Therapeutic angiogenesis induced by controlled release of fibroblast growth factor-2 from injectable chitosan/non-anticoagulant heparin hydrogel in a rat hindlimb ischemia model

The addition of non-anticoagulant heparin [periodate-oxidized (IO4) heparin] and fibroblast growth factor (FGF)-2 to a viscous water-soluble chitosan (CH-LA) aqueous solution produces an injectable FGF-2/CH-LA/IO4-heparin hydrogel. The purpose of this study was to examine the ability of the injected FGF-2/CH-LA/IO4-heparin hydrogel to induce vascularization and fibrous tissue formation. FGF-2/CH-LA/IO4-heparin hydrogels (100 microL of hydrogel consisting of 20 mg/mL of CH-LA, 2 mg/mL of IO4-heparin, and 50 microg/mL of FGF-2) were subcutaneously injected into the backs of wound healing-impaired diabetic (db/db) mice. Furthermore, the effect of percutaneous injection of FGF-2/CH-LA/IO4-heparin hydrogel at eight sites (25 microL/site) into ischemic left lower limbs of rats was examined from day 4 to at least day 28 postinjection. The injection of FGF-2/CH-LA/IO4-heparin hydrogels into the backs of db/db mice resulted in significant increases in blood vessel formation, significant vascularization, and fibrous tissue formation near the injection site. Injection of FGF-2/CH-LA/IO4-heparin hydrogel into ischemic left lower limbs of rats also significantly recovered and increased blood flow and blood oxygen in the calf and thigh. These results indicate that the controlled release of biologically active FGF-2 molecules from FGF-2/CH-LA/IO4-heparin induces angiogenesis and possibly collateral circulation in db/db mice and the ischemic limbs of rats.     

Sex-related effect of cadmium on hepatic cytochrome p-450, drug-metabolizing enzymes and 5-aminolevulinic acid synthetase and heme oxygenase in the rat

The effect of cadmium on hepatic cytochrome P-450 containing drugmetabolizing enzymes, δ-aminolevulinic acid synthetase (ALA synthetase) and heme oxygenase activity in both male and female rats was examined to define the nature of sex differences in response. In male rats injected i.p. with a single dose of cadmium chloride (1.25 mg Cd/kg body weight) there was a reciprocal relationship between the decrease of cytochrome P-450 levels and drug-metabolizing enzymes and the increase of heme oxygenase activity for up to 120 h. Hepatic ALA synthetase activity was initially decreased and returned to control levels at 24 h. In female rats, cadmium initially produced similar effects to those seen in male rats, but these were of shorter duration except for the increase of heme oxygenase activity. In addition, ALA synthetase activity was slightly increased at 24 h and 48 h.The results suggest that the sex differences in response reside mainly in the duration of the metal effect on these hepatic enzymes.     

Excision of papillary endocardial tumor

We report the eighth case of surgical removal of a papillary endocardial tumor. The surgical approach was aided by intraoperative two-dimensional echocardiography. The tumor was attached to the chorda tendinea of the mitral valve and was successfully removed via a left atrial approach.     

Functional relationships between Rad18 and WRNIP1 in vertebrate cells

The WRNIP1 protein interacts with WRN, the product of the causative gene for Werner syndrome. Mutation of the Saccharomyces cerevisiae gene MGS1, the yeast counterpart of WRNIP1, confers synthetic lethality with mutation of RAD18. To examine the functional relationship between WRNIP1 and Rad18 in higher eukaryotic cells, we generated WRNIP1-/-/-/RAD18-/- lines from chicken DT40 cells and compared them with single mutant cell lines. Unlike the corresponding yeast mutant, WRNIP1-/-/-/RAD18-/- cells are viable but grow more slowly than single mutants and wild type cells, and they show an additive or synergistic elevation in the frequency of sister chromatid exchanges. As reported, WRNIP1-/-/- cells and RAD18-/- cells are moderately and severely sensitive to camptothecin (CPT), respectively. Unexpectedly, the severe CPT sensitivity of RAD18-/- cells is slightly suppressed by disruption of the WRNIP1 gene.     

