Electrospun poly(ɛ-caprolactone) scaffold for suture-free solder-mediated laser-assisted vessel repair.

BACKGROUND AND OBJECTIVE: The addition of poly(lactic-co-glycolic) acid (PLGA) scaffolds to liquid solder-mediated laser-assisted vascular repair (sLAVR) has been shown to increase soldering strength significantly. Unfortunately, the fast degradation of PLGA is associated with adverse effects such as acidity of the degradation products. This study investigated the possibility of using electrospun poly(ɛ-caprolactone) (PCL) as reinforcement material in scaffold and solder-mediated LAVR (ssLAVR). MATERIALS AND METHODS: In vitro sLAVR of 10-mm arteriotomies (n = 62) was performed on 0.3- to 0.6-cm diameter porcine carotid arteries with a 670-nm diode laser. The solder contained 50% bovine serum albumin (BSA) and 0.1-0.7% methylene blue (MB) as a chromophore. The soldering strength was studied as a function of PCL-scaffold thickness, scaffold-fiber diameter, MB concentration, number of laser passes, and different sLAVR techniques. Leaking-point pressures (LPPs) were measured with a fluid-infusion technique. RESULTS: The highest mean ± SD LPP (749 ± 171 mm Hg) was produced by the ssLAVR modality that included the sheathing of the arteriotomy with 30 µL solder containing 50% BSA and 0.5% MB, followed by application of the PCL scaffold (mean ± SD thickness of 187 ± 9 µm and 14-µm fiber diameter) and irradiation with two consecutive continuous-wave laser passes. CONCLUSIONS: The study demonstrated the potential applicability of an electrospun PCL scaffold as reinforcement material in ssLAVR. Soldering strength was dependent on the scaffold physical properties, chromophore concentration, the number of laser passes, and the ssLAVR technique.

Toxicity study of a new camptothecin anti-cancer agent CKD-602 in dogs: 4-week continuous intravenous dose by infusion pump and 4-week repeated intravenous dose.

In evaluating toxicity, one of the most important factors is the administration method, because it can affect the exposure and absorbance level of the test article, and, consequently, influence the interpretation of toxicity test results. Continuous intravenous (IV) administration is a widely used administration method for anti-cancer drugs in clinical settings. Previous studies have reported the toxic effects of the test article following repeated IV dosing of CKD-602, a novel camptothecin-derivative anti-tumor agent that was developed by Chong Kun Dang Pharmaceutical Corporation in Seoul, Korea. However, CKD-602-related toxicities induced by IV infusion administration have not yet been evaluated, although the drug is more widely used in clinical settings. In the present study, CKD-602 was administered using a continuous IV infusion pump and using repeated IV administration at doses of 0, 0.003, or 0.01 mg/kg/day for 4 weeks to compare and evaluate the drug-induced toxicities using the two different administration methods. Higher mortality, more severe clinical symptoms, increased complete blood count, serum biochemistry, and histopathology were demonstrated when CKD-602 was administered using the 4-week continuous IV infusion pump method compared with the repeated IV administration method. Based on these results, we conclude that the administration of CKD-602 using the 4-week continuous IV infusion pump method can elicit more severe toxicity than that using 4-week repeated IV dosing method. Thus, more attention should be paid to the administration of CKD-602 using continuous IV infusion in the clinical setting.

Histamine release induced by dendroaspis natriuretic peptide from rat mast cells.

Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure similar to that of the natriuretic peptide family. The natriuretic peptide family is known to induce histamine release from human and rat mast cells, but there are no published data concerning the effects of DNP on histamine release from mast cells. The purpose of this study is to investigate whether DNP induces the histamine release from rat peritoneal mast cells (RMPCs) and to determine the mechanism of DNP-induced histamine release from RPMCs. After treatment of RPMC with DNP, mast cell degranulation was observed, and calcium uptake and histamine release were measured. DNP released the histamine, induced the mast cell degranulation, and increased the calcium uptake of RPMCs, in a dose-dependent manner. The results indicate that DNP can increase Ca-uptake and induce histamine release.

A TGF-beta-inducible cell adhesion molecule, betaig-h3, is downregulated in melorheostosis and involved in osteogenesis.

Melorheostosis is a rare bone disease characterized by linear hyperostosis and associated soft tissue abnormalities. The skin overlying the involved bone lesion is often tense, shiny, erythematous, and scleodermatous. In order to look for genes differentially expressed between the normal and involved skin, we cultured skin fibroblasts from the skin lesions of several afflicted patients, and identified differentially expressed genes by reverse dot-blot hybridization. We found that the genes human TGF-beta-induced gene product (betaig-h3), osteoblast-specific factor 2, osteonectin, fibronectin, and type I collagen were all downregulated in the affected skin fibroblasts, with betaig-h3 the most significantly affected. The expression of betaig-h3 was induced by TGF-beta in both affected and normal fibroblasts. In an effort to determine the mechanism of bone and skin abnormalities in melorheostosis, we made recombinant betaig-h3. Both immobilized and soluble recombinant betaig-h3 proteins with or without an RGD motif inhibited bone nodule formation of osteoblasts in vitro. Taken together, our results suggest that altered expression of several adhesion proteins may contribute to the development of hyperostosis and concomitant soft tissue abnormalities of melorheostosis, with betaig-h3 in particular playing an important role in osteogenesis.

Atrial natriuretic peptide induces rat peritoneal mast cell activation by cGMP-independent and calcium uptake-dependent mechanism.

Atrial natriuretic peptide (ANP), a 28 amino acid basic polypeptide, is known to induce histamine release from human and rat mast cells in vitro and cause a wheel formation in rat skin. However, cellular events associated with histamine release are not clearly understood. In this study, we have examined the calcium flux and cGMP formation associated with histamine release in the ANP-treated mast cells. ANP, in vitro, induced mast cell degranulation and histamine release in a dose-dependent manner. ANP also induced an enhanced calcium uptake into cells and increased the cellular level of cGMP in mast cells. A high level of calcium in the media caused an inhibition of ANP-dependent histamine release but enhanced the level of intracellular cGMP of mast cells. ANP inducing a dose-dependent increase in vascular permeability of rat skin was confirmed by the extravasation of the circulating Evans blue. The results indicate ANP induced the histamine release and an increase in vascular permeability through mast cell degranulation in cGMP-independent and calcium uptake-dependent manner.