received 3000 ng/kg body weight of adrenomedullin (AdM) intraperitoneally during the last week. Hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides and changes in the antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPx) and glutathione reductase (GSH) levels. Hepatic damage score was significantly higher in Cd-administered rats than those of controls (p<0.005). Cd-induced ultrastructural changes in hepatocytes included focal parenchymal cell necrosis, dilatation of rough endoplasmic reticulum, proliferation of lysosomes and mitochondrial degeneration. Hepatic damage was accompanied by significant increase in tissue MDA level (p<0.05) and significant decrease in tissue GSH level (p<0.05), and SOD and GPx activities (p>0.05, p>0.005, respectively). Adrenomedullin failed to restore the light and electron microscopic, and biochemical changes. We conclude that although we administered a high dose of adrenomedullin, it failed to reduce cadmium-induced hepatic damage probably because of the irreversibility of Cd-induced hepatic injury.

The effects of anticancer drugs on levels of nitric oxide and adrenomedullin.

Nephrotoxicity is one of the most important complications of anticancer treatment. Ifosfamide, platinum and methotrexate (MTX) affect renal tubular epithelial cells. Nitric oxide (NO) serves many functions within the kidney. Adrenomedullin (AM) is a potent vasodilator peptide, and may function as a circulating hormone and an autocrine/paracrine mediator involved in the regulation of the cardiovascular system, blood pressure, and renal function. It also has a renoprotective effect and inhibits the generation of reactive oxygen metabolites. To our knowledge, no studies have investigated the effects of anticancer drugs on levels of AM and NO. We investigated the effects of these drugs on the levels of AM and total nitrite, a stable product of NO, and their relations to renal functions. The study was performed in 18 patients (13 males, 5 females) who received chemotherapeutic regimens including high-dose MTX or ifosfamide and platinum. Total nitrite was quantitated by means of the Griess reaction, while AM level was measured by high performance liquid chromatography (HPLC). Plasma total nitrite level (micromol/L) was decreased after chemotherapy (78.73 +/- 47.28 vs. 46.69 +/- 13.89, p: 0.002). A statistically significant difference was found between fractional excretion (FE) of total nitric oxide (FE(NO)) before and after chemotherapy (25.89 +/- 23.11 vs. 51.74 +/- 40.01, p: 0.008). The differences in plasma AM levels (pmol/ml) before (25.07 +/- 4.98) and after (30.20 +/- 1.39) chemotherapy were also statistically significant (p: 0.005). FE(AM) after chemotherapy (1.41 +/- 1.01) was found to be higher than before chemotherapy (0.64 +/- 0.43) (p: 0.000). Our results indicate that some chemotherapeutic agents (high-dose MTX, ifosfamide, and cisplatinium) may cause renal tubular damage. FE(AM) and FE(NO) may also be used for the detection of subclinical acute tubular nephrotoxicity. However, further detailed researches will be necessary to establish the certain role of NO and AM in toxicities of chemotherapeutic agents.

Protective role of caffeic acid phenethyl ester in the liver of rats exposed to cold stress.

Cold exposure can induce a form of environmental stress. Cold stress (CS) alters homeostasis, results in the creation of reactive oxygen species and leads to alterations in the antioxidant defense system. The caffeic acid phenethyl ester (CAPE), an active component of propolis, has an antioxidant capacity. We investigated the effect of CS on oxidative stress and antioxidant defense system and the possible protective effect of CAPE in rat liver tissue. Twenty-four female Wistar Albino rats were divided into four groups: Control, CAPE-treated, CS, and CAPE-treated CS (CS + CAPE) group. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and total glutathione (GSH) and malondialdehyde (MDA) levels were measured. In addition, histological changes in liver tissue were examined by light microscopy. SOD, CAT and GSH-Px activities and total GSH level were significantly declined in the CS group. In the CS + CAPE group, the activities of these three enzymes and GSH level significantly raised with regard to the CS group. MDA levels increased in the CS group and decreased in the CS + CAPE group. The tissues of the CS group showed some histopathological changes such as necrosis, hepatocyte degeneration, sinusoidal dilatation, hemorrhage and vascular congestion and dilatation. In the CS + CAPE group, the histopathological evidence of hepatic damage was markedly reduced. Histological parameters were consistent with biochemical parameters. In this study, CS increased oxidative stress in liver tissue. CAPE regulated antioxidant enzymes, inhibited lipid peroxidation and reduced hepatic damage.

