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Abstract: The clinical efficacy of hepatocyte growth factor (HGF) in tissue repair can be greatly enhanced by high affinity, biocompatible drug carriers that maintain the bioactivity and regulate release at the target site. We produced 0.5–3.0μm fragmin (low molecular weight heparin)/protamine microparticles (F/P MPs) as carriers for the controlled release of HGF. F/P MPs immobilized more than 3μg of HGF per mg of MPs and gradually released the absorbed HGF into the medium with a half-release time of approximately 5days. Compared with HGF alone, HGF-containing F/P MPs substantially enhanced the mitogenic effect of HGF on cultured human microvascular endothelial cells, by prolonging the biological half-life, and its conjugation to F/P MPs protected HGF from heat and proteolytic inactivation. F/P MPs disappeared 8days after subcutaneous injection in mice, suggesting that they are rapidly biodegraded. Furthermore, the number of large (diameter ⩾200μm or containing ⩾100 erythrocytes) and medium (diameter 20–200μm or containing 10–100 erythrocytes) lumen capillaries 8days after injection of HGF-containing F/P MPs was significantly higher than that after injection of HGF or F/P MPs alone. Furthermore, the number of small (diameter ⩽20μm or containing 1–10 erythrocytes) lumen capillaries was significantly higher 4days after injection of HGF-containing F/P MPs. This increased angiogenic activity of HGF in vivo is probably due to both sustained local release and protection against biodegradation by the F/P MPs. Thus, F/P MPs may be useful and safe HGF carriers that facilitate cell proliferation and vascularization at sites of tissue damage. [Copyright &y& Elsevier]

Summary: Background: In Japan, a major type of home-related hypersensitivity pneumonitis (HP) is summer-type HP, which is caused by Trichosporon asahii (T. asahii) or Trichosporon mucoides. Some patients with home-related HP test negative for antibodies against Trichosporon; yet, a causative mold antigen cannot be identified. Methods: We analyzed 19 patients with home-related HP, 8 healthy volunteers, and 35 patients with other diseases. We extracted DNA from cell pellets of bronchoalveolar lavage fluid (BALF), amplified the DNA by PCR using Trichosporon-specific primers or other fungus-specific primers, and cloned as well as sequenced the PCR amplicon. Other primers used were specific for Acremonium chrysogenum, Aspergillus fumigatus, Aspergillus niger, Fusarium napiforme, Humicola fuscoatra, Penicillium corylophilum, and Pezizia domiciliana. Results: We detected Trichosporon DNA (n = 17) and F. napiforme DNA (n = 2) by PCR in 19 patients with home-related HP; however, these species were not identified in healthy volunteers. After sequencing of the PCR amplicon for Trichosporon species, we identified T. asahii (n = 11), Trichosporon japonicum (n = 1), and Cryptococcus uzbekistanesis (n = 4). Conclusion: We could detect fungal DNA in BALF cell pellets from patients with home-related HP. These data suggest that this method might be useful to detect antigens responsible for home-related HP. [Copyright &y& Elsevier]