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Interstitial Fibrosis (interstitial + fibrosis)
Selected AbstractsImpact of Subclinical Inflammation on the Development of Interstitial Fibrosis and Tubular Atrophy in Kidney Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010R. L. Heilman Our aim was to study the impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy (IF/TA) on a 1-year protocol biopsy in patients on rapid steroid withdrawal (RSW). A total of 256 patients were classified based on protocol biopsy findings at months 1 or 4. Group 1 is 172 patients with no inflammation, group 2 is 50 patients with subclinical inflammation (SCI), group 3 is 19 patients with subclinical acute rejection (SAR) and group 4 is 15 patients with clinical acute rejection (CAR). On the 1-year biopsy, more patients in group 2 (SCI) (34%, p = 0.004) and group 3 (SAR) (53%, p = 0.0002), had an IF/TA score > 2 compared to group 1 (control) (15%). IF/TA was not increased in group 4 (CAR) (20%). The percent with IF/TA score > 2 and interstitial inflammation (Banff i score > 0) was higher in group 2 (16%, p = 0.004) and group 3 (37%, p < 0.0001) compared to group 1 (3%). In a multivariate analysis, patients in groups 2 or 3 had a higher risk of IF/TA score > 2 on the 1-year biopsy (OR 6.62, 95% CI 2.68,16.3). We conclude that SCI and SAR increase the risk of developing IF/TA in patient on RSW. [source] Characterization of the Electroanatomic Substrate for Monomorphic Ventricular Tachycardia in Patients with Nonischemic CardiomyopathyPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 7 2002HENRY H. HSIA HSIA, H.H., et al.: Characterization of the Electroanatomic Substrate for Monomorphic Ventricular Tachycardia in Patients with Nonischemic Cardiomyopathy. Ventricular arrhythmias are common in the setting of nonischemic cardiomyopathy. The etiology for the cardiomyopathy is frequently not identified and the label of "idiopathic" is applied. Interstitial fibrosis with conduction system involvement and associated left bundle branch block characterizes the disease process in some patients and the mechanism for monomorphic ventricular tachycardia is commonly bundle branch reentry. However, most patients with nonischemic cardiomyopathy have VT due to myocardial reentry and demonstrate marked myocardial fibrosis and electrogram abnormalities. Although patient specific, the overall distribution of electroanatomic abnormalities appears to be equal on the endocardium and epicardium. The extent of electrogram abnormalities appears to parallel arrhythmia presentation and/or inducibility. Patients with sustained uniform morphology VT have the most extensive endocardial and epicardial electrogram abnormalities. Magnetic electroanatomic voltage mapping provides a powerful tool to characterize the location and extent of the arrhythmia substrate. Basal left ventricular myocardial involvement, as indexed by the location of contiguous electrogram abnormalities, is common in patients with sustained VT and left ventricular cardiomyopathy. The relatively equal distribution of electrogram abnormalities on the endocardium and epicardium, and the results of mapping and ablation attempts, suggest that critical parts of the reentrant circuit may be epicardial. Unique features of the electroanatomic substrate associated with cardiomyopathy due to Chagas' disease, sarcoidosis, and arrhythmogenic right ventricular dysplasia are also discussed. [source] HISTOPATHOLOGICAL AND SCINTIGRAPHIC COMPARISONS OF THE PROTECTIVE EFFECTS OF l -CARNITINE AND AMIFOSTINE AGAINST RADIATION-INDUCED LATE RENAL TOXICITY IN RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2009Murat Caloglu SUMMARY 1The aim of the present study was to compare the protective effects of l -carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., l -carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., l -carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (Tmax) and time from peak count to half count (T˝) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T˝ of the right kidney was 8 ± 2 and 21 ± 2 min, respectively. The Tmax values for the AMI + RAD and LC + RAD groups (2.8 ± 0.2 and 3.2 ± 0.2 min, respectively) were similar to those in the control group (2.5 ± 0.3 min). 4Based on the results of the present study, l -carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity. [source] Effect of tributyltin on testicular development in Sebastiscus marmoratus and the mechanism involved,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2009Jiliang Zhang Abstract Organotin compounds, such as tributyltin (TBT), that have been used as antifouling biocides can induce masculinization in female mollusks. However, few studies addressing the effects of TBT on fishes have been reported. The present study was conducted to investigate the effects of TBT at environmentally relevant concentrations (1,10, and 100 ng/L) on testicular development in Sebastiscus marmoratus and to gain insight into its mechanism of action. After exposure for 48 d, the gonadosomatic index had decreased in a dose-dependent manner. Although the testosterone levels in the testes were elevated and the 17,-estradiol levels were decreased, spermatogenesis was suppressed. Moreover, ,-glutamyl transpeptidase activity (which is used as a Sertoli cell marker) was decreased in a dose-dependent manner after TBT exposure, and serious interstitial fibrosis was observed in the interlobular septa of the testes in the 100 ng/L TBT test group. Increases in the retinoid × receptors and peroxisome proliferator activated receptor , expression and the progressive enlargement of lipid droplets in the testes were observed after TBT exposure. Estrogen receptor , levels in the testes of the fish exposed to TBT decreased in a dose-dependent manner. The reduction of estrogen receptor , mRNA resulted from the decrease of 17,-estradiol levels, and the progressive enlargement of lipid droplets may have contributed to the dysfunction of the Sertoli cells, which then disrupted spermatogenesis. [source] Correlation of ,-skeletal actin expression, ventricular fibrosis and heart function with the degree of pressure overload cardiac hypertrophy in ratsEXPERIMENTAL PHYSIOLOGY, Issue 3 2006Donatella Stilli We have analysed alterations of ,-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, and invasive haemodynamic measurements were performed in anaesthetized animals. After killing, subgroups of AC and C rats were used to evaluate in the left ventricle the