Connective Tissue Growth Factor ; Humans ; Myocardial Infarction ; physiopathology ; Ventricular Remodeling

OBJECTIVETo explore the role of expression of connective tissue growth factor (CTGF) in pulmonary vascular remodeling of pulmonary hypertensive rats, and investigate the regulation of CTGF expression by simvastatin in this animal model.

METHODSEighty male Sprague-Dawley rats (350 to 400 g) were randomized to 7 groups. The rats in group PM(1 - 21) (n = 10) and PM(1 - 35) (n = 12) were treated with pneumonectomy + monocrotaline (MCT), and sacrificed at the 21st or 35th experimental day;those in groups PMS(1 - 35) (n = 12), PMS(21 - 35) (n = 12), PMV(1 - 35) (n = 12) and PMV(21 - 35) (n = 12) were given daily lavage of simvastatin (or vehicle) as intervention measure which began from the 1st and 21st experimental days, respectively; additional 10 rats were used as control without any intervention. The animals were sacrificed at the end of experiment (35 th day) as hemodynamic measurements and study on the morphological parameters relevant to pulmonary vascular remodeling were performed on each group of rats. The expression of ET-1 mRNA, CTGF mRNA and protein, and synthesis of collagen in these pneumonectomized, MCT-treated rats were compared between control and rats treated with simvastatin.

RESULTSRats in PM(1 - 35) Group developed severe PAH (mPAP = 39.75 +/- 3.62 mm Hg) (1 mm Hg = 0.133 kPa), right ventricular hypertrophy [RV/(LV + S) ratio = 0.627 +/- 0.040], and arterial medial hypertrophy (WT% = 61.73 +/- 5.39), these parameters of the control animals were 17.10 +/- 1.20 mm Hg, 0.262 +/- 0.018 and 14.71 +/- 1.16, respectively. CTGF mRNA and protein were mainly located in pulmonary arterial smooth muscle cells and interstitial macrophage shown by in situ hybridization and immunohistochemistry, respectively. The expression of ET-1 mRNA and CTGF mRNA detected by fluorescent quantitative RT-PCR in Group PM(1 - 35) were significantly increased in comparison with controls, and so did the CTGF protein expression determined by Western blotting in these diseased rats. The content of hydroxyproline (1.30 +/- 0.19 microg/mg wet lung) was remarkably higher than that of control animals (0.56 +/- 0.10 microg/mg wet lung). The up-regulation of ET-1 and CTGF gene expression, and elevated synthesis of hydroxyproline were reversed in rats intervened with simvastatin. The pulmonary hypertension, right ventricular hypertrophy and medial hypertrophy were attenuated in all simvastatin-treated rats no matter the intervention was initiated from the beginning or midway of the study.

CONCLUSIONThe up-regulation of CTGF gene expression may play an important role in the development of pulmonary vascular remodeling in PAH. Simvastatin can prevent and, to some extent, reverse the vascular remodeling via down-regulation of CTGF gene expression.

Animals ; Connective Tissue Growth Factor ; metabolism ; Down-Regulation ; Hypertension, Pulmonary ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley ; Simvastatin ; pharmacology

OBJECTIVETo investigate the prevalence of anti-endothelial cell antibodies (AECAs) in the sera of connective tissue diseases (CTD) patients with pulmonary arterial hypertension (PAH) and its correlation with clinical manifestations.

METHODSAECAs in sera of 39 CTD patients with PAH, 22 CTD patients without PAH, and 10 healthy donors as controls were detected with Western blotting. The prevalence of different AECAs in different groups was compared and its correlation with clinical manifestations was also investigated.

RESULTSThe prevalence of AECAs was 82.1% in CTD patients with PAH, 72.7% in CTD patients without PAH, and 20.0% in healthy donors. Anti-22 kD AECA was only detected in CTD patients with PAH (15.4%). Anti-75 kD AECA was more frequently detected in CTD patients with PAH than in those without PAH (51.3% vs. 22.7%, P < 0.05). In CTD patients with PAH, anti-75 kD AECA was more frequently detected in those with Raynaud's phenomenon or with positive anti-RNP antibody.

CONCLUSIONAECAs could be frequently detected in CTD patients with or without PAH, while anti-22 kD and anti-75 kD AECA might be specific in CTD patients with PAH.

