Reversal of subcellular remodelling by losartan in heart failure due to myocardial infarction

This study tested the reversal of subcellular remodelling in heart failure due to myocardial infarction (MI) upon treatment with losartan, an angiotensin II receptor antagonist. Twelve weeks after inducing MI, rats were treated with or without losartan (20 mg/kg; daily) for 8 weeks and assessed for cardiac function, cardiac remodelling, subcellular alterations and plasma catecholamines. Cardiac hypertrophy and lung congestion in 20 weeks MI‐induced heart failure were associated with increases in plasma catecholamine levels. Haemodynamic examination revealed depressed cardiac function, whereas echocardiographic analysis showed impaired cardiac performance and marked increases in left ventricle wall thickness and chamber dilatation at 20 weeks of inducing MI. These changes in cardiac function, cardiac remodelling and plasma dopamine levels in heart failure were partially or fully reversed by losartan. Sarcoplasmic reticular (SR) Ca²⁺‐pump activity and protein expression, protein and gene expression for phospholamban, as well as myofibrillar (MF) Ca²⁺‐stimulated ATPase activity and α‐myosin heavy chain mRNA levels were depressed, whereas β‐myosin heavy chain expression was increased in failing hearts; these alterations were partially reversed by losartan. Although SR Ca²⁺‐release activity and mRNA levels for SR Ca²⁺‐pump were decreased in failing heart, these changes were not reversed upon losartan treatment; no changes in mRNA levels for SR Ca²⁺‐release channels were observed in untreated or treated heart failure. These results suggest that the partial improvement of cardiac performance in heart failure due to MI by losartan treatment is associated with partial reversal of cardiac remodelling as well as partial recovery of SR and MF functions.     

冠心病患者的血浆大内皮素与N末端脑钠肽水平及其与心功能的关系

目的:探讨冠心病(CHD)患者血浆大内皮素(Bigendothelin-1,Big ET-1)与N末端脑钠肽(NT-pro BNP)的水平及其与心功能的关系。方法:选择本院2014年1月-2014年5月收治的60例CHD患者为观察组,及同期接受体检的60例健康志愿者作为对照组,测定并比较两组的血浆大内皮素与N末端脑钠肽水平以及不同心功能分级CHD患者的血浆大内皮素与N末端脑钠肽水平的差异,分析血浆大内皮素与N末端脑钠肽水平与CHD患者心功能的关系。结果:观察组患者血浆Big ET-1和NT-pro BNP的水平均显著高于对照组,差异具有统计学意义(P0.05)。随着CHD患者的心功能分级的增加,其血浆Big ET-1和NT-pro BNP的水平逐渐升高,且各组之间比较差异均具有统计学意义(P0.05)。血浆Big ET-1、NT-pro BNP水平与CHD患者的心功能之间存在明显的正相关性(P0.05)。结论:CHD患者的血浆Big ET-1与NT-pro BNP水平均异常升高,且与患者的心功能呈正相关,监测其水平对判断CHD的病情及心功能可能具有重要的临床参考价值。     

Serum A-FABP is increased and closely associated with elevated NT-proBNP levels in type 2 diabetic patients treated with rosiglitazone

Background

Adipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment.

Methodology/Principal Findings

A total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (β = 0.320, P = 0.007).

Conclusions/Significance

Rosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue.     