Adrenomedullin and total nitrite levels in children with familial Mediterranean fever.

AIM: Familial Mediterranean fever (FMF) is the most frequent periodic syndrome characterised by recurrent attacks of polyserositis. However, recent studies revealed that there might be an ongoing subclinical inflammation between the attacks. As nitric oxide (NO) and adrenomedullin (AM) are both synthesised in the endothelium, and mediates many functions within immune system, we considered them to be an interesting target of investigation in FMF. METHODS: Fifteen children with FMF receiving regular colchicine, ranging in age from 3 to 16 years, were investigated in comparison with 15 healthy age- and sex-matched controls. The mean age of the patients was 9.7 +/- 3.9 years. Total nitrite, a stable product of NO, was quantitated by means of the Griess reaction, while AM was measured by HPLC. RESULTS: Plasma-urinary AM and total nitrite levels were significantly higher in children with FMF. Plasma AM levels (pmol/mL) in patients and controls were 40.95 +/- 5.99 vs. 34.86 +/- 5.24, P < 0.05, and urinary AM excretion (pmol/mg creatinine) was 51.16 +/- 28.15 vs. 37.5 +/- 24.26, P < 0.05 respectively. Plasma total nitrite levels (micromol/L) in patients and controls were 44.80 +/- 10.36 vs. 32.13 +/- 9.28, P < 0.05, and urinary nitrite excretion (micromol/mg creatinine) was 2.24 +/- 1.71 vs. 1.09 +/- 0.96, P < 0.05 respectively. CONCLUSION: This study considered that AM and NO may have a role in the immuno-inflammatory process of FMF, although, whether these act to preserve, or protect against, further inflammatory injury is not clear. Our results further supports the hypothesis that these patients have subclinical inflammation between attacks.

The effects of carbon dioxide pneumoperitoneum on tyrosine hydroxylase activity.

PURPOSE: The aim of this study is to investigate the effects of carbon dioxide (CO2) pneumoperitoneum on tyrosine hydroxylase (TH) activity and total protein (TP) levels. METHODS: Forty male Sprague-Dawley rats were randomized into 10 groups, each consisting of 10 rats. Groups 1 and 2 consisted of anesthesia and sham-operated control rats, respectively. In the study groups, 10 mm Hg (group 3) and 15 mm Hg (group 4) pneumoperitoneum with CO2 were accomplished. At the end of the procedures, the brains and adrenals were removed quickly, and the hypothalamus and adrenal medulla separated, weighed, and homogenized. TH activity and TP levels were determined. RESULTS: The adrenal medulla TP and TH activity levels were decreased consistently and this decrease was significant in the sham and pneumoperitoneum groups compared with the control group (P<0.05). The adrenal medulla TP and TH activity levels were reduced significantly in group 4, as compared with the other groups (P<0.05). Elevation of hypothalamic TH activity in group 4 was significantly higher than in the other groups (P<0.05). CONCLUSIONS: These results indicate that CO2 pneumoperitoneum applied with 10 and 15 mm Hg pressure gradually decreases the adrenal medulla TH activity; TH is an indispensable enzyme for the biosynthesis of catecholamines. CO2 pneumoperitoneum with 15 mm Hg pressure significantly elevated hypothalamus TH activity.

The effects of enalapril maleate and cold stress exposure on tyrosine hydroxylase activity in some rat tissues.

