Histopathological, ultrastructural, and immunohistochemical examination of changes in the placenta as a result of severe preeclampsia

Purpose: To investigate the role of hypoxia-inducible transcription factor-1 alpha (HIF-1α) and angiogenetic factor endothelin-1 (ET-1) expression in regulating hypoxia and placental development by routine histopathological methods. Methods: Twenty preeclamptic and normal placentas were used. Placenta tissue pieces were examined histopathologically after routine paraffin follow-ups. HIF-1α and ET-1 proteins were examined immunohistochemically, and placental tissues were examined ultrastructurally. Results: Increase in syncytial proliferation, endothelial damage in vessels, and increase in collagen were observed in preeclamptic placentas. As a result of preeclampsia, an increase was observed in HIF-1α and ET-1 protein levels in the placenta. Dilatation of endoplasmic reticulum and loss of cristae in mitochondria were observed in trophoblast cells in preeclamptic placental sections. Conclusion: High regulation of oxygen resulting from preeclampsia has been shown to be a critical determinant of placentagenesis and plays an important role in placental differentiation, changes in maternal and fetal blood circulation, trophoblastic invasion, and syncytial node increase. It has been thought that preeclampsia affects secretion by disrupting the endoplasmic reticulum structure and induces mitochondrial damage, and that ET-1 may potentially help in the induction of stress pathways as a result of hypoxia in preeclampsia.

Refractory Digital Ulcers Treated by Botulinum Toxin and Endothelin Receptor-1 Antagonist in Anti-MDA5-Antibody-Positive Dermatomyositis

No abstract available.

Effect of Ambrisentan Therapy on the Expression of Endothelin Receptor, Endothelial Nitric Oxide Synthase and NADPH Oxidase 4 in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model

BACKGROUND AND OBJECTIVES: Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model. METHODS: Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCT injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis. RESULTS: Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4. CONCLUSIONS: Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment.

Moving Beyond the Endothelium is Still Challenging-Complex Interplay between Endothelin and Reactive Oxygen Species in Pulmonary Arterial Hypertension

No abstract available.

Change of voltage-gated potassium channel 1.7 expressions in monocrotaline-induced pulmonary arterial hypertension rat model / 소아과

PURPOSE: Abnormal potassium channels expression affects vessel function, including vascular tone and proliferation rate. Diverse potassium channels, including voltage-gated potassium (Kv) channels, are involved in pathological changes of pulmonary arterial hypertension (PAH). Since the role of the Kv1.7 channel in PAH has not been previously studied, we investigated whether Kv1.7 channel expression changes in the lung tissue of a monocrotaline (MCT)-induced PAH rat model and whether this change is influenced by the endothelin (ET)-1 and reactive oxygen species (ROS) pathways. METHODS: Rats were separated into 2 groups: the control (C) group and the MCT (M) group (60 mg/kg MCT). A hemodynamic study was performed by catheterization into the external jugular vein to estimate the right ventricular pressure (RVP), and pathological changes in the lung tissue were investigated. Changes in protein and mRNA levels were confirmed by western blot and polymerase chain reaction analysis, respectively. RESULTS: MCT caused increased RVP, medial wall thickening of the pulmonary arterioles, and increased expression level of ET-1, ET receptor A, and NADPH oxidase (NOX) 4 proteins. Decreased Kv1.7 channel expression was detected in the lung tissue. Inward-rectifier channel 6.1 expression in the lung tissue also increased. We confirmed that ET-1 increased NOX4 level and decreased glutathione peroxidase-1 level in pulmonary artery smooth muscle cells (PASMCs). ET-1 increased ROS level in PASMCs. CONCLUSION: Decreased Kv1.7 channel expression might be caused by the ET-1 and ROS pathways and contributes to MCT-induced PAH.