expression and spatial distribution of ,-skeletal actin and the amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic pressure, ventricular weight and ventricular wall thickness. AC0.7 and AC0.4 rats also showed a larger amount of fibrosis and upregulation of ,-skeletal actin expression associated with a higher vulnerability to ventricular arrhythmias (AC0.7 and AC0.4) and enhanced myocardial contractility (AC0.4). Our results illustrate the progressive changes in the extracellular matrix features accompanying early ventricular remodelling in response to different degrees of pressure overload that may be involved in the development of cardiac electrical instability. We also demonstrate for the first time a linear correlation between an increase in ,-skeletal actin expression and the degree of compensated cardiac hypertrophy, possibly acting as an early compensatory mechanism to maintain normal mechanical performance. [source] Long-term evolution of the acute tubular necrosis (ATN) induced by glycerol: role of myofibroblasts and macrophagesINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2002Telma J. Soares Summary. Late structural changes such as interstitial fibrosis in the renal cortex and tubular atrophy have been detected after severe acute tubular necrosis (ATN). The aim of this study was to investigate the expression of fibronectin, ,-smooth muscle actin and macrophages during the evolution of the ATN induced by glycerol and their relationship with the late structural changes observed in the kidneys of these animals. Forty-nine male Wistar rats were injected with a 50% glycerol solution, 8 mL/kg (4 mL/kg applied i.m. to each hind leg) and 14 with 0.15 m NaCl solution. Before glycerol injection on day 1, water was removed for 17 h. Blood and urine samples were collected 1 day after the injection to quantify sodium and creatinine. The animals were killed 5, 30 and 60 days after the injections and the kidneys removed for histological and immunohistochemical studies. The results of the histological and immunohistochemical studies were scored according to the extent of lesion or staining in the cortical tubulointerstitium, respectively. The percentage of tubulointerstitial lesions was determined by morphometry. Glycerol-injected rats presented a transitory increase in plasma creatinine levels and in fractional sodium excretion. The immunohistochemical studies showed increased fibronectin, ,-smooth muscle actin (,-SM-actin), TGF-, and ED-1 (macrophages) staining in the renal cortex from rats killed 5, 30 and 60 days after glycerol injection (P < 0.05) compared to control. The animals killed on day 30 and 60 also presented chronic lesions (fibrosis, tubular dilatation and atrophy) in the renal cortex, despite the recovery of renal function. Macrophages, TGF-, and myofibroblasts may have contributed to the development of renal fibrosis in these rats. [source] Histological study of fetal kidney with urethral obstruction and vesicoureteral reflux: A consideration on the etiology of congenital reflux nephropathyINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2003KENJI SHIMADA Purpose: A recent subject of interest regarding reflux nephropathy is the presence of renal abnormalities in neonates and infants who have no history of urinary tract infections. Debates have centered on the etiology of this renal abnormality , congenital reflux nephropathy; regarding whether it is the result of abnormal ureteral budding or of back pressure effect from sterile reflux. We examined the renal pathology of fetuses with urethral obstruction and vesicoureteral reflux, and we suggest herein a possible etiology of congenital reflux nephropathy. Methods: The renal pathology of seven autopsied fetuses with vesicoureteral reflux was studied. Reflux was demonstrated at autopsy by slow injection of contrast medium into the bladder. Severe urethral obstruction, either atresia or urethral valves, was evident in six of the subjects. Results: In six subjects, abnormality of the urinary tracts was detected by prenatal ultrasonography. Of these six subjects, three revealed characteristics of prune belly syndrome. Reflux was graded as moderate in five subjects, and severe in two. In three subjects autopsied at 21 weeks gestation or earlier, the kidneys were well-developed with normal corticomedullary configuration, and nephrogenesis was retained. In three cases autopsied at over 25 weeks of gestation, the kidneys were grossly cystic, and the nephrogenic zone was completely absent. Contrast medium was observed not only in the dilated ducts and tubules, but also in the subcapsular cysts. Extravasation of the contrast medium was seen in the peritubular space. In the last subject with normal lower urinary tract, abnormal segments among normal cortical structures were observed. Conclusion: Our findings of renal pathology in fetuses with reflux are quite similar to those seen in fetal hydronephrosis. Back pressure from reflux probably damages the developing kidney leading to a degeneration of the ampullae and a reduction in the number of nephrons. Both dilatation of the collecting ducts and tubules, and extravasation of the urine may result in interstitial fibrosis. We postulate that one of the important etiologies of congenital reflux nephropathy may be the result of back pressure from sterile reflux. [source] Combined pulmonary toxicity of cadmium chloride and sodium diethyldithiocarbamateJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2001Erzsébet Tátrai Abstract The pulmonary toxicity of sodium diethyldithiocarbamate and cadmium chloride, each separately and in combination, was compared in Sprague-Dawley rats after single intratracheal instillation in sequential experiments by chemical, immunological and morphological methods. With combined exposure, the cadmium content of the lungs increased permanently relative to that of the lungs of just cadmium-treated animals. Immunoglobulin levels of the whole blood did not change, whereas in bronchoalveolar lavage the IgA and IgG levels increased significantly. Morphological changes were characteristic of the effects of cadmium but were more extensive and more serious than in the case of cadmium administration alone: by the end of the first month, interstitial fibrosis, emphysema and injury of membranes of type I pneumocytes developed and hypertrophy and loss of microvilli in type II pneumocytes were detectable. These results showed that although dithiocarbamates as chelating agents are suitable for the removal