炙甘草汤加五参颗粒联合西药治疗冠心病的临床疗效及其对患者血清hs-CRP、NT-proBNP水平和内皮功能的影响

目的:探究炙甘草汤加五参颗粒联合西药治疗冠心病的临床疗效及其对患者血清超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、N末端B型脑钠尿肽前体(NT-Pro-brain natriuretic peptide,NT-proBNP)水平和内皮功能的影响。方法:选取2015年12月至2017年10月在我院接受治疗的冠心病患者80例,随机分为观察组和对照组,每组各40例。对照组接受西药治疗,观察组在西药治疗的基础上联合炙甘草汤加五参颗粒治疗。比较两组临床疗效及治疗前后hs-CRP、NT-proBNP、一氧化氮(Nitric oxide,NO)和内皮素(Endothelin-1,ET-1)水平的变化。结果:观察组和对照组治疗后的总有效率分别为90%和72.5%,观察组明显优于对照组(P0.05)。治疗前,两组血清hs-CRP、NT-pro BNP、NO、ET-1水平比较差异无统计学意义(P0.05)。与同组内治疗前比较,两组治疗后血清NT-pro BNP、hs-CRP、ET-1水平均明显下降,血清NO水平均明显升高,且观察组血清NT-proBNP、hs-CRP、ET-1水平均明显低于对照组(P0.05),血清NO水平显著高于对照组(P0.05)。结论:在西药治疗的基础上加用炙甘草汤加五参颗粒治疗冠心病临床疗效明显优于单用西药治疗,可能与其显著降低炎症和改善内皮功能有关。     

Experimental canine histoplasmosis and blastomycosis

Normal adult beagle dogs were experimentally infected withHistoplasma capsulatum orBlastomyces dermatitidis. Clinical signs of histoplasmosis and blastomycosis were similar to those seen in natural infections in dogs, although diarrhea was not seen in dogs with experimental histoplasmosis. Significant radiographic changes were seen in the lungs of all dogs inoculated with one of the organisms but not in the control dogs.Amphotericin B treatment of the dogs infected with mycelia ofBlastomyces dermatitidis resulted in clinical improvement and prevented death, but did not cure all of the dogs. Four of five dogs randomly selected for placebo treatment died within 34 days of inoculation, whereas all five dogs in the amphotericin B treated group were alive 14 weeks after inoculation.Since no deaths occurred in dogs inoculated with the mycelia ofHistoplasma capsulatum, weight loss was used as a measure of the degree of illness. No difference could be demonstrated between weight losses of three dogs treated with amphotericin B and of three dogs treated with a placebo. Four other dogs inoculated withH. capsulatum did not have a 20% weight loss, a criterion for treatment. The 10 control dogs maintained their preinoculation weight.From the Ecological Investigations Program, Center for Disease Control, Health Services and Mental Health Administration, Public Health Service, United States Department of Health, Education, and Welfare, Kansas City, Kansas.     

Application of a Fab fragment of monoclonal antibody specific to <Emphasis Type="Italic">N</Emphasis>-terminal pro-brain natriuretic peptide for the detection based on regeneration-free electrochemical immunosensor

N-Terminal pro-brain natriuretic peptide (NT-proBNP) is an important marker for heart failure that reflects ventricular volume expansion, ventricular overload and the degree of cardiac injury. To establish a sensitive and simple detection method for it in serum, a regeneration-free immunosensor with novel Fab fragment monoclonal antibodies was prepared. The sensor detected NT-proBNP from 0.04 to 2.5 ng/ml with a limit of 0.03 ng/ml. The immunosensor is therefore a simple, cost-effective method to detect NT-proBNP and the proposed immunoassay system would enable other proteins to be detected and open new opportunities for protein diagnostics.     

The ferret, Mustela putorius furo, as a new species in toxicology.

Comprehensive studies on the haematology, urine chemistry, serum chemistry and gross pathology have been carried out and reported. Seasonal weight changes were confirmed and were initiated, together with sexual activity, when ferrets were brought in to a constant temperature (18-19 degrees C) and 14-hour daylight cycle during the winter months. Levels of haemoglobin, erythrocytes and haematocrit were higher than in most common laboratory species. Similarly, serum electrolytes and glucose levels were higher than in Wistar rats or beagle dogs. Ovaries, uteri and testes displayed a seasonal maturation and atrophy. All other parameters were similar to common laboratory species.     