Bone-targeted therapies to reduce skeletal morbidity in prostate cancer / 亚洲男科学杂志(英文版)

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

rBMSCs/ITGA5B1 Promotes Human Vascular Smooth Muscle Cell Differentiation via Enhancing Nitric Oxide Production

BACKGROUND AND OBJECTIVES: Previous studies have shown that integrins alpha5beta1 (ITGA5B1) gene-modified rat bone marrow mesenchymal stem cells (rBMSCs) could prevent cell anoikis and increase the nitric oxide (NO) production. Here we examined the capability of rBMSCs/ITGA5B1 on the phenotype modulation of Human Pulmonary Artery Smooth Muscle Cell (HPASMC) in vitro. METHODS AND RESULTS: The synthetic (dedifferentiated) phenotype of HPASMC was induced by monocrotaline (MCT, 1μM) for 24 h and then co-cultured with rBMSCs/ITGA5B1 in a transwell culture system. The activation of NO/cGMP (nitric oxide/Guanosine-3′, 5′-cyclic monophosphate) signaling was investigated in HPASMC. The changes of pro-inflammatory factors, oxidative stress, vasodilator, vasoconstrictor, contractile and synthetic genes, and the morphological changes of HPASMC were investigated. The results of this study showed that the NO/cGMP signal, endothelial nitric oxide synthase (eNOS) expression, the expression of the vasoprotective genes heme oxygenase-1 (HMOX1) and prostaglandin-endoperoxide synthase 2 (PTGS2) were increased, but the expression of transforming growth factor-β1 (TGF-β1), CCAAT/enhancer-binding proteins delta (Cebpd), Krüppel-like factor 4 (KLF4), and activating transcription factor 4 (ATF4) were reduced in MCT treated HPASMC co-cultured with rBMSCs/ITGA5B1. The synthetic smooth muscle cells (SMCs) phenotype markers thrombospondin-1, epiregulin and the vasoconstrictor endothelin (ET)-1, thromboxane A2 receptor (TbxA2R) were down-regulated, whereas the contractile SMCs phenotype marker transgelin expression was up-regulated by rBMSCs/ITGA5B1. Furthermore, rBMSCs/ITGA5B1 promoted the morphological restoration from synthetic (dedifferentiation) to contractile (differentiation) phenotype in MCT treated HPASMC. CONCLUSIONS: rBMSCs/ITGA5B1 could inhibit inflammation and oxidative stress related genes to promote the HPASMC cell differentiation by activation NO/cGMP signal.

Association of endotheline receptor gene rs1878406 polymorphism with severe multi-vessel coronary disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of single nucleotide polymorphisms (SNPs) of endotheline receptor gene with the severity of coronary heart disease (CHD).</p><p><b>METHODS</b>A total of 553 CHD patients, including 324 patients with mult-vessel disease based on result of selected coronary angiography, and 553 age- and sex-frequency matched controls were selected. Clinical data were collected. Genotypes of rs501120, rs899997, rs1878406 and rs7173743 were determined with TaqMan-MGB probes.</p><p><b>RESULTS</b>The distribution of genotypes of the 4 SNPs showed no significant difference between the two groups. However, the frequency of A allele of rs501120 and T allele of rs1878406 were significantly higher in the CHD group compared with the control group (P< 0.05). For rs7173743 and rs899997, no significant difference was detected between the two groups. After adjusting for conventional risk factors by logistic regression analysis, the results suggested that the distribution of rs1878406 TT+TC genotype in severe multi-vessel disease group is significantly higher than that in the control group (OR=1.43, 95% CI: 1.05-2.07, P=0.033).</p><p><b>CONCLUSION</b>The above results suggested that the rs1878406 polymorphism of endotheline receptor gene may serve as a genetic marker for severe multi-vessel disease in CHD among ethnic Han Chinese.</p>

The first Korean case of Waardenburg-Shah syndrome with novel endothelin receptor type B mutations

Waardenburg syndrome (WS) is a rare genetic disorder, including clinical features of pigmentary abnormalities of irides, skin, hair and sensorineural hearing loss and facial dysmorphism. Among the four types, WS type IV (Waardenburg-Shah syndrome) additionally represents Hirschsprung's disease. Mutations in the SOX10, END3, or EDNRB genes are known to cause WS type IV. Here, we report a 6 year-old girl who was diagnosed as WS type IV by typical clinical manifestations, including skin hypopigmentation, heterochromia of both irides, unilateral sensorineural hearing loss, mild developmental delay and Hirschsprung's disease. The diagnosis was confirmed by molecular genetic analysis of EDNRB. Two novel EDNRB mutations were identified, and each mutation was segregated from each of her parents. During the follow-up period, the patient underwent a surgery for spleen torsion and was medically managed due to recurrent enterocolitis. Also, she suffered from impaired immunity including Hirschsprung's associated enterocolitis.