of cadmium from organisms, they alter the redistribution of cadmium within the organism, thereby increasing the cadmium content in the lungs, and structural changes are more serious than observed upon cadmium exposure alone. Copyright © 2001 John Wiley & Sons, Ltd. [source] Does Repair of Mitral Regurgitation Eliminate the Need for Left Ventricular Volume Reduction?JOURNAL OF CARDIAC SURGERY, Issue 2003Akira T. Kawaguchi M.D. Methods: Among patients undergoing PLV, 120 had paired pre- and postoperative (<1 week) Doppler echocardiograms. Effects of preoperative MR were studied by comparing 45 patients with no preoperative MR (MR,) and 75 patients with significant MR (MR+; MR = 1.51 when MR is enumerated as none = 0, mild = 1, moderate = 2). Results: MR, patients as compared with the MR+ group were older (53.8 vs. 49.2 years, P = 0.047), had less frequent dilated cardiomyopathy (33.3% vs 49.3%,P <0.01), similar ventricular dimension (72.3 mm vs 73.0 mm), septal thickness (9.5 mm vs 9.6 mm), posterior wall, fractional shortening (15.9% vs 16.8%) and ventricular mass (330 g vs 345 g), resulting in comparably reduced functional capacity (NYHA 3.40 vs 3.67). Although the MR, group required significantly less frequent mitral procedure (64.4% vs 84.0%, P < 0.01) and shorter cardiac arrest time, they had similar postoperative MR (0.22 vs 0.39), highly significant parallel reduction in ventricular dimension (P < 0.001 in either group), and improved %FS (P <0.001 in either group), resulting in similar hospital survival (87.1% vs 86.4%) and 90-day survival (71.1% vs 78.7%) with significantly comparable improvement in functional class (P = 0.011 in both groups). Histological severity of interstitial fibrosis (P = 0.80), weight (P = 0.93), and thickness (P = 0.76) of excised myocardium was comparable between the two groups. Conclusion: Patients with no preoperative MR were found to benefit from PLV as did patients with significant MR. Beneficial effects of PLV appeared to derive mainly from volume reduction rather than abolished MR in this study.(J CARD SURG 2003;18 (Suppl 2):S95-S100) [source] Age-Related Increase in Atrial Fibrillation Induced by Transvenous Catheter-Based Atrial Burst Pacing: An In Vivo Rat Model of Inducible Atrial FibrillationJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2010DONGZHU XU M.D. AF Rat Model Induced by Transvenous Catheter Pacing.,Introduction: Large animal models of atrial fibrillation (AF) are well established, but limited experimental reports exist on small animal models. We sought to develop an in vivo rat model of AF using a transvenous catheter and to evaluate the model's underlying characteristics. Methods and Results: Echocardiogram, surface electrocardiogram (ECG), and atrial effective refractory period (AERP) were recorded at baseline in young (3 months) and middle-aged (9 months) Wistar rats. AF inducibility and duration were measured through transvenous electrode catheter in young (n = 11) and middle-aged rats (n = 11) and middle-aged rats treated with either pilsicainide (1 mg/kg iv, n = 7) or amiodarone (10 mg/kg iv, n = 9). Degrees of interstitial fibrosis and cellular hypertrophy in the atria were assessed histologically. The P-wave duration and AERP were significantly longer and echocardiographic left atrial dimension significantly larger in middle-aged versus young rats. AF was inducible in >90% of all procedures in both untreated rat groups, whereas AF inducibility was reduced by the antiarrhythmic drugs. The AF duration was significantly longer in middle-aged than in young rats and was significantly shortened by treatment with either pilsicainide or amiodarone. Histologic analysis revealed significant increases in atrial interstitial fibrosis and cellular diameter in middle-aged versus young rats. Conclusions: Transvenous catheter-based AF is significantly longer in middle-aged than in young rats and is markedly reduced by treatment with antiarrhythmic drugs. This rat model of AF is simple, reproducible, and reliable for examining pharmacologic effects on AF and studying the process of atrial remodeling.(J Cardiovasc Electrophysiol, Vol. 21, pp. 88,93, January 2010) [source] Enalapril Preserves Sinus Node Function in a Canine Atrial Fibrillation Model Induced by Rapid Atrial PacingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2005MASAO SAKABE M.D. Effects of enalapril on canine sinus node (SN) dysfunction induced by long-term rapid atrial pacing were investigated. Methods and Results: Seventeen beagles were pretreated with either placebo (group I, n = 9) or enalapril 1 mg/kg/day (group II, n = 8) and paced at 500/min from the right atrial appendage for 4 weeks. Every week, corrected sinus node recovery time (CSNRT) and sinus cycle length (SCL) were measured. Quantitative analysis of interstitial fibrosis (IF) and adipose tissue (AT) in the SN was performed with Masson's trichrome stain, and apoptosis of the sinus nodal cells were detected with terminal deoxynucleotidyl transferase nick end-labeling. In group I, rapid atrial pacing prolonged both CSNRT and SCL. After 4 weeks of pacing, CSNRT and SCL were significantly shorter in group II (CSNRT, 410 ± 37 msec; SCL, 426 ± 34 msec) than in group I (CSNRT, 717 ± 52 msec, P < 0.005; SCL, 568 ± 73 msec, P < 0.05). Both IF and AT of the SN were greater in group I (IF, 9.7 ± 1.9%; AT, 32.6 ± 5.9%) than in seven sham dogs (IF, 2.4 ± 0.9%, P < 0.05; AT, 4.0 ± 1.7%, P < 0.05) and in group II dogs (IF, 4.0 ± 2.0%, P < 0.05; AT, 4.0 ± 1.7%, P < 0.05). End-labeling assay was positive in three of nine dogs in group I, but negative in group II and sham dogs. Conclusions: Rapid atrial pacing impaired SN function through IF and AT of the SN. Enalapril prevented these pacing-induced degenerative changes and improved SN function. [source] An Autopsy Case of Brugada Syndrome with Significant Lesions in the Sinus NodeJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2005SHIN-ICHIRO MORIMOTO M.D. A 30-year-old man with Brugada syndrome died suddenly. The heart weighed 380 g. The left ventricular wall showed mild thickening, and marked fatty tissue deposition was noted in the right ventricular outflow tract. Neither ventricle was enlarged. Contraction band necrosis was diffuse in both ventricles. In the ventricles no cardiac muscle cell hypertrophy or atrophy, or significant interstitial fibrosis was observed. In the sinus node the number of nodal cells was reduced by half, with fatty tissue and fibrosis prominent. But no lesions were evident in the