Expression and modulation of connective tissue growth factor in renal interstitial fibrosis

CTGF, a member of the CCN family of immediate early genes, is a recently discovered profibrotic growth factor, which is involved in many pathophysiologic procedures. CTGF acts as a downstream effector of TGF-β acting on interstitial cells to enhance the progression of fibrotic renal diseases. It has been shown that CTGF gene expression can be induced or blocked by some kinds of cytokine and drugs. It is an interesting candidate target for future intervention strategies of renal interstitial fibrosis.     

Influence of paricalcitol on renal tubulointerstitial fibrosis in diabetic nephropathy

AIM: To investigate the effect of paricalcitol (P) on renal tubulointerstitial fibrosis and the underlying mechanisms in diabetic nephropathy (DN).METHODS: DN rat model was induced by a single intraperitoneal injection of streptozotocin after fasting. The animals were randomly divided into 2 groups:the DN rats in paricalcitol-intervened group (group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4 μg/kg (3 times a week); the DN rats in DN group (group D) were given isopyknic propylene glycol. Normal control group (group C) was also set up. The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks. The biochemical indexes were measured. The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4, β-catenin and Klotho by immunohistochemistry and Western blotting. In addition, the correlation among the above indexes was analyzed.RESULTS: (1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D (P<0.05). (2) The area of renal tubulointerstitial fibrosis increased in group D compared with group C, while decreased in group P compared with group D (P<0.05). (3) The expression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05). Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 and β-catenin decreased in group P (P<0.05). (4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 and β-catenin (P<0.05).CONCLUSION: Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.     

Echocardiography and conventional Doppler examination in clinically healthy adult Cavalier King Charles Spaniels: Effect of body weight,age, and gender,and establishment of reference intervals

ObjectivesThe objectives of this study were (1) to assess the potential effect of body weight (BW), age, and gender on the most commonly used echocardiographic and conventional Doppler variables in a large population of healthy Cavalier King Charles Spaniels (CKCS), and (2) to establish the corresponding reference intervals (RI).Animals134 healthy adult CKCS.MethodsUltrasound examinations were performed by trained observers in awake dogs. M-mode variables included left ventricular (LV) end-diastolic and end-systolic diameters, LV free wall and interventricular septal thicknesses at end-diastole and end-systole, and LV fractional shortening (FS%). The left atrium (LA) and aortic (Ao) diameters were measured using a 2D method, and the LA/Ao was calculated. Pulsed-wave Doppler variables included peak systolic aortic and pulmonary flow velocities, mitral E and A waves, and E/A ratio. Effects of BW, age, and gender on these 15 variables were tested using a general linear model, and RIs were determined by applying the statistical procedures recommended by the Clinical and Laboratory Standards Institute.ResultsA significant BW effect was observed for all variables, except LA/Ao, FS%, and mitral E/A ratio. A significant but negligible effect of gender and age was also observed for 5/15 and 4/15 of the tested variables, respectively. Only the BW effect on M-mode variables was considered as clinically relevant and the corresponding regression-based RIs were calculated.ConclusionsBody weight should be taken into account when interpreting echocardiographic values in CKCS, except for LA/Ao, FS%, and mitral E/A ratio.     

药用真菌双向固体发酵草乌后菌质对小鼠的急性毒性及致大鼠心律失常作用

[目的]研究药用真菌灵芝、茯苓、红栓菌和扇菇菌运用双向固体发酵草乌后菌质(分别称为灵乌菌质、茯乌菌质、栓乌菌质和扇乌菌质)对小鼠的急性毒性作用和对大鼠心脏毒性的影响.[方法]运用双向发酵技术获得菌质,根据急性毒性预试验结果进行最大耐受量试验,采用Powerlab生理信号记录系统,通过观察大鼠Ⅱ导联心电图变化研究不同药物对大鼠的心脏毒性.[结果]相同剂量下灌胃给药,在给药7d后各处理组小鼠体重增长明显低于正常对照组;给药14 d后,灵乌菌质组体重增长很快,接近于正常对照组;与炮制品组相比,灵乌菌质组、扇乌菌质组和栓乌菌质组对大鼠心律失常发生次数有显著性降低作用(P ＜0.05或P＜0.01),而茯乌菌质组对大鼠心律失常的影响和炮制品组没有显著差异;各发酵组间没有显著差异.[结论]灵乌菌质、扇乌菌质和栓乌菌质具有降低心律失常发生率的作用.     

Papillary muscle measurements in cats with normal echocardiograms and cats with concentric left ventricular hypertrophy

BACKGROUND: Papillary muscle hypertrophy can occur in conjunction with, or as the only indication of, hypertrophic cardiomyopathy or other diseases that result in left ventricular concentric hypertrophy (LVCH). Assessment of papillary muscle size is usually subjective because objective measures have not been reported. HYPOTHESIS: The study hypothesis was that papillary muscle dimensions are different between normal cats and cats with LVCH. ANIMALS: Echocardiograms from 44 normal cats and 40 cats with LVCH were included in the study. METHODS: All measurements were taken from the right parasternal short-axis view at the level of the papillary muscles at end-diastole. Three methods were used to assess papillary muscle size: the area subtraction method, the direct area trace method, and the diameter method. Measurements were compared between cat groups and method comparisons were made among methods for area determination. RESULTS: Cats with LVCH were older and had significantly greater left ventricular septal and free wall thicknesses and larger left atrial measurements than normal cats (P < .0006). Papillary muscle measurements were significantly greater by all measurement methods in cats with LVCH than in cats with normal echocardiograms (P < .0001). The area subtraction method and direct area trace method showed moderate agreement. CONCLUSIONS AND CLINICAL IMPORTANCE: Papillary muscle measurements were larger for LVCH cats than normal cats; however, some overlap was present. The establishment of these objective measures adds to the echocardiographic examination of cats.     

Cardiovascular effects of acute pulmonary obstruction in horses with recurrent airway obstruction

BACKGROUND: Recurrent airway obstruction (RAO) is common in horses. Although pulmonary artery (PA) pressure increases during RAO, cardiac function in horses with RAO has received limited attention. HYPOTHESIS: The purpose of this study was to noninvasively determine the cardiovascular effects of acute pulmonary obstruction (APO) in horses with RAO and their reversibility. ANIMALS: Five geldings with RAO, inducible by exposure to moldy hay, were studied. METHODS: Pulmonary mechanics, echocardiography, serum troponin I concentrations, arterial blood gases, and hematocrit were obtained before and after 7 days of APO. Heart rate, PA diameter and flow characteristics, right and left ventricular luminal dimensions and wall thicknesses, global cardiac performance, and evidence of myocardial damage were evaluated. Pulmonary mechanics and echocardiography were reevaluated during remission. RRESULTS: Severe, transient APO did not induce chronic cor pulmonale in horses, because cardiac anatomy and function were normal between episodes. An acute episode of APO produced anatomical and functional cardiac changes in both the right and left heart (including increased PA diameter, abnormal septal motion, and decreased left ventricular diameter and estimated stroke volume), possibly because of the development of pulmonary hypertension, without apparent myocardial damage. The decrease in stroke volume was offset by the increase in heart rate. CONCLUSIONS AND CLINICAL IMPORTANCE: With APO of 7 days' duration, cardiovascular abnormalities and the functional airway changes that produce them are reversible when the offending allergens are removed.