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In a previous study, we have demonstrated that overexpression of the tissue inhibitors of metalloproteinases-4 (TIMP-4) can inhibit the neointima formation in the rat carotid model. To define the functions of tissue inhibitor of metalloproteinases-4 (TIMP-4) in SMCs, we transduced human TIMP-4 cDNA into rat aortic SMCs by using adenoviral vector. Overexpression of TIMP-4 blocked the conversion of pro-MMP-2 to the active form and inhibited basic fibroblast growth factor-induced migration by 56.7% (p < 0.01). Overexpression of TIMP-4 markedly increased apoptotic cell death without changing their proliferation. Importantly, overexpression of human TIMP-4 in the wall of balloon-injured rat carotid artery also increased SMC apoptosis. The percentages of TUNEL-positive cells of total cells increased significantly in AdTIMP-4 infected group compared with AdGFP infected group. These findings demonstrate that TIMP-4 can inhibit SMCs migration and induce apoptosis in vitro and in vivo, which may generate new targets for prevention and treatment of vascular diseases.

This is a prospective study of transcatheter implantation of 11 intravascular stents in 7 patients with status/post (S/P) surgical correction of major cardiovascular lesions. The safety and efficacy of balloon-expandable stents for treatment of peripheral pulmonary artery stenosis (PPAS) is evaluated and analyzed. Although the transcatheter implantation of intravascular stents has been reported as a possible treatment for stenotic peripheral pulmonary arteries, the results of intermediate follow-up studies on patients with S/P surgical correction for residual PPAS need to be evaluated. From June 1998 to December 2001, a total of 15 patients with PPAS having S/P surgery for major cardiovascular lesions were enrolled in this study. Eight of them had redo surgery after complete evaluation and the other 7 patients who might be at higher risk of mortality or morbidity from redo surgery, underwent transcatheter implantation of stents to dilate significant PPAS. Tetralogy of Fallot, S/P total correction, was done in 6 and transposition of great vessels, S/P Jatene operation, was done in 1. There were 10 stents (P 308 Palmaz stent x8 and Intrastent x2) implantation for 10 sites of the stenotic PPAS in these 7 patients, who were aged from 3.6 to 17.3 (10.1 +/- 5.6) years and had body weights ranging from 17 to 72.5 (37.1 +/- 23.0) kg. The narrowest diameter of the stenotic peripheral pulmonary arteries and pressure gradients across the stenosis were measured before and after implantation of stents. A follow-up catheterization and pulmonary angiography was performed 1 year later to evaluate the intermediate efficacy of stents implantation. All the stenotic peripheral pulmonary arteries of these 7 patients had a significant reduction of pressure gradients immediately after the procedure. The narrowest mean diameter of pulmonary arteries increased from 6.7 +/- 3.4 to 11.3 +/- 3.0 mm (p < 0.001), and the mean pressure gradient dropped from 31 +/- 9.9 to 11.4 +/- 4.6 mm Hg (p < 0.001). The follow-up catheterization 1 year later revealed a persistent effect in all but 1 patient. Only a young male presented with a recurrent stenosis with a pressure gradient of > or = 20 mm Hg, which was relieved by redilation with implantation of another stent. There was no immediate or intermediate complication. Transcatheter stent implantation for treatment of a significant residual PPAS after surgical correction of complicated congenital heart disease is a safe and effective procedure. Since children are growing with age, a long-term follow-up study to evaluate the effects and possible problems of stent implantation is mandatory.

Background: Total anomalous pulmonary venous return (TAPVR) is an uncommon congenital cardiovascular anomaly with poor natural prognosis. It has been detected more frequently in recent year due to the advent of echocardiography and cardiovascular magnetic resonance imaging (MRI). The aim of this study was to evaluate the clinical manifestations and outcomes in TAPVR patients with or without pulmonary venous obstruction (PVO)., Methods: From January 1985 to December 2002, a total of 27 cases with TAPVR at our institution were reviewed. Accurding to the preseace or assence of PVO, patients were divided into PVO group and non-PVO group. Patients' sex, age at diagnosis, types of TAPVR, clinical manifestations, surgical treatment and outcomes were evaluated., Results: All of them had received 2-dimensional (2-D) and color Doppler echocardiography examination. Cardiac catheterization was performed in all but 1 patient who died at the first day of birth. In addition, 10 of 27 cases had cardiovascular MRI for further study. The number of cases in PVO group and non-PVO group were 15 (56%) and 12 (44%), respectively. There was no significant difference in sex or pulmonary venous drainage sites between both groups. Cyanosis was more prevalent in the PVO group (80% vs. 30%, p = 0.038). Four (27%) cases PVO group and 3 (25%) cases of the non-PVO group had of the non-isolated cardiac lesions. Pulmonary hypertension was present in 18 (69%) of 26 cases who had received cardiac catheterization. Among them, 10 had PVO and 5 had systemic level of pulmonary arterial pressure. Seven (30%) of 23 patients who had received operation died; in contrast, 3 of 4 patients without operation expired. The remaining 1 did not had surgery because of complex heart disease. There was no significant difference in surgical mortality between PVO and non-PVO groups (33% vs. 27%)., Conclusions: Cyanosis is an obvious clinical symptom of obstructed TAPVR. Surgical mortality made no significant difference between obstructed and non-obstructed groups. Early detection and surgical treatment for TAPVR are important. Although cardiac catheterization and angiocardiography is the golden standard for the diagnosis, 2-D and color Doppler echocardiography can also provide quick and accurate diagnostic images of TAPVR.