Enalapril is a highly specific and competitive inhibitor of angiotensin-I converting enzyme (ACE) and thus belongs to the category of ACE inhibitors. The beneficial effects of ACE inhibitors appear to result primarily from the suppression of the plasma renin-angiotensin-aldesterone system. This study was designed to detect the effects of enalapril maleate and cold stress on tyrosine hydroxylase (TH) activity in adrenal medulla, heart and hypothalamus in rat. In cold stress treatment (exposed to 8 degrees C cold for 48 h) TH activity was found to be raised significantly (p < 0.05) in adrenal medulla, hypothalamus and heart tissues. In the adrenal medulla, hypothalamus and heart tissues, TH activity of enalapril maleate treated rats (10 mg kg(-1) body weight) group was not raised significantly (p > 0.05). Following intraperitoneal injection of enalapril maleate (10 mg kg(-1) body weight) the rats were exposed to 8 degrees C cold for 48 h. After cold stress and enalapril maleate treatment no statistically significant change in tyrosine hydroxylase activity was detected in adrenal medulla, hypothalamus or heart (p > 0.05). The results of our studies show that enalapril maleate blocks the effect of cold stress on the regulation of TH activity.

Plasma and urinary adrenomedullin levels in children with acute pyelonephritis.

AIM: Adrenomedullin (AM), a novel peptide recently isolated from pheochromocytoma, eliciting vasorelaxing activity, is the strongest among all known peptides. AM has been detected in the adrenal medulla, cardiac tissue, lung and kidney. Immunohistochemical studies have demonstrated the localization of AM in glomeruli, tubules and collecting cells of the kidney. Clinically, plasma and urinary AM levels are altered in patients with different renal disease. The present study aims to determine plasma and urinary AM levels in children with acute pyelonephritis (APN) and compare the results with a control group. MATERIALS AND METHODS: The study group was comprised of 19 patients with APN aged 11.6 +/- 3.7 months (range, 6-18 months) and the control group consisted of 16 cases aged 11.5 +/- 3.2 months (range, 7-16 months). Acute pyelonephritis was diagnosed by clinical, laboratory and imaging methods. Plasma and urinary AM levels were measured by high performance liquid chromotography (HPLC). RESULTS: The plasma AM levels were lower in APN patients (33.40 +/- 2.27 pmol/mL) than in the control group (43.76 +/- 4.27 pmol/mL) (P < 0.001), whereas the urinary AM levels were higher in APN patients (248.58 +/- 140.63 pmol/mg urinary creatinine) than in the control group (49.42 +/- 45.23 pmol/mg) (P < 0.001). Coefficients of correlation between urinary AM levels and C-reactive protein and white blood cells were statistically significant (r = 0.472, P = 0.041; r = 0.555, P = 0.014, respectively). CONCLUSION: Adrenomedullin, a smooth muscle relaxant peptide that is synthesized in urinary tract tissue might have a role in acute pyelonephritis. However, the importance of AM in the pathogenesis of acute pyelonephritis remains to be determined by further detailed studies.

Influence of misoprostol (PGE1) on amniotic fluid and maternal serum adrenomedullin levels.

OBJECTIVE: The purpose of this study was to determine the levels of adrenomedullin (AdM) in amniotic fluid (AF) and maternal serum of misoprostol (PGE1)-induced pregnant women. MATERIALS AND METHODS: A total of 40 women were included in the study: 20 were in active labor and were delivered vaginally and a further 20 were not in labor and misoprostol induction was performed. Women who were undergoing labor induction received 50 microg of misoprostol, which was placed in the posterior fornix of the vagina every 4 hrs until the onset of labor. In each patient, maternal plasma and AF samples were collected. Samples of AF were collected by transvaginal route at the time of rupture of the membranes. The labor was at the same stage in both the groups during the sample collection. In all pregnant subjects, maternal blood samples were drawn from the cubital vein at the time of AF sampling. Amniotic fluid and serum AdM concentration was measured by using reverse-phase high-performance liquid chromatography. RESULTS: Misoprostol-induced pregnant women showed significantly higher AdM concentrations than control pregnant women in AF (79.48 +/- 6.14 pmol/ml versus 21.28 +/- 0.90 pmol/ml, P = 0.000) and maternal serum (88.20 +/- 4.34 pmol/ml versus 29.78 +/- 4.51 pmol/ml, P = 0.000). There was no significant difference between maternal serum and AF-AdM concentrations in misoprostol and control subjects. CONCLUSION: Increased serum and AF-AdM concentrations may be necessary to initiate cervical ripening in misoprostol-induced pregnant women.