先天性心脏病患儿介入封堵术治疗前后CRP、NT-proBNP、心率变异性的变化及与术后心功能的关系研究

摘要 目的：探讨先天性心脏病（CHD）患儿介入封堵术治疗前后C-反应蛋白（CRP）、N末端B型利钠肽原（NT-proBNP）、心率变异性（HRV）的变化及与术后心功能的关系。方法：选择2020年10月至2021年6月在本院行介入封堵术治疗的95例CHD患儿为研究对象,采用化学发光法检测血清CRP水平,采用电化学发光免疫技术检测血清NT-proBNP水平,采用24 h动态心电图及12导联同步心电图分析HRV指标,观察手术前后患儿的血清CRP、NT-proBNP水平及HRV指标变化,比较术后不同NYHA心功能分级患儿的血清CRP、NT-proBNP水平和HRV指标,分析患儿术前血清CRP水平、血清NT-proBNP水平、HRV指标与术后NYHA心功能分级的相关性。结果：介入封堵术后患儿血清CRP、NT-proBNP、LF/HF水平逐渐降低,术后3 d、术后1个月时均低于术前,术后1个月时均低于术后3 d时（P<0.025）;而TP、HF、LF、R-R、PNN50%、ASDNN、SDANN、SDNN、rMSSD水平逐渐升高,术后3 d、术后1个月时均高于术前,术后1个月时均高于术后3 d 时（P<0.025）。患儿术后3 d的血清CRP、NT-proBNP水平及LF/HF水平随着NYHA心功能分级的升高而升高,TP、HF、LF、R-R、PNN50%、ASDNN、SDANN、SDNN、rMSSD水平随着NYHA心功能分级的升高而降低（多有P＜0.05）。患儿术后3 d的NYHA心功能分级与治疗前血清CRP、NT-proBNP及LF/HF水平呈负相关,与TP、HF、LF、R-R、PNN50%、ASDNN、SDANN、SDNN、rMSSD水平呈正相关（P＜0.05）。结论：CHD患儿经介入封堵术治疗后,血清CRP、NT-proBNP及HRV指标变化明显,与术后NYHA心功能分级显著相关,血清CRP、NT-proBNP及HRV指标有望成为评估CHD患儿介入封堵术后预后的较敏感性指标。     

Circadian rhythm of serum testosterone levels in male beagle dogs--effects of lighting time zone

In a previous study, the author found that serum testosterone (T) levels in male beagle dogs showed a circadian rhythm which was lowest at 12:00, and increased to a peak at 18:00-6:00, thereafter decreasing until 12:00. The reason was thought to be that dogs were breeding under rigid controlled conditions. The present study was performed to investigate the effects of lighting on the circadian rhythm of T level by means of a reversal of the lighting time zone, because lighting is considered an important factor in modulating T levels. Six male beagle dogs of 2 years were used in this study. The routine lighting time (8:00-20:00) and dark time (20:00-8:00) zone in the breeding room was reversed completely and T levels were measured at intervals of 1-5 weeks for up to 54 weeks. Blood samples were collected at 6:00, 12:00, 18:00 and 24:00. The results showed that the circadian rhythm of the T level and the T level at each blood sampling time did not change significantly within 54 weeks. As a result, it was recognized that the circadian rhythm of the T level in male dogs may not be affected by changes in the lighting time zone.     

Improvement in spermatogenic function after subcutaneous implantation of a capsule containing an aromatase inhibitor in four oligozoospermic dogs and one azoospermic dog with high plasma estradiol-17beta concentrations