Objective: To investigate the effect of rat hyperplasia suppressor gene-1(rHSG-1) on the proliferation of aortic vascular smooth muscle cells(VSMCs) from spontaneously hypertensive rats(SHR)., Methods: VSMCs were transfected with an adenoviral vector expressing rHSG-1(Ad5rHSG-1). The effect of rHSG-1 on the proliferation of VSMCs was investigated by cell counting, MTT assay and (3)H-thymidine incorporation. We also analyzed the cell-cycle using flow cytometry and detected the expression of p27(Kip1) and p21(Cip1) by Western Blot., Results: The proliferation of VSMCs infected with Ad5rHSG-1 was inhibited a 40% reduction compared with the control group(P<0.01). The cell cycle was arrested in G(0)/G(1) phase and the expression of p27(Kip1) and p21(Cip1) was upregulated after the VSMCs transfection with Ad5rHSG-1., Conclusion: Adenovirus-mediated gene transfer of rHSG-1 inhibits the cell cycle progression and thus the proliferation of VSMCs from SHR.

Objective: To investigate the effects of topical application of small dose of insulin on the wound healing of the scalded rats, so as to explore its mechanism., Methods: The rats employed in the study were subjected to deep partial thickness burn and were divided into group A (with subcutaneous injection of isotonic saline into the rat wounds as control), B and C (with subcutaneous injection of 0.1 U and 1 U insulin in the rat wounds respectively) and D (with subcutaneous injection of 0.1 U insulin in the rat abdomen as control). The wound healing time and wound healing rate were assessed every other day after 3 postburn days (PBDs). The histological changes of the wounds after injection were examined, the changes in the cell cycle of epidermal cells in the wound were analyzed by flow-cytometry, and blood glucose concentration of each group was determined., Results: The wound healing time in group B (18.36 +/- 4.12 d) was significantly shorter than that in other groups (A: 24.57 +/- 5.19 d, C: 21.46 +/- 2.97 d, D: 24.50 +/- 1.05 d, P < 0.01). The wound healing rate of the rats in group B in 5, 9, 11, 13, 15, 17 and 19 PBD was obviously higher than that in group A, and was markedly higher than that in group C on 17 PBD (P < 0.05 - 0.01). The epithelial layer was thinner with less epidermal nails but much more fibroblasts in epidermal layer in group A, while the epithelial layer was thicker with abundant epidermal nails in group B and C with many fibroblasts in the dermis. The amount of cells in S phase at 4 PBD in group B was dramatically higher than that in group A, and cells in G2M phase at 4 - 5 PBD in group B was also higher than that in group A and C (P < 0.05 - 0.01). The blood level of glucose in group A and B fluctuated between 3.42 to 4.62 mmol/L at 24 PBH, while that in group C and D decreased obviously 1 hour after injection (P < 0.01), but gradually returned to normal 4 hours after injection., Conclusion: Local injection of small dose of insulin may accelerate burn wound healing due to its role in promoting the proliferation and division of the repairing cells.

Recent genetic investigations have established that RhoB gain-of-function is sufficient to mediate the antitransforming effects of farnesyltransferase inhibitors (FTIs) in H-Ras-transformed fibroblast systems. In this study, we addressed the breadth and mechanism of RhoB action in epithelial cells transformed by oncoproteins which are themselves insensitive to FTI inactivation. Rat intestinal epithelial (RIE) cells transformed by activated K-Ras or Rac1 were highly sensitive to FTI-induced actin reorganization and growth inhibition, despite the inability of FTI to block prenylation of either K-Ras or Rac1. Ectopic expression of the geranylgeranylated RhoB isoform elicited in cells by FTI treatment phenocopied these effects. Analysis of RhoB effector domain mutants pointed to a role for PRK, a Rho effector kinase implicated in the physiological function of RhoB in intracellular receptor trafficking, and these findings were supported further by experiments in a fibroblast system. We propose that FTIs recruit the antioncogenic RhoB protein in the guise of RhoB-GG to interfere with signaling by pro-oncogenic Rho proteins, possibly by sequestering common exchange factors or effectors such as PRK that are important for cell transformation.