Adult ; Autoantibodies ; blood ; immunology ; Cell Line ; Connective Tissue Diseases ; blood ; immunology ; pathology ; physiopathology ; Endothelial Cells ; cytology ; immunology ; Female ; Humans ; Hypertension, Pulmonary ; blood ; immunology ; pathology ; physiopathology ; Middle Aged

PURPOSE: Tibial plateau fracture (TPF) is a devastating injury as it shatters lower articular surface of the largest joint. Apart from bony injury, TPF can lead to great soft tissue envelope compromise which affects the treatment plan and outcome. In the present study, clinical results were assessed in cases of high energy TPFs treated in staged manner. METHODS: Twenty-three (20 males and 3 females) patients of high energy communited TPFs (Schatzker type V and VI) were consecutively treated. All the patient had compromise of overlying skin conditions. They were all successively scheduled for staged treatment plan which comprised of application of bridging knee external fixator on the first day of admission and definitive internal fixation after skin and soft tissue overlying the fracture were healed. Schatzker type I, II, III and IV were excluded from the study. Primary survey was done and patient who had head injury, chest and abdominal injury, pelvic injury and contralateral limb injury and open fractures were excluded from the study. The patients were also evaluated in terms of wound complications, axial and rotary alignment of limb, fixation failure, articular congruity and range of motion of the knees and post injury employment. Statistical analysis was done using SPSS software. RESULTS: Maximum follow-up period was 13 months. All the fractures were united at final follow-up. Clinical evaluation was done with the Tegner Lysholm knee scoring scale. Excellent results were found in 78% cases and good and fair results in 22% cases. There was significant correlation between range of motion and the Tegner Lysholm knee score (p < 0.001, Pearson correlation coefficient = 0.741). The correlation between the score and the radiographical union duration was significant (p = 0.006, Pearson correlation coefficient = -0.554). CONCLUSION A staged treatment plan allows healing of soft tissue envelope, with avoidance of dreadful complications such as compartment syndrome and chronic infection. In addition, a staged treatment strategy does not hamper the fracture reduction, bony union and the functional results.
Adult ; Compartment Syndromes ; prevention & control ; Connective Tissue ; physiopathology ; Female ; Fracture Fixation, Internal ; methods ; Fracture Healing ; Fractures, Comminuted ; physiopathology ; surgery ; Humans ; Knee ; physiopathology ; Male ; Middle Aged ; Range of Motion, Articular ; Tibial Fractures ; physiopathology ; surgery ; Treatment Outcome

OBJECTIVETo study the epidemiology, clinical characteristics and prognosis of children with pulmonary arterial hypertension (PAH) secondary to connective tissue disease (CTD).

METHODSThe clinical record files of the pediatric inpatient with PAH in the population of CTD in the hospital treated between January 2000 and January 2007 were analyzed retrospectively.

RESULTS(1) In 299 patients with CTD and complete Doppler echocardiography files, 31 (31/299, 10.4%) patients (28 females and 3 males), aged from 7 to 18 years (average: 12.5 years), were found to have PAH, in whom, 5(62.5%)in 8 patients with overlapped CTD (OCTD), 2 (50.0%) in 4 patients with antiphospholipid syndrome (APS), 4(28.6%) in 14 patients with systematic vasculitis (SV), 3 (10.7%) in 28 patients with dermatomyositis (DM), 17(7.6%) in 223 systemic lupus erythematosus (SLE) had PAH. The CTD-associated PAH occurred in the 3rd week to 5th year after initial CTD manifestations (median onset: 1.5 years). (2) The onset of CTD-associated PAH was obscure and children with severe CTD-associated PAH presented with dyspnea (18/31, 58.1%) and heart failure (9/31, 29.0%). The children with Raynaud's phenomenon or positive anticardiophospholipid antibody (ACL) or positive lupus anticoagulant (LA) were prone to have more severe PAH. (3) Doppler echocardiography and pulmonary function test, especially the test of pulmonary diffusion function of CO (D(LCO)) were necessary to detect PAH early. (4) After treatment, the pulmonary arterial pressure in mild and moderate PAH cases could be normalized and in severe PAH cases could be decreased to mild or moderate levels. There was a lower PaO(2) level (P < 0.01), a higher pulmonary arterial systolic pressure (PASP) level (P < 0.05) in the cases of CTD-PAH who died as compared with the live patients.

CONCLUSIONSPAH is a common complication of CTDs, which occurs often 1.5 years after initial CTD manifestations. The early associated symptom is obscure and the severe cases manifest with dyspnea and heart failure. Those with Raynaud's phenomenon and positive ACL and LA are prone to develop more severe PAH. Early and regular Doppler echocardiography and pulmonary function test are necessary to detect PAH early. Severe CTD associated PAH in children could lead to poor outcome. PASP classification and PaO(2) level are important factors affecting prognosis.