A capsule containing an aromatase inhibitor (4-androsten-4-ol-3,17-dione) was subcutaneously implanted in four oligozoospermic beagle dogs and one azoospermic beagle dog with high plasma estradiol-17beta (E2) concentrations (15-19 pg/ml) and low plasma testosterone (T) concentrations (0.6-0.8 ng/ml) for 8 weeks and the effect of the aromatase inhibitor on spermatogenic dysfunction was assessed. Plasma E2 and T concentrations and semen quality were examined at 1 week intervals from 3 weeks before to 12 weeks after the start of treatment. Testicular biopsies were done twice (capsule implantation and removal). Plasma E2 concentrations of all dogs decreased (9-14 pg/ml) and plasma T concentrations increased (2.0-2.6 ng/ml) from 3 weeks after capsule implantation to capsule removal. The mean number of spermatozoa ejaculated by all four oligozoospermic dogs between 4 and 9 weeks after implantation was higher (127 x 10(6) to 205 x 10(6)) than before implantation (20 x 10(6) to 38 x 10(6)) (P < 0.05 and 0.01). Very low numbers (2 x 10(4) to 4 x 10(4)) of immotile spermatozoa were observed between 7 and 8 weeks after implantation in the semen collected from the dog with azoospermia. Before implantation, a few spermatozoa were seen in only one-fifth of the seminiferous tubules in this dog; 8 weeks after implantation, the mean diameter and mean number of round spermatids in the seminiferous tubules in all five dogs were higher than before implantation (P < 0.05). Implantation of the capsule containing the aromatase inhibitor in infertile dogs with abnormally high plasma E2 concentrations improved their spermatogenic function, concurrent with decreased plasma E2 and increased plasma T.     

C-reactive protein (CRP) measurement in canine serum following experimentally-induced acute gastric mucosal injury

To establish the diagnostic significance of canine C-reactive protein (CRP) in gastrointestinal disorders, the serum canine CRP concentration was measured in dogs with experimentally-induced acute gastric mucosal injury. Gastric injury was induced in one male and one female beagle by a single dose oral administration of acetylsalicylic acid (200 mg/kg body weight) or indomethacin (60 mg/kg body weight), or sodium chloride (1,000 mg/kg body weight). CRP was measured prior to dose, and 1, 3, 7, and 14 days after the administration of the drugs, together with the total leucocyte counts and serum iron. Changes in the serum CRP in dogs with gastric injury were similar for the three test compounds, and reflected by the endoscopic findings. CRP values increased from 87 to 390 mg/l within 1 to 3 days after the compound administration but returned nearly to the predose levels within 14 days. Endoscopy revealed haemorrhagic erosion of the gastric mucosa in all dogs one day after dosing, with no evidence of the erosions observed after 7 days in many of the dogs. Changes of the total leucocyte and serum iron also occurred following gastric injury, but these changes were not as marked as those observed for CRP. The results of this study suggest that serum CRP level may be a useful indicator of a gastrointestinal mucosal injury in dogs.     

The severity of coronary artery disease and reversible ischemia revealed by N-terminal pro-brain natriuretic peptide in patients with unstable angina and preserved left ventricular function

The association between the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the severity of coronary artery disease (CAD) diagnosed by coronary angiography and other approaches has been investigated. The clinical application of NT-proBNP is restricted by the drawbacks of these techniques now available in screening out patients who need intensive or conservative treatment. Fractional flow reserve (FFR) is superior to coronary angiography and other functional indicators. Accordingly, we designed to investigate the association between NT-proBNP and myocardial ischemia from the perspective of anatomy and physiology in patients with unstable angina and preserved left ventricular function. Plasma samples were collected from 110 patients and NT-proBNP levels were measured by radioimmunoassay. The severity of coronary artery stenosis in patients was measured by coronary angiography and FFR. Stenosis ≥50% in the left main artery or stenosis of 70%, and fractional flow reserve (FFR) ≤0.80 in one or more coronary branches with diameter ≥2 mm were defined as “positive”, which require revascularization. NT-proBNP levels increased progressively between patients with negative and positive angiographic results (p < 0.05), and between FFR-negative and FFR-positive patients (p < 0.05). A significant correlation was observed between log NT-proBNP and log GS (GS = Gensini score, p < 0.001). NT-proBNP level serves as a predictor of positive results of angiographic stenosis and FFR, with the area under the receiver operating characteristic curve being 0.697 and 0.787, respectively. NT-proBNP levels are correlated with the severity of anatomic coronary obstruction and inducible myocardial ischemia, but NT-proBNP per se is insufficient to identify clinically significant angiographic and physiological stenoses.     