right bundle branch. [source] Aging-Related Increase to Inducible Atrial Fibrillation in the Rat ModelJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002HIDEKI HAYASHI M.D. Aging and Atrial Fibrillation.Introduction: Aging is associated with atrial interstitial fibrosis and increased incidence of atrial fibrillation (AF). We hypothesized that aged rats are suitable for study of aging-related AF and that partial atrial cellular uncoupling induced with heptanol in young rats mimics aging-related AF. Methods and Results: Interatrial conduction time and atrial response to burst atrial pacing were evaluated in 11 young (2,3 months) and 12 old (22,24 months) male rats (Fisher 344) in the Langendorff-perfused setting. At baseline, sustained (>30 sec) atrial tachycardia (AT) and AF were induced in 10 of 12 and in 7 of 12 old rats, respectively. No such arrhythmias could be induced in the young rats. Old rats had significantly (P < 0.01) longer interatrial conduction time and P wave durations than the young rats. Burst pacing failed to induce AT and AF in all 11 young rats studied. The effects of heptanol 2 to 10 ,M were studied in both groups. Heptanol 2 to 5 ,M promoted inducible AT in all 5 young rats studied; however, when its concentration was raised to 10 ,M, AT could no longer be induced in any of the 5 young rats. No AF could be induced in any of the 5 young rats at heptanol concentrations of 2 to 10 ,M. In the old rats, AF could still be induced during perfusion of 2 ,M heptanol. However, when its concentration was raised to 5 and 10 ,M, AF could not be induced in any of the 6 old rats studied. Optical mapping using a potentiometric dye showed a periodic single wavefront of activation during AT in both groups and 2 to 4 independent wavefronts propagating in different directions during AF in the old rats. Histology revealed a significant increase in interstitial atrial fibrosis (P < 0.01), atrial cell size (P < 0.05), and heart weight in old versus young rats. Fibrosis in the old rats was highly heterogeneous. Conclusion: The rat model is suitable for study of aging-related AF. Uniform partial atrial cellular uncoupling with heptanol perfusion in the young rats, although promoting inducible AT, does not mimic aging-related AF. The results suggest that heterogeneous atrial interstitial fibrosis and atrial cell hypertrophy might contribute to the aging-related increase in atrial conduction slowing, conduction block, and inducible AF in the old rat model. [source] Renal cortex remodeling in nitric oxide deficient rats treated with enalaprilJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004Noemi Barbuto Abstract The kidney NO synthase is one of the most important renal controlling systems. This paper aims the quantification of renal cortical components involved in blood pressure regulation under NOs blockade. Spontaneous hypertensive rats (SHRs) are submitted to chronic blockade of NOs by L-nitro-arginine-methyl-ester (L-NAME) and an ACE inhibitor (enalapril) in comparison with the normotensive Wistar rats. Twenty SHRs and 5 Wistar rats were divided in 5 groups and observed for 21 days for blood pressure (BP) and serum creatinine: control Wistar (5) (C-W), control SHR (5) (C-SHR), L-SHR (5) - received L-NAME 30 mg/kg/day, L+E-SHR (5) - received L-NAME and Enalapril maleate 15 mg/kg/day, E-SHR (5) - received Enalapril maleate. A quantitative morphometric study (glomerular density, QA[g1], interstitium volume density, Vv[i], tubular surface and length densities, Sv[t] and Lv[t]) were performed at the end. The BP reached 226±15 mmHg in L-SHR group. The BP difference between the L-SHR and the C-SHR groups was significant from the first week while the E-SHR group became significant from the second week. At the end of the experiment the BP of the E-SHR group was similar to the BP in the C-W group. The QA[g1] was similar among C-SHR, L-SHR and L+E-SHR groups and no difference was found between E-SHR and C-W groups. In the L-SHRs serum creatinine was greatly increased, and microscopy showed thickening of arteriolar tunica media with an increase of the wall-to-lumen ratio, perivascular fibrosis, inflammatory infiltrated, tubular atrophy and interstitial fibrosis with focal segmental glomerulosclerosis. The use of enalapril was not completely efficient in reducing BP and morphological injury when the hypertension of SHRs was increased with the NOs blockade suggesting that NO deficiency-induced hypertension is not entirely mediated by the RAAS. [source] Beneficial effect of enalapril in spontaneously hypertensive rats cardiac remodeling with nitric oxide synthesis blockadeJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2002R. L. de Andrade Zorzi Abstract Aims. To study the efficiency of an angiotensin converting enzyme inhibitor on the blood pressure (BP) and the myocardium remodeling when spontaneously hypertensive rats (SHRs) are submitted to nitric oxide synthesis (NOs) blockade (with L-NAME) and simultaneously treated. Methods. Young adult male SHRs were separated in four groups (n = 5) and treated for 20 days: Control, L-NAME, L-NAME+Enalapril, and Enalapril. The alterations of the BP, heart mass/body mass ratio and stereological parameters for myocytes, connective tissue and intramyocardial vessels were studied among the groups. Results. The SHRs with NOs blockade showed a great modification of the myocardium with extensive areas of reparative and interstitial fibrosis and accentuated hypertrophy of the cardiac myocytes (cross sectional area 60% higher in animals taking L-NAME than in Control SHRs). Comparing the SHRs with NO deficiency (L-NAME group), the Control SHRs and the Enalapril treated SHRs significant differences were found in the BP and in all stereological parameters. The NO deficiency caused an important BP increment in SHRs that was partially attenuated by Enalapril. This Enalapril effect was more pronounced in Control SHRs. A significant increment of the intramyocardial vessels was observed in NO deficient SHRs and Control SHRs treated with Enalapril demonstrated by the stereology (greater microvascular densities in treated SHRs). Conclusion. Enalapril administration showed a beneficial effect on vascular remodeling and myocardial hypertrophy in SHRs. In SHRs with NO blockade, however, the beneficial effect of Enalapril occurred only in vascular remodeling. [source] Decorin transfection in human mesangial cells downregulates genes playing a role in the progression of fibrosisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 