Plasma and urinary adrenomedullin levels in children with renal parenchymal scar and vesicoureteral reflux.

Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and antiproliferative effects in renal mesangial cells, as well as diuretic and natriuretic actions. Its gene expression is stimulated by endotoxins (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels are known to deviate from normal levels in many renal diseases. The purpose of this study is to determine plasma and urinary AM levels in children with renal parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out on 74 children with recurrent urinary tract infections, arranged in groups: 25 patients with RPS with VUR (group I), 16 patients with RPS without VUR (group II), 12 patients with VUR without RPS (group III) and 21 healthy children as the control group. Plasma and urinary AM concentrations were both determined by high performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum creatinine, creatinine clearance and fractional sodium excretion (FE(Na)) were measured. All cases with RPS and VUR had normal blood pressure levels. The plasma AM levels were higher, although not significantly, in the control group (56.2+/-14.0 pM/ml) than in group I (50.6+/-4.2 pM/ml), group II (49.6+/-3.7 pM/ml) and group III (50.6+/-3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in the control group (80.1+/-33.9 pM/mg) than in the three study groups (52+/-7.6 pM/mg, 58.6+/-7.5 pM/mg and 44.2+/-6.4 pM/mg; P =0.003, P =0.002 and P =0.002, respectively). There were no differences among the 4 groups (group I, group II, group III and the control group) in terms of FE(Na) and creatinine clearance ( P >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels in patients with RPS and VUR implies that AM can be a prognostic factor in the long-term follow-up of cases with these diseases.

Adrenomedullin and total nitrite levels in children with acute rheumatic fever.

OBJECTIVE: To investigate the levels of adrenomedullin (AM) and total nitrite, a stable product of nitric oxide (NO), in children with acute rheumatic fever (ARF). DESIGN AND METHODS: Eleven children with ARF were investigated in comparison with 14 healthy controls. Adrenomedullin was detected by HPLC, while total nitrite was quantitated by the Griess reaction. RESULTS: Plasma urinary AM and total nitrite levels were significantly higher in children with ARF, irrespective of whether they were in the acute or convalescent phase of disease. Plasma AM (pmol/mL) levels were 49.19 +/- 3.23 in the acute phase, 44.52 +/- 4.26 in the convalescent phase, 35.49 +/- 3.43 in controls, and urinary AM excretion (pmol/mg creatinine) was 43.45 +/- 18.40 in the acute phase, 32.38 +/- 15.37 in the convalescent phase, and 24.84 +/- 11.38 in controls. Plasma total nitrite levels (mumol/L) were 75.37 +/- 13.13 in the acute phase, 59.81 +/- 12.78 in the convalescent phase, and 41.09 +/- 10.27 in controls. Urinary total nitrite excretion (mumol/mg creatinine) was 3.82 +/- 1.56 in the acute phase, 2.15 +/- 0.58 in the convalescent phase, and 1.33 +/- 0.61 in controls. The differences were statistically significant for all (P < 0.05). CONCLUSION: This study considered that AM and NO may have a role in the immunoinflammatory process of ARF.

Adrenomedullin and leptin levels in diabetic retinopathy and retinal diseases.