Low-dose intravenous nitrite improves hemodynamics in a canine model of acute pulmonary thromboembolism

Acute pulmonary thomboembolism (APT)-induced pulmonary hypertension can be counteracted by activating the nitric oxide (NO)-cGMP pathway. Recent studies have demonstrated that the naturally occurring anion nitrite (NO₂^-) is a bioactive storage reservoir for NO, and is reduced to NO under conditions of hypoxia and acidosis. We hypothesized that nitrite infused intravenously could attenuate the hemodynamic changes associated with APT. APT was induced with autologous blood clots injected into the right atrium in mongrel dogs. After APT (or saline), the dogs received an intravenous nitrite (or saline) infusion (6.75 μmol/kg over 15 min and then 0.28 μmol/kg/min) and hemodynamic evaluations were carried out for 2 h. Plasma nitrite concentrations were measured using ozone-based reductive chemiluminescence methodologies. APT decreased cardiac index (CI) and increased pulmonary vascular resistance index (PVRI); these effects were improved during infusions of sodium nitrite. Accordingly, nitrite infusion increased cardiac index by 28%, reduced the PVRI by 48%, and the systemic vascular resistance index (SVRI) by 21% in embolized dogs, suggesting a greater effect on the ischemic embolized vascular system than the systemic circulation following embolization. Interestingly, in nonembolized control dogs the same nitrite infusion decreased MAP and CI (all P < 0.05). The nitrite infusion increased plasma nitrite concentrations by approximately 2 μM, and produced dose-dependent effects on PVRI, MAP, and SVRI. Remarkably, blood levels of nitrite as low as 500 nM decreased PVRI and SVRI in this model, suggesting a potential role of nitrite in physiological blood flow regulation. These results suggest that a low-dose nitrite infusion produces beneficial hemodynamic effects in a dog model of APT. These findings suggest a new therapeutic application for nitrite and support emerging evidence for a surprisingly potent and potentially physiological vasoactivity of nitrite.     

利伐沙班与华法林对高龄非瓣膜性房颤患者D-二聚体、NT-proBNP水平的影响

目的:探讨利伐沙班与华法林对高龄非瓣膜性房颤(NVAF)患者血浆D-二聚体(D-D)、N末端B型利钠肽原(NT-pro BNP)水平的影响及其临床疗效。方法:选取我院2015年1月~2016年11月收治的146例高龄NVAF患者,采取随机数字表法均分为两组。华法林组予以华法林抗栓治疗,利伐沙班组采取利伐沙班抗栓治疗。记录比较两组治疗期间栓塞、出血情况及不良反应,以及治疗前后血浆D-二聚体(D-D)、N末端B型利钠肽原(NT-pro BNP)水平的变化情况。结果:两组治疗后栓塞发生率比较,差异无统计学意义(P0.05)。利伐沙班组出血发生率(4.1%)低于华法林组(15.1%),差异具有统计学意义(P0.05)。与治疗前相比,两组治疗后血浆D-D和NT-pro BNP水平均降低,差异具有统计学意义(P0.01);治疗后,两组血浆D-D和NT-pro BNP水平比较,差异无统计学意义(P0.05)。两组不良反应发生率对比,差异无统计学意义(P0.05)。结论:与华法林相比,高龄非瓣膜性房颤应用利伐沙班抗栓治疗在患者耐受性与预防血栓栓塞方面优势相当,但利伐沙班更能有效降低患者出血风险。     

Preliminary observations on the association between serum IL-6 and hydration status and cardiovascular risk in patients treated with peritoneal dialysis