Neuroendocrine Dysregulation in Irritable Bowel Syndrome Patients: A Pilot Study

BACKGROUND/AIMS: Irritable bowel syndrome (IBS) is a multifactorial disorder, involving dysregulation of brain-gut axis. Our aim was to evaluate the neuroendocrine activity in IBS. METHODS: Thirty IBS and 30 healthy volunteers were enrolled. Psychological symptoms were evaluated by questionnaires. Urinary 5-hydroxyindoleacetic acid, plasma serotonin (5-hydroxytryptamine, 5-HT), endothelin, and neuropeptide Y (NPY), and plasma and urinary cortisol levels were evaluated. Fourteen IBS subjects underwent microneurography to obtain multiunit recordings of efferent postganglionic muscle sympathetic nerve activity (MSNA). RESULTS: Prevalent psychological symptoms in IBS were maladjustment (60%), trait (40%) and state (17%) anxiety, obsessive compulsive-disorders (23%), and depressive symptoms (23%). IBS showed increased NPY (31.9 [43.7] vs 14.8 [18.1] pmol/L, P = 0.006), 5-HT (214.9 [182.6] vs 141.0 [45.5] pg/mL, P = 0.010), and endothelin [1.1 [1.4] vs 2.1 [8.1] pg/mL, P = 0.054], compared to healthy volunteers. Moreover, plasma NPY, endothelin, cortisol and 5-HT, and urinary 5-hydroxyindoleacetic acid were associated with some psychological disorders (P ≤ 0.05). Despite a similar resting MSNA, after cold pressor test, IBS showed a blunted increase in MSNA burst frequency (+4.1 vs +7.8 bursts/min, P = 0.048; +30.1% vs +78.1%, P = 0.023). Baseline MSNA tended to be associated with urinary cortisol (ρ = 0.557, P = 0.059). Moreover, changes in heart rate after mental stress were associated with urinary cortisol (ρ = 0.682, P = 0.021) and changes in MSNA after mental stress were associated with plasma cortisol (ρ = 0.671, P = 0.024).” CONCLUSION: Higher concentrations of endothelin, NPY, and 5-HT were found to be associated with some psychological disorders in IBS patients together with an altered cardiovascular autonomic reactivity to acute stressors compared to healthy volunteers.

Effects of Danhong Injection (丹红注射液) and its main components on anticoagulation and fibrinolysis in cultured vein endothelial cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the effects of Danhong Injection (丹红注射液) and its main components, including daiclzein and hydroxysafflor yellow A (HSYA), on the anticoagulation, fibrinolysis, anti-apoptosis in hypoxia model of vein endothelial cells (VECs).</p><p><b>METHODS</b>VECs were prepared and were put in a hypoxia environment, which consisted of mixed gas of 95% N and 5% CO mixed gas, when reached confluent culture. Five groups used different treatments, including normal control group, hypoxia group, daiclzein group, HSYA group and Danhong Injection group. The VECs were identified by fluorescence double labeling methods. The morphology was observed by a phase contrast microscopy. The effects of Danhong Injection, daiclzein and HSYA on 6 keto prostaglandin F1α (6-keto-PGF1α) level was measured by the method of radioimmunoassay (RIA). Superoxide dismutase (SOD) activity was tested by water soluble tetrazolium salt. The content of malondialdehyde (MDA) was measured by thiobarbituric acid. The activities of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were measured by the method of chromogenic substrate. The contents of endothelin (ET) and nitric oxide (NO) were detected by non-equilibrium RIA and enzymelinked immunosorbent assay. Cells apoptosis rate was determined by flow cytometry.</p><p><b>RESULTS</b>Compared with the normal control group, the floating cells number, PAI activity, ET and MDA contents, and cells apoptosis rate in the culture solution of hypoxia group were all significantly increased, whereas the 6-keto-PGF1α and NO contents, and t-PA and SOD activities were decreased significantly (P<0.01). Compared with the hypoxia group, Danhong Injection markedly increased the 6-keto-PGF1α content and SOD activity, regulated PAI and t-PA activities, ET and NO contents, and decreased MDA content and cells apoptosis rate (P<0.05 or P<0.01).</p><p><b>CONCLUSIONS</b>Danhong Injection and its main components played an important role in protecting primary VECs from hypoxic damage by regulating the secretion and vasomotor function of VECs. The function of Danhong Injection was most remarkable.</p>

The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure / 소아과

PURPOSE: Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. METHODS: The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. RESULTS: The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. CONCLUSION: Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function.