Objective: To optimize the systemic antibiotics in the treatment of the invasive infection of burns based on the successive monitoring of bacterial species harvested from the burn wound and subeschar tissues and their resistance to antibiotics., Methods: The data of bacteriological monitoring of burn wound and subeschar tissues in our burn center from 1995 to 2000 were retrospectively analyzed, and the characteristics of distribution and resistance to antibiotics of 1 109 strains from the wound in 612 patients and subeschar tissues in 146 patients were compared statistically by dividing them into two periods, i.e. from 1995 to 1997 and 1998 to 2000, respectively., Results: The percentage of Gram negative bacilli in identified strains was significantly higher than that of Gram positive cocci, and the majority of them were Pseudomonas and Enterobacteriaceae; Staphylococcus aureus comprised the majority of Gram positive cocci from 1998 to 2000, compared with the data collected in the period of from 1995 to 1997. The resistance of the Gram negative bacilli to Cephalosporins and Amikacin was increasing while the resistance of Pseudomonas to Netilmicin was decreasing from 18.52% of the tested strains down to 5.83%, and the resistance of Enterobacteriaceae to it was increasing from 18.75% to 55.79%. In addition, the resistance of Staphylococcus aureus to Netilmicin was down from 28.13% to 4.70%. Enterobacteriaceae were still sensitive to Imipenem, while the resistance of Pseudomonas to it became higher than that in the period from 1995 to 1997., Conclusion: The percentage of Gram negative bacilli in identified strains is significantly higher than that of Gram positive cocci and the pattern of their resistance to the antibiotics is changed meanwhile. Therefore, the choice of antibiotics for initial treatment of invasive infection in severe burns is a combination of Netilmicin and Imipenem, and, if Gram positive cocci is highly suspected, the first choice is Vancomycin.

Infective endocarditis remains a serious and complex disease with significant morbidity and mortality. Sixty cases of infective endocarditis were retrospectively reviewed, consisting of 41 males and 19 females aged 7 to 50 years (mean, 30 years). Congenital heart disease was diagnosed in 19 of the patients and rheumatic heart disease in 41. Congestive heart failure occurred in 36 and systemic embolism in 8 cases. Blood cultures were positive in only 21.7% of the cases, while vegetations were detected by 2-dimensional echocardiography in 70%. Elective surgery was performed in 57 patients and emergent operation for systemic arterial embolization and/or intractable congestive heart failure in 3 patients. Two patients required reoperation for postoperative bleeding. All but 2 patients had been followed up for 6 to 160 months with no evidence of reinfection. Three patients with mechanical valve implantation later died of intracranial bleeding due to over-anticoagulation. The remaining 55 resumed normal activity. The encouraging outcomes were the result of an aggressive diagnostic approach and early surgical intervention.

A method has been developed for the determination of triclosan in antibacterial detergent by RP-HPLC equipped with a diode-array detector. A Kromasil C18 column (200 mm x 4.6 mm i.d., 7 microns) was used with a mobile phase of methanol-acetonitrile-water (40:40:20, volume ratio) containing 0.02 mol/L KH2PO4 at pH 2.7 and UV detection at 280 nm. The samples were dissolved with the mobile phase by ultrasonic method. The recoveries of triclosan were from 94.2% to 102.2% and the RSDs were from 2.2% to 3.0%. The method is simple, rapid, accurate and reproducible. The concentrations of standards and samples did not change evidently after storage at 54 degrees C for 14 d and at 37 degrees C for 90 d. The results showed that triclosan has a good stability.

Background: Transgenic animals have become valuable tools for both research and applied purposes. The current method of gene transfer, microinjection, which is widely used in transgenic mouse production, has only had limited success in producing transgenic animals of larger or higher species. Here, we report a linker based sperm-mediated gene transfer method (LB-SMGT) that greatly improves the production efficiency of large transgenic animals., Results: The linker protein, a monoclonal antibody (mAb C), is reactive to a surface antigen on sperm of all tested species including pig, mouse, chicken, cow, goat, sheep, and human. mAb C is a basic protein that binds to DNA through ionic interaction allowing exogenous DNA to be linked specifically to sperm. After fertilization of the egg, the DNA is shown to be successfully integrated into the genome of viable pig and mouse offspring with germ-line transfer to the F1 generation at a highly efficient rate: 37.5% of pigs and 33% of mice. The integration is demonstrated again by FISH analysis and F2 transmission in pigs. Furthermore, expression of the transgene is demonstrated in 61% (35/57) of transgenic pigs (F0 generation)., Conclusions: Our data suggests that LB-SMGT could be used to generate transgenic animals efficiently in many different species.