IntroductionSystemic inflammation, as defined by elevated blood IL-6, is a strong independent predictor of peritoneal dialysis (PD) patient survival. The present study has aimed to determine whether there exists a particular “phenotype” associated with high systemic IL-6 that characterizes PD patients in terms of their fluid status and cardiac parameters.MethodsFifty-seven prevalent PD patients were classified according to serum concentrations of IL-6. The degree of overhydration was assessed by bioimpedance analysis (BIA). Echocardiography and serum concentrations of NT-proBNP and troponin T were used to assess cardiovascular risk.ResultsPatients with high serum IL-6 were older, more often diabetic, treated with PD for longer, and significantly more overhydrated. There was a significant correlation between serum IL-6, hydration status (r = 0.38; p = 0.002) and serum albumin (r = −0.35; p = 0.009). Multivariate regression analysis confirmed a strong association of overhydration, hypoalbuminemia, and systemic IL-6 concentration. Patients with high IL-6 had significantly increased levels of both NT-proBNP (r = 0.36; p = 0.006) and TnT (r = 0.50; p < 0.001) in the absence of abnormalities in echocardiography.ConclusionsHigh systemic IL-6 identifies PD patients with increased cardiovascular risk that is significantly related to overhydration. Thus, the measurement of serum IL-6 may contribute to the more accurate assessment of cardiovascular status in patients undergoing PD.     

参附注射液对老年慢性心衰患者血清NT-proBNP、H-FABP及CRP 水平的影响

目的:探讨参附注射液对老年慢性心衰患者脑钠肽(NT-proBNP)、心脏型脂肪酸结合蛋白(H-FABP)及C-反应蛋白(CRP)的影响。方法:收集我院收治的慢性心力衰竭患者70例,随机分为对照组和实验组,每组各35例,对照组患者均给予相应常规对症治疗,实验组患者在对照组基础上给予参附注射液静脉滴注,治疗结束后观察并比较两组患者治疗前后血清NT-proBNP、H-FABP及CRP水平的变化以及治疗效果。结果:与治疗前相比,两组患者治疗后血清NT-proBNP、H-FABP及CRP水平与治疗前相比均降低(P0.05);实验组患者治疗后血清NT-proBNP、H-FABP及CRP水平与对照组患者相比较低(P0.05)。实验组临床总有效率与对照组相比较高,但差异无统计学意义(P0.05)。结论:参附注射液能够降低老年慢性心衰患者血清NT-proBNP、H-FABP及CRP水平,提高临床疗效。     

Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway

Increase of myocardial oxidative stress is closely related to the occurrence and development of cardiac hypertrophy. Cordycepin, also known as 3'‐deoxyadenosine, is a natural bioactive substance extracted from Cordyceps militaris (which is widely cultivated for commercial use in functional foods and medicine). Since cordycepin suppresses oxidative stress both in vitro and in vivo, we hypothesized that cordycepin would inhibit cardiac hypertrophy by blocking oxidative stress‐dependent related signalling. In our study, a mouse model of cardiac hypertrophy was induced by aortic banding (AB) surgery. Mice were intraperitoneally injected with cordycepin (20 mg/kg/d) or the same volume of vehicle 3 days after‐surgery for 4 weeks. Our data demonstrated that cordycepin prevented cardiac hypertrophy induced by AB, as assessed by haemodynamic parameters analysis and echocardiographic, histological and molecular analyses. Oxidative stress was estimated by detecting superoxide generation, superoxide dismutase (SOD) activity and malondialdehyde levels, and by detecting the protein levels of gp91^phox and SOD. Mechanistically, we found that cordycepin activated activated protein kinase α (AMPKα) signalling and attenuated oxidative stress both in vivo in cordycepin‐treated mice and in vitro in cordycepin treated cardiomyocytes. Taken together, the results suggest that cordycepin protects against post‐AB cardiac hypertrophy through activation of the AMPKα pathway, which subsequently attenuates oxidative stress.     

