Protective effect of adrenomedullin on hyperoxia-induced lung injury / 中国当代儿科杂志

OBJECTIVES@#To study the role of adrenomedullin (ADM) in hyperoxia-induced lung injury by examining the effect of ADM on the expression of calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein 2 (RAMP2), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB) in human pulmonary microvascular endothelial cells (HPMECs) under different experimental conditions.@*METHODS@#HPMECs were randomly divided into an air group and a hyperoxia group (@*RESULTS@#Compared with the air group, the hyperoxia group had significant increases in the mRNA and protein expression levels of ADM, CRLR, RAMP2, ERK1/2, and PKB (@*CONCLUSIONS@#ERK1/2 and PKB may be the downstream targets of the ADM signaling pathway. ADM mediates the ERK/PKB signaling pathway by regulating CRLR/RAMP2 and participates in the protection of hyperoxia-induced lung injury.

Study of surface activity of piroxicam at the interface of palm oil esters and various aqueous phases

The surface activity of some non-steroidal anti-inflammatory agents like ibuprofen was investigated extensively. This fact has attracted the researchers to extend this behavior to other agents like piroxicam. Piroxicam molecules are expected to orient at the interface of oil and aqueous phase. The aim of this study was, firstly, to assess the surface and interfacial tension behaviour of newly synthesised palm oil esters and various pH phosphate buffers. Furthermore, the surface and interfacial tension activity of piroxicam was studied. All the measurements of surface and interfacial tension were made using the tensiometer. The study revealed that piroxicam has no effect on surface tension values of all pH phosphate buffers and palm oil esters. Similarly, various concentrations of piroxicam did not affect the interfacial tensions between the oil phase and the buffer phases. Accordingly, the interfacial tension values of all mixtures of oil and phosphate buffers were considerably high which indicates the immiscibility. It could be concluded that piroxicam has no surface activity. Additionally, there is no surface pressure activity of piroxicam at the interface of palm oil esters and phosphate buffers in the presence of Tweens and Spans

Effect and mechanism of intermedin in acute rat cardiac ischemic injury / 法医学杂志

OBJECTIVE@#To investigate the effect and potential mechanism of intermedin (IMD) in acute cardiac ischemic injury and to provide a new approach for exploring mechanism of sudden cardiac death.@*METHODS@#Seventy-two healthy male rats were randomly divided into 3 groups: control, ischemic and the IMD-treated group. The activity of lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) in heart blood were tested by enzyme chemistry method. The mRNA changes of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs) in cardiac were measured by real-time PCR analysis. Myocardial cyclic adenosine monophosphate (cAMP) content was determined by enzyme linked immunosorbent assay (ELISA). Apoptosis related factors Bcl-2 and Bax were detected by immunohistochemistry.@*RESULTS@#Comparing with the control group, LDH and MDA activity of ischemic group in heart blood increased and SOD activity decreased. The concentration of cAMP increased in ventricular muscle, Bcl-2 and Bax proteins expression ratio level decreased. The intravenation of IMD decreased the level of increased activity of LDH and MDA, and lessened the level of decreased activity of SOD. The mRNA expression of CRLR and RAMPs obviously increased in ventricular muscle.@*CONCLUSION@#The protective effect of IMD against myocardial ischemic injury could be caused by decreasing the oxidative stress of ischemia and inhibiting the myocardial apoptosis.

Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle of rats with chronic hypoxic pulmonary hypertension / 生理学报