4 2002Antonia Costacurta Abstract The proteoglycan decorin inhibits TGF-,; therefore, it could antagonize progression of fibrotic diseases associated with activation of TGF-,1. The effect of decorin transfection in human mesangial cells (HMCs) on the expression of genes related to kidney fibrosis was investigated. HMCs, isolated from glomeruli of healthy portions of human kidneys removed due to carcinoma, were histochemically typed. Decorin cDNA cloned in a eukaryotic expression vector was transfected into HMCs. Gene expression of fibrogenetic cytokines and fibrotic proteins TGF-,1, PDGF-,, ,1 collagen type IV, ,1 collagen type I, fibronectin, and tenascin was analyzed, by reverse transcription polymerase chain reaction (RT-PCR), 24 hr after transfection. Immunoblotting analysis of protein extracts using anti-decorin IgG, revealed a positive signal of about 52 MDa, corresponding to the molecular weight of decorin, in cultures transfected with the decorin gene. Decorin mRNA increased about 12 times in cultures transfected with the construct pCR3.1-Deco. Cells with increased decorin synthesis showed a 61% decrease of TGF-,1 mRNA, a 71% reduction of ,1 collagen type IV mRNA, and a 29% reduction of fibronectin mRNA. This study is the first to investigate decorin transfection into human mesangial cells, and supports the use of the decorin gene to control the progression of glomerular and interstitial fibrosis in kidney diseases. © 2002 Wiley-Liss, Inc. [source] Protective effect of Hachimi-jio-gan against renal failure in a subtotal nephrectomy rat modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2005Noriko Yamabe The protective effect of Hachimi-jio-gan extract against chronic renal failure in a subtotal nephrectomy rat model was investigated. The level of serum urea nitrogen by nephrectomy was increased over 15 weeks, but the administration of Hachimi-jio-gan at 50 and 200 mg led to the decrease. In addition, the levels of creatinine (Cr), urinary methylguanidine (MG) and MG/Cr were increased, whereas Cr clearance dramatically decreased in nephrectomized rats. However, oral administration of Hachimi-jio-gan extract prevented the elevation of these uremic toxins in serum and urine, and the production of hydroxyl radical. Moreover, nephrectomy led to a significant decline in superoxide dismutase (SOD) and catalase activities, but increased glutathione peroxidase activity compared with normal levels, indicating an abnormal antioxidative system. The increased activity of both SOD and catalase by the oral administration of Hachimi-jio-gan suggested that these enzymes are associated with the protective role of Hachimi-jio-gan extract against oxidative stress by nephrectomy. Moreover, the decrease in serum albumin in nephrectomized control rats was increased and proteinuria was ameliorated by the administration of Hachimi-jio-gan with improved glomerular hyalinosis, interstitial fibrosis and inflammation, suggesting the beneficial effect of Hachimi-jio-gan to prevent glomerular sclerosis and progressive renal fibrosis. This study suggests that Hachimi-jio-gan plays a protective role in the progression of chronic renal failure through the decline in uremic toxins, elevation of antioxidative enzyme activity such as SOD and catalase, and amelioration of histopathological lesions in the kidney. [source] R2: Identification of renal potential progenitor/stem cells that participate in the renal regeneration processes of kidney allograft fibrosisNEPHROLOGY, Issue 6 2008JI BAO SUMMARY: Aim: Many strategies are explored to ameliorate kidney allograft tubular atrophy and interstitial fibrosis (TA/IF), but little progress has been achieved. The latest evidence suggested that CD133+ cell in kidney represent a potential multipotent adult resident stem cell population that may contribute to the renal injury repair. Here we investigate whether the CD133+ cells exist in transplanted renal and exert a growth and self-repair procedure in TA/IF. Methods: Allografts from rat kidney transplant models were harvested at 4 weeks, 8 weeks and 12 weeks post transplantation. We performed immunohistochemistry to detect the CD133+ cells and immunofluorescence to detect the co-expression of CD133 or Pax-2 with Ki-67. We furthermore analysed the E-cadherin using serial sections. Results: CD133+ cells were seldom seen in control kidney, but distributed sporadically in the cortex parenchyma along with the deterioration of TA/IF. The number of CD133+ cell increased after 4 weeks and reached the peak at 8 weeks, then decreased at 12 weeks. From 8 weeks, some new tubules expressing E-cadherin were constructed with CD133+ cells. Almost all the CD133+ cells were Ki-67-positive, but not all the Ki-67+ cells expressed CD133. The rest Ki-67+ cells almost expressed Pax-2. Conclusion: Our study reveals that when majority of the tubules are damaged, a self-repair mechanism is evoked by potential adult stem cells to compensate the renal function. Thus, potential adult resident stem cells offer a new avenue for autologous cell therapies in TA/IF. [source] Significance of incidental mesangial IgA deposition in minimal change nephrotic syndromeNEPHROLOGY, Issue 2001M Tsukada Background: Incidental IgA deposition in glomerular mesangium exists in 10,20% of autopsy kidneys1,2 or renal allograft donors.3 In the present study, we examined the clinicopathological features of incidental mesangial IgA deposition in renal biopsy from patients with minimal change nephrotic syndrome (MCNS) to understand the significance of mesangial IgA deposition in MCNS and pathogenesis of IgA nephropathy. Patients and Methods: From January 1994 to September 2000, 63 patients were diagnosed with MCNS by renal biopsy at Kidney Center, Tokyo Women's Medical University. Mesangial IgA and C3 deposition was examined by immunofluorescence staining using frozen sections. The frequency of IgA and C3 deposition in MCNS and clinicopathological features of IgA-positive patients with MCNS were investigated. Results: The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%) (Fig. 1). The serum IgA concentration was significantly higher in the IgA-positive patients than in the IgA-negative patients (309 ± 75 mg/dL versus 245 ± 106 mg/dL, P = 0.043) (Fig. 2). The urinary red blood cell count was higher in IgA-positive patients than in IgA-negative patients, although not significantly different (11.7 ± 12.7 counts/HPF versus 5.3 ± 4.0 counts/HPF, P = 0.067) (Fig. 3). Other clinical parameters (age, sex, amount