Effects of praeruptorin C on blood pressure and expression of phospholamban in spontaneously hypertensive rats

BackgroundThe traditional Chinese medicine Praeruptorin c (Pra-c) has many physiological and pharmacological effects, including antagonistic effects on blood pressure and calcium levels, maintenance of cellular calcium homeostasis, and improved cardiac systolic and diastolic function. It is potentially a novel and versatile drug for the treatment and prevention of cardiovascular diseases.ObjectiveTo explore the possible impact of Pra-c on blood pressure in SHR and its mechanism of action.Materials and methodsTwenty SHR were randomly divided into a Pra-c group [Pra-c was administered intragastrically, 20 mg kg⁻¹ d⁻¹, n = 10] or an untreated control group (n = 10), containing 10 age-matched SD rats. Each group of rats was followed for 8 weeks. Before and during the treatment, tail artery systolic blood pressure was measured using a tail-cuff every 2 weeks. After 8 weeks, the rats were sacrificed and RNA was extracted from homogenates of cardiac tissue. Tissue from the left ventricle was fixed, sectioned and H&E stained to assess possible changes in myocardial cell structure and morphology. Semi-quantitative RT-PCR was used to assess changes in phospholamban gene expression in treated and untreated rats.ResultsSHR treated with Pra-c for 8 weeks had a lower systolic pressure than untreated SHR (p < 0.05), two measures of cardiac damage, the heart mass index and left ventricle mass index (HMI and LVMI, respectively) were improved, and the level of PLB mRNA expression was lower in the untreated SHR group (p < 0.05).Discussion and conclusionWith continuous hypertension, SHR gradually formed or developed cardiac hypertrophy and fibrosis. Pra-c had a clear effect on blood pressure in SHR, and reversed SHR ventricular remodeling by upregulating the gene expression of sarcoplasmic reticulum PLB.     

Effects of Transport Stress on Serum Alkaline Phosphatase Activity in Beagle Dogs

Here, to determine the effects of transport stress on blood parameters in dogs, we investigated the changes in hematologic and serum chemical parameters in healthy beagle dogs transported from Beijing, China, to Osaka, Japan, to obtain the background data. Only the activity of serum alkaline phosphatase increased clearly upon arrival, a change attributed to transport stress, but the activity gradually reduced afterward. No marked changes in levels of other blood parameters were noted. Our findings here suggest that alkaline phosphatase is a useful tool for studying transport stress.     

Evaluation of a spontaneous canine model of immunoglobulin E-mediated food hypersensitivity: dynamic changes in serum and fecal allergen-specific immunoglobulin E values relative to dietary change

The purpose of the pilot study reported here was to evaluate serum and fecal total and allergen-specific immunoglobulin E (IgE) responses to dietary change in five Maltese x beagle dogs with suspected food hypersensitivity, compared with those of five clinically normal dogs. Clinical parameters (pruritus, otitis, and diarrhea) improved in the Maltese x beagle dogs during feeding of a novel diet, and signs were exacerbated by oral allergen provocation. Relative concentrations of serum and fecal wheat-, corn-, and milk-specific IgE were determined by use of an ELISA. The onset of clinical signs of disease was accompanied by an increase in serum allergen-specific IgE concentrations. In contrast, changes in clinical signs of disease or allergen-specific IgE values were not seen in the control group undergoing the same regimen. Total serum IgE concentration was measured by use of the ELISA, and comparison with known quantities of a monoclonal IgE allowed absolute values to be reported. Values were high in the Maltese x beagle colony (7 to 34 microg/ml), compared with those in the control dogs (0.7 to 6 microg/ml). Total serum and total fecal IgE concentrations did not change in either group during the study. Although allergen-specific IgE was detected in the feces of both groups, significant interassay variability made interpretation of the results difficult. The authors concluded that these Maltese x beagle dogs satisfied the currently recognized clinical criteria for the diagnosis of canine food hypersensitivity. Furthermore, the clinical and serologic responses seen in these dogs in response to oral allergen provocation suggest that this may be a useful model for the study of spontaneous food hypersensitivity.