Adolescent ; Child ; Connective Tissue Diseases ; complications ; diagnostic imaging ; physiopathology ; Echocardiography, Doppler ; Female ; Humans ; Hypertension, Pulmonary ; diagnostic imaging ; etiology ; Male ; Prognosis ; Respiratory Function Tests ; Retrospective Studies

PURPOSE: To evaluate long-term visual outcome of arteriovenous adventitial sheathotomy in BRVO-induced macular edema. METHODS: The visual outcomes of 8 patients following vitrectomy with arteriovenous adventitial sheathotomy for BVO-induced macular edema (surgery group) were retrospectively evaluated. The three-year post-operative visual acuity of the surgery group was compared with that of the conservatively managed controls. RESULTS: All patients were followed for a minimum of 36 months. Mean BCVA (logMAR) in the surgery group changed from 1.10+/-0.34 to 1.19+/-0.70 and to 0.80+/-0.36 at 12 and 36 months, respectively (p=0.959 at 12 months, p=0.018 at 36 months). In the control group, visual acuity improved from 1.15+/-0.43 to 0.43+/-0.44 and to 0.43+/-0.39 at 12 and 36 months, respectively (p=0.015 at 12 months, at p=0.003 at 36 months). A strong trend toward better visual acuity at 12 months and final examination was observed for controls. (surgery vs. control group, p=0.052 at 12 months, p=0.066 at 36 months). CONCLUSIONS: Considering the favorable natural course of BVO and the unproven effect of reperfusion on macular edema, surgical efficacy of arteriovenous adventitial sheathotomy requires further evaluation.
Aged ; Connective Tissue/*surgery ; Decompression, Surgical/methods ; Female ; Humans ; Macular Edema/etiology/physiopathology/*surgery ; Male ; Middle Aged ; Retinal Artery ; Retinal Vein ; Retinal Vein Occlusion/complications/physiopathology/*surgery ; Retrospective Studies ; Treatment Outcome ; Visual Acuity/*physiology ; Vitrectomy/*methods

BACKGROUNDInvolvement of peripheral nerves in dermatomyositis (DM) and polymyositis (PM) is less well known. In the present study we retrospectively analyzed the clinical and electrophysiological records of hospital inpatients with a diagnosis of DM or PM to investigate the association of DM/PM and peripheral neuropathy.

METHODSThe data of inpatients diagnosed with DM or PM were collected in Peking Union Medical College Hospital, and 186 patients (118 patients with DM and 68 with PM) were retrospectively analyzed. Nerve conduction studies (NCSs) of the median nerve, ulnar nerve, posterior tibial nerve, and common peroneal nerve were examined simultaneously.

RESULTSThere were 71 (38.2%) patients with abnormal NCS findings, 37 (19.9%) with pure motor involvement (decreased compound muscle action potential, CMAP), and 34 (18.3%) with peripheral neuropathy. Of the 34 peripheral neuropathy patients, 14 (7.5%) had polyneuropathy, 1 (0.5%) had multiple mononeuropathy, 16 (8.6%) had carpal tunnel syndrome (CTS), 1 (0.5%) had trigeminal sensory neuropathy, 1 (0.5%) had ulnar sensory neuropathy, and 1 (0.5%) had brachial plexus involvement. The prevalence of malignant disease (3/34, 8.8%), other connective tissue diseases (CTDs) (7/34, 20.6%) and diabetes (6/34, 17.6%) was significantly greater in DM/PM patients with peripheral neuropathy (chi(2) = 15.855, P = 0.000) compared with DM/PM patients without involvement of peripheral nerves (5/115, 4.3% and 7/115, 6.1%, respectively).

CONCLUSIONSPeripheral neuropathy in DM/PM often suggests a complication with cancer, other CTDs, diabetes or CTS. From a practical point of view, NCS for DM/PM may help find the underlying disorders.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Connective Tissue Diseases ; complications ; Dermatomyositis ; complications ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Neural Conduction ; Peripheral Nervous System Diseases ; etiology ; Polymyositis ; complications ; physiopathology ; Retrospective Studies

OBJECTIVETo explore the effects of rosiglitazone (RSG), an agonist of peroxisome proliferators-activated receptor-gamma (PPAR-gamma), on the up-regulation of connective tissue growth factor (CTGF) and the deposition of type I and type III collagens in the pulmonary arteries of rats suffering from fibrosis in lung.