The clinical significance and changes of serum tumor necrosis factor and plasma endothelium in patients with OSAHS associated Type 2 diabetes mellites / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the significance of tumor necrosis factor-alpha (TNF-α) and plasma endothelium (ET) in pathophysiologic process of patients with obstructive sleep apnea hypopnea syndrome(OSAHS) with type 2 diabetes mellitus (T2DM).@*METHOD@#All observed subjects were divided into 4 groups. A number of 80 patients with OSAHS, 65 cases of OSAHS with T2DM patients, 20 patients with T2DM, and 32 cases of healthy control group were observed in this study. The serum levels of TNF-α and ET were detected by double antibody sandwich ELISA, the content of TNF-α and ET were compared between OSAHS group and OSAHS + T2DM group. It were also compared before and after treatment of CPAP or surgery.@*RESULT@#TNF-α level is higher in OSAHS+T2DM group than that in the OSAHS group, T2DM group and the control group (P 0.05).@*CONCLUSION@#TNF-α may be involved in the development of OSAHS and T2DM, while ET may have little effect on the occurrence and development of OSAHS and T2DM.

Childhood Hearing Health: Educating for Prevention of Hearing Loss

Introduction The presence of noise in our society has attracted the attention of health professionals, including speech-language pathologists, who have been charged along with educators with developing hearing conservation programs in schools. Objective To describe the results of three strategies for awareness and hearing preservation in first to fourth grades in public elementary schools. Methods The level of environmental noise in classrooms was assessed, and 638 elementary school students from first to fourth grades, 5 to 10 years of age, were audiologically evaluated. After the evaluations, educational activities were presented to children and educators. Results The noise level in the classroom ranged from 71.8 to 94.8 A-weighted decibels. The environment of the classroom was found to promote sound reverberation, which hinders communication. Thirty-two students (5.1%) presented hearing alterations. Conclusion The application of strategies for a hearing conservation program at the school showed that noise is present in the room, and hearing loss, sometimes silent, affects schoolchildren. Students and teachers were aware that hearing problems can be prevented. Avoiding exposure to noise and improving the acoustics in classrooms are essential. .

Clinical significance of dynamic changes in serum inflammatory cell factors after acute paraquat poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the clinical significance of dynamic changes in the serum inflammatory cell factors consisting of β-endorphin (β-EP) , endothelins (ET) , tumor necrosis factor (TNF) , and nitric oxide (NO) after acute paraquat poisoning (APP).</p><p><b>METHODS</b>The 26 patients with APP (as observation group) were treated and the serum levels of plasma β-EP, ET, TNF, and NO were measured simultaneously. The 20 healthy volunteers from relatives of the patients (as control group) were also included in the study and their serum levels of β-EP, ET, TNF, and NO were measured.</p><p><b>RESULTS</b>In the 26 patients with APP, 10 were cured and 16 died. The serum levels of β-EP, ET, NO, and TNF in the 10 cured patients increased significantly immediately after admission, reached the peak values on day 2, and then decreased gradually and returned to the normal ranges after day 9. The serum levels of β-EP, ET, NO, and TNF in the 16 dead patients increased significantly on admission and kept rising in the course of treatment. The dead patients had significantly increased serum levels of β-EP, ET, NO, and TNF compared with the cured patients (all P<0.01).</p><p><b>CONCLUSION</b>Compared with those in cured patients with APP, the serum levels of β-EP, ET, NO, and TNF in dead patients with APP are significantly higher, keep rising, and maintain at high levels, indicating a severe condition.</p>

Effect of Enhanced External Counterpulsation and Cardiac Rehabilitation on Quality of Life, Plasma Nitric Oxide, Endothelin 1 and High Sensitive CRP in Patients With Coronary Artery Disease: A Pilot Study

OBJECTIVE: To investigate the effect of enhanced external counterpulsation (EECP) on plasma nitric oxide (NO), Endothelin 1 (ET1), high sensitive C-reactive protein (HSCRP) and quality of life (QoL) in patients with coronary artery disease (CAD). METHODS: We conducted a pilot randomized clinical trial in order to evaluate plasma NO, ET1, HSCRP and QoL before and after twenty sessions of EECP (group A) and cardiac rehabilitation (CR, group B) in 42 patients with CAD (21 in each group). RESULTS: Forty-two patients (33 male and 9 female) were included in the study. The mean age was 58.2+/-10 years. The mean HSCRP was 1.52+/-0.7 in the EECP group and it was reduced to 1.27+/-0.4 after intervention. The reduction in HSCRP was not statistically significant in EECP and CR groups with p=0.33 and p=0.27, respectively. There was not significant improvement of NO, ET1, and QoL in the EECP and CR groups shortly after therapy (p>0.05). CONCLUSION: Although the short-term EECP treatment in CAD patients improved HSCRP, NO, ET1, and QoL compared with the baseline those improvements are not statistically significant. Further studies are necessary with large study groups and more sessions.