of proteinuria, serum creatinine and creatinine clearance) were not significantly different. Histologically, no significant differences were observed between IgA-positive and IgA-negative patients in following parameters: grade of mesangial cell proliferation and mesangial matrix increase, extents of tubular atrophy and interstitial fibrosis and grade of vascular sclerosis. After steroid treatment, all 15 patients with mesangial IgA deposition had become complete remission, although three patients once relapsed proteinuria. The haematuria also disappeared after steroid treatment in these patients. Figure 1. The frequency of mesangial IgA and C3 deposition in MCNS patients (n = 63). The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%). Figure 2. The serum IgA concentration of the MCNS patients with and without mesangial IgA deposition. The serum IgA concentration was significantly higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48) (309 ± 75 mg/dL vs 245 ± 106 mg/dL, P = 0.043). Figure 3. The urinary red blood cell counts of the MCNS patients with and without mesangial IgA deposition. The urinary red blood cell count was higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48), although not significantly different (11.7 ± 12.7 counts/HPF vs 5.3 ± 4.0 counts/HPF, P = 0.067). Conclusion: The incidental mesangial IgA deposition was frequently observed in MCNS patients (15/60 patients, 23.8%). The phenomenon of mesangial IgA deposition in MCNS patients was related to higher serum IgA concentration and might cause slight haematuria. However, no influence of mesangial IgA deposition was found on the renal function and the clinical outcome of MCNS after treatment. [source] Renal impairment in deoxycorticosterone acetate-salt hypertensive ratsNEPHROLOGY, Issue 4 2000Catherine Dallemagne Summary: This study has compared renal function in deoxycorticosterone (DOCA)-salt hypertensive Wistar rats (uninephrectomy followed by administration of DOCA 25 mg subcutaneously every fourth day and 1% NaCl in the drinking water) with various control rats using the isolated perfused kidney preparation. The systolic blood pressure of DOCA-salt hypertensive rats was 180 ± 10 mmHg (uninephrectomy controls: 136 ± 9 mmHg) while normalization of calcium intake (DOCA-Ca rats, 1% CaCl2 in water) attenuated this increase (systolic blood pressure, 146 ± 5 mmHg). Renal mass corrected for body weight increased by 25% after uninephrectomy, 55% in uninephrectomized rats given NaCl, 152% in DOCA-salt rats and 147% in DOCA-Ca rats. At a renal perfusion pressure of 135 mmHg, isolated perfused kidneys from DOCA-salt rats showed decreases of 48% in glomerular filtration rate and 69% in sodium excretion with an increase of 44% in renal vascular resistance compared with uninephrectomized rats. There were no significant differences in renal function between DOCA-salt and DOCA-Ca rats. Histological assessment of renal pathology showed proximal tubular hypertrophy and hyperplasia, marked focal distal tubular atrophy, interstitial fibrosis and glomerular hypercellularity in DOCA rats compared with UNX rats. Lesions were less obvious in UNX-salt or DOCA-Ca rats. The lack of direct correlation between alterations in function and pathology may be explained by the compensatory effect of remaining healthy or hypertrophied nephrons. Thus, the DOCA-salt model of hypertension in rats is associated with marked structural kidney damage and severely decreased kidney function. Marked attenuation of systemic hypertension by normalizing calcium intake in DOCA-salt rats did not prevent impairment of kidney function. [source] Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathyPATHOLOGY INTERNATIONAL, Issue 5-6 2002Diange Liu The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen-binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47-expressing cells were identified as ,-smooth muscle actin-positive myofibroblasts and vimentin-positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy. [source] Steroid avoidance using sirolimus and cyclosporine in pediatric renal transplantation: One year analysisPEDIATRIC TRANSPLANTATION, Issue 1 2010Franca M. Iorember Iorember FM, Patel HP, Ohana A, Hayes JR, Mahan JD, Baker PB, Rajab A. Steroid avoidance using sirolimus and cyclosporine in pediatric renal transplantation: One year analysis. Pediatr Transplantation 2010: 14: 93,99. © 2009 John Wiley & Sons A/S. Abstract:, Steroids are commonly used in pediatric renal transplantation, but have numerous adverse effects. This retrospective study compares one-yr outcomes in 22 pediatric renal transplant recipients receiving SRL and CSA as primary immunosuppression (steroid-avoidance group) to age- and gender-matched historical controls receiving CSA, MMF, and prednisone (steroid group). At one yr, both groups had similar graft survival, acute rejection, and estimated GFR. Subjects in the steroid-avoidance group had better linear growth, less excessive weight gain and were less likely to have an increase in antihypertensive medication use. Subjects in the steroid-avoidance group were more likely to be started on lipid lowering medications and erythropoiesis stimulating agents. Despite having a greater proportion of living donors, the steroid-avoidance group had a similar GFR compared to the steroid group at one month. The steroid-avoidance group was also more likely to have a biopsy for elevated Cr that was not because of rejection and had more interstitial fibrosis noted. We conclude that using a steroid-avoidance immunosuppression regimen of SRL and CSA results in comparable rejection rates and short-term graft function with less steroid-associated morbidity. However, early findings also suggest possible potentiation of CSA nephrotoxicity by SRL in some children. [source] Features of chronic allograft rejection on rat small intestine transplantationPEDIATRIC TRANSPLANTATION, Issue 2 2007Hao Ma Abstract:, The aim of this study was to develop a model of chronic rejection of the entire small intestine transplantation and to analyze the features of chronic rejection. Allogenic small bowel transplantation was performed in a rat combination of Lewis to F344. Intestines were procured at the 60th and the 90th day after operation. We compared the semiquantitative score of histological parameters. The immunological components involved in the chronic rejection process were evaluated by immunohistochemical staining and the cytokine levels in grafts. The significant characteristics of the allograft