PURPOSE: Proliferative and vascular retinal diseases are important cause of irreversible blindness. Consistent features of these diseases are endothelial dysfunction and angiogenesis. Adrenomedullin (ADM) is a multifunctional vasorelaxant peptide. Leptin is a recently discovered metabolic peptide that regulates energy metabolism in human. In the present study, we aimed to investigate the possible roles of adrenomedullin and leptin in the pathophysiology of diabetic and proliferative diseases. METHODS: Ten patients with proliferative diabetic retinopathy (57.1 years, 5 female and 5 male) and 8 patients (51 years, 5 female and 3 male) with other retinal diseases including macular hole and epiretinal membrane were included in this study. All the patients had undergone pars plana vitrectomy for complications of the diseases. Vitreous samples were collected by vitreous tap during the vitrectomy. Adrenomedullin analysis was made by using reverse-phase high-performance liquid chromatography (HPLC). Leptin was measured by enzyme-linked immunosorbent assay (ELISA). Body mass index (BMI) [weight (kg)/height (m2)] was calculated for each group. The Mann-Whitney U test was used for statistics. RESULTS: The age, gender ratio and BMI were not substantially different between the two groups. The mean vitreous adrenomedullin levels (63.9+/-7.1 pmol/l) were significantly higher (p<0.05) in group I than in group II (34.25+/-3.0 pmol/l). Leptin levels in vitreous (4.54+/-1.6 ng/ml) were also significantly higher (p<0.05) in patients with diabetic retinopathy than in those without diabetes (1.83+/-0.5 ng/ml). CONCLUSION: Increased adrenomedullin and leptin levels in vitreous humor might be a possible newly associated factor in the course of vascular and proliferative retinal diseases.

Decreased adrenomedullin and total nitrite levels in breast milk of preeclamptic women.

OBJECTIVE: To observe the adrenomedullin (AM) and total nitrite levels in the milk of preeclamptic and normal pregnant women. DESIGN AND METHODS: Fifteen women with preeclampsia and 15 normal pregnant women were included in the study. Total nitrite was quantitated by Griess reaction, while AM was measured by HPLC. RESULTS: The levels of AM and total nitrite in colostrum and 30th-day breast milk were decreased in preeclamptics. Total nitrite levels (micromol/l) were 56.09 +/- 11.18 vs. 82.20 +/- 12.01, P < 0.05, in colostrum of preeclamptics and controls, respectively. The level of total nitrite was 37.75 +/- 12.10 vs. 53.28 +/- 10.25, P < 0.05, in 30th-day milk of same patients. AM levels (pg/ml) were 11.18 +/- 1.11 vs. 16.59 +/- 1.24, P < 0.0001, in colostrum of preeclamptics and controls, respectively. In 30th-day milk of same patients, AM levels were 8.41 +/- 1.39 vs. 12.18 +/- 1.48, P < 0.005, respectively. CONCLUSION: This report shows for the first time that human milk has decreased levels of AM and total nitrite in preeclampsia.

The effect of adrenomedullin (ADM) on tyrosine hydroxylase (TH) enzyme activity and blood pressure in cold exposed rats.

It is known that, under stress conditions the hypothalamo-pituitary-adrenal (HPA) axis is stimulated and catecholamine production is increased. Adrenomedullin (ADM) is a novel peptide that elicits a long-vasorelaxation, and participates in blood pressure regulation via different mechanisms. In the present study, we investigated the administration of ADM on tyrosine hydroxylase (TH) enzyme activity in cold exposed rats. Four groups of Sprague-Dawley rats were studied for their TH enzyme activity in the adrenal medulla and hypothalamus. In addition to measuring blood pressure in these rats, TH enzyme activity in both the adrenal medulla and hypothalamus were examined in four groups of Sprague-Dawley rats: animals exposed to room temperature and cold stress (8 masculine C, 48 h), and rats injected with ADM (1.0 nmol/kg, i.v.) alone and/or together with cold stress. TH activity was shown to be increased in cold treated groups and decreased in ADM and ADM + cold stress group. Our findings appear to suggest that external ADM application caused an opposite effect on the same system in rats, decreasing the activity of tyrosine hydroxylase (TH) enzyme activity. Furthermore, externally applied ADM was shown to produce its expected hypotensive effect in cold-stressed rats. Our results suggest that a possible explanation for the effects of ADM is that, the uptake of ADM under cold stress may effect TH activity in studied tissues.