The purpose of the present study was to explore the expression changes of intermedin/adrenomedullin 2 (IMD/ADM2), a novel small molecular bioactive peptide, and its receptors, calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMP1, RAMP2, RAMP3) in the right ventricle of rats with chronic hypoxia-induced pulmonary hypertension. Twenty male Sprague-Dawley rats were randomly divided into 4-week hypoxia group and normal control group (each n=10). The rats in hypoxia group were placed in an isobaric hypoxic chamber, in which O(2) content was maintained at 9%-11% by delivering N(2), and CO(2) content was maintained at <3% for 4 weeks (8 h/d, 6 d/week). The rats in the control group were housed in room air. The protein levels of IMD/ADM2 and adrenomedullin (ADM) in blood plasma and right ventricular tissue were measured by radioimmunoassay. The mRNA expressions of IMD/ADM2, ADM and their receptors CRLR, RAMP1, RAMP2, RAMP3 in right ventricular tissue were determined by reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the ratio of right ventricle weight to left ventricle plus septum weight [RV/(LV+S)] and mean pulmonary arterial pressure (mPAP) were higher in hypoxia group than those in the control group (all P<0.01), suggesting that the rat model of pulmonary hypertension was successfully established. However, the mean carotid arterial pressure (mCAP) between the two groups had no significant difference. Compared with that in the control group, ADM contents in plasma and right ventricular tissue in hypoxia group increased by 1.26 and 1.68 folds (all P<0.01), respectively. Likewise, IMD/ADM2 contents in blood plasma and right ventricular tissue in hypoxia group increased by 0.90 and 1.19 folds (P<0.01), respectively, compared with that in the control group. The data of RT-PCR showed that mRNA levels of ADM, IMD/ADM2 and RAMP2 in hypoxia group increased by 155.1% (P<0.01), 80.9% (P<0.01) and 52.9% (P<0.05), respectively, compared with those in the control group. There were no significant differences in mRNA expressions of CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the results show that the level of IMD/ADM2 increases in the rats with chronic hypoxia-induced pulmonary hypertension.

Expression of adrenomedullin and its receptor mRNA in the tissues of normal adrenal medulla and pheochromocytoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of human adrenomedullin (ADM) and its receptor-receptor activity modifying protein 2/calcitonin receptor-like receptor (RAMP2/CRLR) mRNA in the tissues of normal adrenal medulla and pheochromocytoma.</p><p><b>METHODS</b>Total RNA was extracted from normal adrenal medulla and pheochromocytomas. The expression of ADM and RAMP2/CRLR mRNA were studied by reverse transcription-polymerase chain reaction. The ratios of ADM/GAPDH, RAMP2/ GAPDH, CRLR/GAPDH were used to evaluate the expression levels of ADM, RAMP2 and CRLR mRNA.</p><p><b>RESULTS</b>Expressions of ADM and its receptor- RAMP2/CRLR mRNA were detected in normal adrenal medulla and pheochromocytoma tissues. ADM/GAPDH were 0.48+/-0.09 and 0.75+/-0.24, RAMP2/ GAPDH 0.79+/-0.12 and 1.29+/-0.30, CRLR/GAPDH 0.40+/-0.08 and 0.87+/-0.22 in normal adrenal medulla and pheochromocytomas, respectively (P < 0.05).</p><p><b>CONCLUSION</b>ADM exerts a possible autocrine or paracrine effect in the adrenal. ADM may be involved in the pathogenesis of pheochromocytoma.</p>

Increased atria expression of receptor activity-modifying proteins in heart failure patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a calcitonin gene related peptide (CGRP) receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an adrenomedullin(ADM) receptor. As CGRP and ADM may play a beneficial role in heart failure, this study aimed at the question whether RAMPs mRNAs are changed in heart failure.</p><p><b>METHODS</b>Semi-quantitative reverse transcription-PCR (RT-PCR) was used to detect and quantify the mRNAs of RAMP1 and RAMP3 in the atria of heart failing patients.</p><p><b>RESULTS</b>It was found that the expressions of RAMP1, RAMP2 and RAMP3 mRNAs increased with the worsening of heart function, but the expressions of RAMP1 and RAMP2 mRNA decreased at level IV of heart failure.</p><p><b>CONCLUSION</b>The above results demonstrated in the atria of heart failure patients an up-regulation of CGRP receptor by an increase of RAMP1 in association with CRLR and an up-regulation of ADM receptor by an increase of RAMP2 expression in association with CRLR, thus suggesting that CGRP and ADM receptors be playing a functional role in compensating the chronic heart failure in human.</p>