on histology were changes of villous architecture, interstitial fibrosis, leukocyte infiltration, and obliterative arteriopathy. Allografts on the 60th day post-transplantation had more score in inflammatory events, while the grafts on the 90th day after operation had more values in ischemia/fibrotic events. The number of infiltrating CD4, CD8 and macrophage cells in allografts progressively decreased over time. The level of intrgraft cytokines such as IL-6, TNF- , and IL-10 in the 90th day after transplantation also decreased compared with that in the 60th day. These data suggested that in the early stage (POD 60), there were more active and intense inflammatory events; later (POD 90) allografts manifested less inflammation and more arterial obliteration and fibrosis. [source] Dyspnea secondary to pulmonary hematopoiesis as presenting symptom of myelofibrosis with myeloid metaplasiaAMERICAN JOURNAL OF HEMATOLOGY, Issue 2 2006Elisa Rumi Abstract We report a case of a patient with myelofibrosis with myeloid metaplasia (MMM) who presented with progressive dyspnea of unexplained origin. Splenomegaly, blood smear, and bone marrow findings allowed diagnosis of MMM. High-resolution CT chest scan revealed diffuse septal thickening, while echocardiography and electrocardiogram showed no indirect evidence of pulmonary hypertension. Finally, lung biopsy revealed irregularly distributed interstitial fibrosis with islands of erythroblasts, immature granulocytic elements, and dysplastic megakaryocytes, allowing diagnosis of pulmonary extramedullary hematopoiesis (EMH). The patient received hydroxyurea as cytoreductive agent, obtaining a good hematologic response and an improvement of dyspnea. Note that, in this patient, dyspnea was the first clinical symptom of MMM; the dyspnea was not associated with pulmonary hypertension and improved following cytoreductive treatment. This case points to the importance of suspecting pulmonary EMH when unexplained progressive dyspnea occurs in a patient with MMM. Early recognition of pulmonary EMH may prevent PH and favor a better response to therapy. Am. J. Hematol. 81:124,127, 2006. © 2006 Wiley-Liss, Inc. [source] Interstitial pulmonary fibrosis after severe exposure to welding fumesAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 4 2002U. Buerke MD Abstract Background Interstitial pulmonary fibrosis (IPF) is reported after long term, severe exposure to welding fumes in poorly ventilated workplaces. Methods Fifteen welders with IPF were examined,13 in our outpatient clinic,from 1990 to 1997. Occupational histories and examinations, lung function analyses, symptoms and clinical findings, histological analyses in 13 patients partly including SEM/EDX-analyses, chest X-rays, chest computed tomographies were conducted. Results Duration of work as welders was 28 years and the cumulative dose of welding fumes 221 mg/m3,×,years (median). Lung function studies found pattern of restriction or combined restriction-obstruction, lower diffusion capacity, and reduced blood oxygen tension at exercise. Histologicallly, patchy interstitial fibrosis was noted. Accumulations of particulate matter typically for welding fume were detected. EDX showed increase of iron load and close topographical relationship to welding fume particles embedded in areas of scattered fibrosis. Conclusion While epidemiological data are limited, it is reasonable to conclude that a causal relationship exists between IPF in welders with long term exposure to high concentrations of welding fumes. Am. J. Ind. Med. 41:259,268, 2002. © 2002 Wiley-Liss, Inc. [source] Proteomic profiling of KATP channel-deficient hypertensive heart maps risk for maladaptive cardiomyopathic outcomePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2009Jelena Zlatkovic Abstract KCNJ11 null mutants, lacking Kir6.2 ATP-sensitive K+ (KATP) channels, exhibit a marked susceptibility towards hypertension (HTN)-induced heart failure. To gain insight into the molecular alterations induced by knockout of this metabolic sensor under hemodynamic stress, wild-type (WT) and Kir6.2 knockout (Kir6.2-KO) cardiac proteomes were profiled by comparative 2-DE and Orbitrap MS. Despite equivalent systemic HTN produced by chronic hyperaldosteronism, 114 unique proteins were altered in Kir6.2-KO compared to WT hearts. Bioinformatic analysis linked the primary biological function of the KATP channel-dependent protein cohort to energetic metabolism (64% of proteins), followed by signaling infrastructure (36%) including oxidoreductases, stress-related chaperones, processes supporting protein degradation, transcription and translation, and cytostructure. Mapped protein,protein relationships authenticated the primary impact on metabolic pathways, delineating the KATP channel-dependent subproteome within a nonstochastic network. Iterative systems interrogation of the proteomic web prioritized heart-specific adverse effects, i.e., "Cardiac Damage", "Cardiac Enlargement", and "Cardiac Fibrosis", exposing a predisposition for the development of cardiomyopathic traits in the hypertensive Kir6.2-KO. Validating this maladaptive forecast, phenotyping documented an aggravated myocardial contractile performance, a massive interstitial fibrosis and an exaggerated left ventricular size, all prognostic indices of poor outcome. Thus, Kir6.2 ablation engenders unfavorable proteomic remodeling in hypertensive hearts, providing a composite molecular substrate for pathologic stress-associated cardiovascular disease. [source] Clinicopathological features of chronic hypersensitivity pneumonitisRESPIROLOGY, Issue 4 2002HIROSHI HAYAKAWA Objective: Only limited information exists concerning the clinical and pathological features of chronic hypersensitivity pneumonitis (HP) in Japan and elsewhere. We present data on clinicopathological features of chronic HP obtained through a Japanese nationwide survey. Methodology: We studied the clinical and pathological findings in 10 patients with chronic HP who underwent surgical lung biopsy or postmortem examination. Results: There were three types of clinical course: six of the 10 patients had persistent symptoms followed by repeated acute episodes; two showed a subacute onset with persistent symptoms; and two exhibited an insidious onset. Five patients made no attempt to avoid antigen exposure and they all had progressive disease. Pathological findings indicated that lesions were mainly centrilobular with or without epithelioid cell granulomas in specimens obtained during