Familial mitral valve prolapse in a Maltese dog family / 동물의과학연구지

Mitral valvular prolapse (MVP) in dogs is characterized by myxomatous valvular degeneration, which is caused by abnormal valvular thickening and incomplete coaptation of the mitral valve leading to mitral regurgitation. Mitral regurgitation causes left atrial and left ventricular enlargement. Pathogenesis of the disease is unknown, although some studies have suggested the involvement of endothelin and systemic connective tissue diseases. Mitral valvular prolapse in dogs commonly occurs in aged small dog breeds, including Malteses and Shih Zhus. This case study investigated the clinical features of an affected Maltese family and performed pedigree analysis. To the best of the authors' knowledge, this is the first report of putative familial mitral valve prolapse and regurgitation in Maltese dogs. All family members in this study showed degenerative valvular changes and echocardiographic features of mitral valvular prolapse. Although disease progression differed, all dogs progressed to advanced heart failure stage within 2-3 years after diagnosis. Therefore, this is the first study to identify putative familial mitral valve prolapse in Maltese dogs. This finding suggests strong genetic etiology involved in the development of degenerative mitral valve disease in Maltese dogs. Furthermore, this finding could be a valuable resource for the identification of gene mutations in dogs with familial mitral valvular prolapse.

Vascular dysfunction as a target for adjuvant therapy in cerebral malaria

Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum malaria that continues to be a major global health problem. Brain vascular dysfunction is a main factor underlying the pathogenesis of CM and can be a target for the development of adjuvant therapies for the disease. Vascular occlusion by parasitised red blood cells and vasoconstriction/vascular dysfunction results in impaired cerebral blood flow, ischaemia, hypoxia, acidosis and death. In this review, we discuss the mechanisms of vascular dysfunction in CM and the roles of low nitric oxide bioavailability, high levels of endothelin-1 and dysfunction of the angiopoietin-Tie2 axis. We also discuss the usefulness and relevance of the murine experimental model of CM by Plasmodium berghei ANKA to identify mechanisms of disease and to screen potential therapeutic interventions.

Ameliorative Effect of a Selective Endothelin ETA Receptor Antagonist in Rat Model of L-Methionine-induced Vascular Dementia

The present study was designed to investigate the efficacy of selective ET(A) receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from 5th to 8th week of L-methionine treatment). On 52nd day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective ET(A) receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.

Effect of peroxisome proliferator-activated receptor gamma agonist on heart of rabbits with acute myocardial ischemia/reperfusion injury

OBJECTIVE@#To explore protective effect of rosiglitazone on myocardial ischemia reperfusion injury.@*METHODS@#A total of 48 male SD rats were randomly divided into control group (A), I/R group(B), high dose of rosiglitazone (C), low dose of rosiglitazone (D). Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), nitric oxide (NO) and endothelin (ET) were measured 1 h later after I/R. 24 h after I/R hearts were harvested to observe pathological and ultrastructural changes. Immunohistochemistry and western blotting was used to test CD40 expression in myocardial tissue. Area of myocardial infarction were tested, arrhythmia rate during I/R was recorded.@*RESULTS@#Plasm concentration of creatine kinase (CK), CK-MB, hsCRP, NO, MDA and ET were decreased in group C, D compared with group B. Plasm concentration of T-SOD and GSH-Px was increased significantly in group C, D compared with group B. Compared with group B, pathological and ultrastructural changes in group C, D were slightly. Myocardial infarction area and arrhythmia rate were lower in group C, D compare with group B.@*CONCLUSIONS@#Rosiglitazone can protect myocardium from I/R injury by enhancing T-SOD and GSH-Px concentration, inhibit inflammatory reaction, improve endothelial function, reduce oxidative stress and calcium overload.