Morphogenesis of plasmatic arterionecrosis as the cause of hypertensive intracerebral hemorrhage

Summary The morphogenesis of the vascular lesions, which were considered to be the immediate cause of hypertensive intracerebral hemorrhage, was morphologically studied in autopsy cases. The direct cause of the hemorrhage was the rupture of the intracerebral microaneuysms resulted from the plasmatic arterionecrosis. The arterionecrosis was predominantly present in the intracerebral arteries of approximately 150 µ diameter, especially in the external branches of the arteriae corporis striati mediae in the putamen, and characterized by medial smooth muscle cell loss, blood plasma insudation in the intima, histolysis of the internal elastic lamina and intimal collagenous fibers, fibrin deposition (fibrinoid degeneration) in the intima, and luminal dilatation. The morphogenesis of the arterionecrosis was the development of histolysis as well as fibrinoid degeneration caused by blood plasma insudation in the wall of the intracerebral arteries with preceding necrosis and loss of medial smooth muscle cells and subsequent fibrous intimal thickening with dilated lumina. Intracerebral microaneurysms were also formed by the plasmatic arterionecrosis in a narrow sense, in which histolysis due to blood plasma insudation had occurred, but fibrin (fibrinoid substance) deposition in the intima had not yet arisen.     

Long-term follow-up results after reconstruction of the mitral valve by leaflet advancement.

In this study, we discuss the clinical results of mitral leaflet advancement performed on 29 patients over the past 10 years and attempt to determine the indication. Preoperative diagnosis of mitral valve lesion consisted of mitral regurgitation in 21 patients and mitral stenosis in 8 patients. Mitral valve repair was applied to the anterior mitral leaflet in 2, the posterior mitral leaflet in 25, and bilateral leaflets in 2 patients. Reoperation was performed on 13 patients, and 1 patient died of renal failure immediately after reoperation. No reoperation was needed for 96.6% of the patients at 1 year, 89.5% at 5 years, 75.0% at 8 years, 63.8% at 10 years, and 52.6% at 15 years postoperatively. At reoperation, the repaired mitral leaflet was found to be calcified in 3 patients more than 9 years after the initial operation. Of the 12 survivors without reoperation, mitral stenosis associated with regurgitation was obvious in 6 patients. Of the 21 patients with preoperative mitral regurgitation, 90.0% showed no deterioration at 5 years, 79.7% at 8 years, and 69.1% at 10 years. On the other hand, for the 8 patients with mitral stenosis, the rates were 87.5% at 1 year, 62.5% at 5 years, 50.0% at 8 years, and 25% at 10 years. Our results suggest that mitral leaflet advancement shows satisfactory results in patients with mitral regurgitation but is not successful for patients with mitral stenosis in the long term because the repaired valve tends to be stenotic in the late postoperative period.     

Surgical treatment of infective endocarditis in childhood--report of 3 cases

This is the case report of 3 surgical patients with infective endocarditis in childhood. Case 1: A 8 year-old boy was admitted with high fever and congestive heart failure. Aureus staphylococci were identified by blood culture. Echocardiogram showed a vegetating mass on the posterior mitral leaflet. This patient was cured by emergency mitral valve replacement during the active phase of infection. Case 2: A 3 year-old girl was admitted with infective endocarditis related to VSD. Viridans streptococci were identified by blood culture. Echocardiogram showed a vegetating mass on the septal tricuspid leaflet. After successful antibiotic therapy, this patient underwent the closure of VSD and tricuspid valvuloplasty. Case 3: A 7 year-old boy was admitted with infective endocarditis related to VSD. Aureus staphylococci were identified with blood culture. Echocardiogram showed a vegetating mass on the anterior tricuspid leaflet and moderate tricuspid regurgitation. After successful antibiotic therapy, this patient underwent the closure of VSD and tricuspid valvuloplasty. We believe that echocardiography plays an important role in the diagnosis and management of infective endocarditis and that tricuspid valvuloplasty is the method of first choice in treatment of the patient with regional tricuspid infective endocarditis.