the acute or subacute stage. In contrast, most patients in the chronic stage predominantly showed interstitial fibrosis with a usual interstitial pneumonia pattern. Conclusions: The pathological findings of chronic HP depend on the stage of the disease at tissue sampling. [source] Glomerular and tubular induction of the transcription factor c-Jun in human renal disease,THE JOURNAL OF PATHOLOGY, Issue 2 2007MH De Borst Abstract The transcription factor c-Jun regulates the expression of genes involved in proliferation and inflammation in many cell types but its role in human renal disease is largely unclear. In the current study we investigated whether c-Jun activation is associated with human renal disease and if c-Jun activation regulates pro-inflammatory and pro-fibrotic genes in renal cells. Activation of c-Jun was quantified by scoring renal expression of phosphorylated c-Jun (pc-Jun) in control human renal tissue and in biopsies from patients with various renal diseases (diabetic nephropathy, focal glomerulosclerosis, hypertension, IgA nephropathy, membranous glomerulopathy, minimal change disease, membranoproliferative glomerulonephritis, systemic lupus erythematosus, acute rejection, and Wegener's granulomatosis); this was correlated with parameters of renal damage. Furthermore, we studied the functional role of c-Jun activation in human tubular epithelial cells (HK-2) stimulated with TGF-,. Activated c-Jun was present in nuclei of glomerular and tubular cells in all human renal diseases, but only sporadically in controls. Across the diseases, the extent of pc-Jun expression correlated with the degree of focal glomerulosclerosis, interstitial fibrosis, cell proliferation, kidney injury molecule-1 (Kim-1) expression, macrophage accumulation, and impairment of renal function. In HK-2 cells, TGF-, induced c-Jun activation after 1 h (+40%, p < 0.001) and 24 h (+160%, p < 0.001). The specific c-Jun N-terminal kinase (JNK) inhibitor SP600125 abolished c-Jun phosphorylation at all time points and blunted TGF-,- or BSA-induced procollagen-1, 1 and MCP-1 gene expression in HK-2 cells. We conclude that in human renal disease, the transcription factor c-Jun is activated in glomerular and tubular cells. Activation of c-Jun may be involved in the regulation of inflammation and/or fibrosis in human renal disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Effects of ACE Inhibition and Beta-Blockade on Female Genital Structures in Spontaneously Hypertensive RatsTHE JOURNAL OF SEXUAL MEDICINE, Issue 6 2007Jorge E. Toblli MD ABSTRACT Introduction and Aim., This study evaluated the possible differences between an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker concerning their potential protective role on female external genitalia in spontaneously hypertensive rats (SHR). Main Outcome Measures., Morphological changes in the clitoris after antihypertensive treatments. Methods., For 6 months, SHR received no treatment; SHR + ramipril (RAM), SHR + atenolol (AT), and control Wistar Kyoto (WKY) rats received no treatment. Clitorises were processed for immunohistochemistry using anti-,-smooth muscle actin (,-SMA), anti-collagen I and III, anti-transforming growth factor ,1 (TGF,1), and anti-endothelial nitric oxide synthase (eNOS) antibodies. Results., SHR + RAM and SHR + AT presented significantly lower blood pressure in both groups vs. untreated SHR. Compared with WKY, ,-SMA was increased in the arteries and in the cavernous spaces of the clitoris together with a marked increase in wall/lumen ratio in clitoral vessels in untreated SHR. All these alterations were diminished in SHR + AT (P < 0.01). SHR + RAM presented differences with respect to SHR + AT in the reduction of these variables. TGF,1 expression in the vessel wall from the clitoris and collagen I and III deposition in the interstitium from the clitoris in untreated SHR were significantly more (P < 0.01) than in WKY. While SHR + AT showed a mild decrease in these variables, SHR + RAM presented a significant reduction (P < 0.01) in TGF,1 expression interstitial fibrosis and in both types of collagens. Positive immunostaining of eNOS in the sinusoidal endothelium from the clitoris was less (P < 0.01) in untreated SHR (3.4 ± 1.3%) and SHR + AT (5.1 ± 1.2%) than in SHR + RAM (17.2 ± 1.6%) and WKY (15.9 ± 1.7%). Untreated SHR and SHR + AT presented more surrounding connective tissue at the perineurium in the clitoris (P < 0.01) than SHR + RAM. Conclusion., ACE inhibition provided a considerable protective role on the female external genitalia structures in SHR by a mechanism that may be, at least in part, independent of the degree of blood pressure lowering. Toblli JE, Cao G, Casabé AR, and Bechara AJ. Effects of ACE inhibition and beta-blockade on female genital structures in spontaneously hypertensive rats. J Sex Med 2007;4:1593,1603. [source] Inflammation in Areas of Tubular Atrophy in Kidney Allograft Biopsies: A Potent Predictor of Allograft FailureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010R. B. Mannon The Banff scoring schema provides a common ground to analyze kidney transplant biopsies. Interstitial inflammation (i) and tubulitis (t) in areas of viable tissue are features in scoring acute rejection, but are excluded in areas of tubular atrophy (TA). We studied inflammation and tubulitis in a cohort of kidney transplant recipients undergoing allograft biopsy for new-onset late graft dysfunction (N = 337). We found inflammation (,iatr') and tubulitis (,tatr') in regions of fibrosis and atrophy to be strongly correlated with each other (p < 0.0001). Moreover, iatr was strongly associated with death-censored graft failure when compared to recipients whose biopsies had no inflammation, even after adjusting for the presence of interstitial fibrosis (Hazard Ratio = 2.31, [1.10,4.83]; p = 0.0262) or TA (hazard ratio = 2.42, [1.16,5.08]; p = 0.191), serum creatinine at the time of biopsy, time to biopsy and i score. Further, these results did not qualitatively change after additional adjustments for C4d staining or donor specific antibody. Stepwise regression identified the most significant markers of graft failure which include iatr score. We propose that a more global assessment of inflammation in kidney allograft biopsies to include inflammation in atrophic areas may provide better prognostic information. Phenotypic characterization of these inflammatory cells and appropriate treatment may ameliorate late allograft failure. [source] | ||||||||||||||||||||||||||||||||||