METHODSForty-eight male Sprague-Dawley rats were randomly divided into 4 groups: bleomycin (BLM) plus normal saline (NS) group (n=21), BLM plus RSG group (n=9), NS plus NS group (n=9), and NS plus RSG group (n=9). The rats were received single intratracheal instillation of BLM (5 mg/kg bw) or equal volume of NS as control, and received intra-gastric adminnistration of RSG (3 mg/(kg x day), 14 day) or the same volume of NS as vehicle. In vio, the observation was conducted on day 14 after intratracheal instillation. In vitro, the pulmonary arteries of rats on day 14 after BLM were isolated and incubated with DMEM alone or with RSG (37 degrees C, 5% CO2, for 24 h.

RESULTSIn vivo, the expression and the content of CTGF, the contents of type I and type III collagens, and the ratio of type I collagen and type III collagen were increased in the pulmonary arteries of BLM-instilled rats, compared with those of NS-instilled rats (All P < 0.05). The above abnormal changes were ameliorated by RSG (All P < 0.05). In vitro, RSG blocked the up-regulation of CTGF (P < 0.05), but not the deposition of type I collagen and type III collagen in the pulmonary arteries isolated from the BLM-instilled rats (P > 0.05).

CONCLUSIONThe results suggest that RSG directly blocks the up-regulation of CTGF in pulmonary arteries of rats suffering from fibrosis in lung, and this might be one of the mechanisms underling the ameliorated pulmonary arterial remodeling by RSG.

Animals ; Bleomycin ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Connective Tissue Growth Factor ; metabolism ; Down-Regulation ; drug effects ; Lung ; pathology ; Male ; PPAR gamma ; agonists ; Pulmonary Artery ; metabolism ; Pulmonary Fibrosis ; chemically induced ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Thiazolidinediones ; pharmacology

To summarized the experiences from our basic experimental and clinical research on peritoneal dialysis. In the past 16 years, peritoneal fibrosis rat models and rabbit models of peritonitis were first established successfully in our laboratory in China. Peritoneal mesothelial cells were also separated and identificated. Besides, we assessed the biocompatibility of peritoneal dialysis fluid and analyzed the molecular mechanism of peritoneal mesothelial cell injury. We demonstrated the key role of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and peroxisome proliferative activated receptor-gamma (PPAR-gamma) in the pathogenesis of peritoneal fibrosis, as well as their regulation of molecular mechanism. Furthermore, we transfected the plasmids encoding TGF-beta1-shRNA or pCTGF-shRNA into peritoneal cells and tissues by nanocarrier technologies. In clinical research, the positioning of peritoneal dialysis catheters, peritoneal dialysis treatment modalities and the prevention and treatment of its complications were studied. The characteristics and mechanism of solute transport in peritoneal dialysis was also explored.
Animals ; Connective Tissue Growth Factor ; metabolism ; Fibrosis ; physiopathology ; prevention & control ; Humans ; Kidney Failure, Chronic ; metabolism ; therapy ; Peritoneal Dialysis ; methods ; Peritoneal Dialysis, Continuous Ambulatory ; adverse effects ; Peritoneum ; pathology ; Rabbits ; Rats ; Retrospective Studies ; Tissue Adhesions ; physiopathology ; prevention & control ; Transforming Growth Factor beta ; metabolism

OBJECTIVESVentricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF.

METHODSThe animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction.

RESULTSCompared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P < 0.01), but ejection fraction (EF) and fractional shortening (FS) were decreased (P < 0.01). CTGF positive cells and expression of CTGF mRNA (0.609 +/- 0.065 vs 0.117 +/- 0.011, P < 0.01) were increased in HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were all decreased (P < 0.01), but FS and EF were increased (P < 0.01) in cases of HF treated with benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P < 0.01), EF and FS were lower (P < 0.01), CTGF positive cells and expression of CTGF mRNA were higher (P < 0.01) in HF group treated with benazepril than those of sham-operated group.

CONCLUSIONThe expression of CTGF was increased in the cardiomyocyte of young rats with HF and benazepril could prevent left ventricular from remodeling partly and improve cardiac function by inhibiting the expression of CTGF in cardiomyocyte in cases of HF.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Benzazepines ; pharmacology ; Connective Tissue Growth Factor ; metabolism ; Disease Models, Animal ; Heart Failure ; diagnostic imaging ; drug therapy ; metabolism ; physiopathology ; Immunohistochemistry ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; RNA, Messenger ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Ultrasonography ; Ventricular Dysfunction, Left ; diagnostic imaging ; drug therapy ; physiopathology ; Ventricular Remodeling ; drug effects