Angiogenesis or neovascularization describes the formation of new blood vessels. It is critically associated with not only physiological phenomena such as ovulation and wound healing but also pathological ones such as tumor, inflammation and immune reaction. The process of neovascularization consists of sequential steps e.g. chemotaxis, tube formation and proliferation of vascular endothelial cells (ECs) .
Various biological substances such as heparin-binding EC growth factors (acidic and basic fibroblast growth factors), transforming growth factor-α & β, angiogenin and platelet-derived EC growth factor were reported to enhance in vitro neovascularization. Inflammatory prostaglandins, prostacyclin and cytokines also enhanced neovascularization when examined by corneal micropocket technique. In contrast, some cartilage components and protamine inhibit angiogenic factor-induced neovascularization. It is, therefore, suggested that the above mentiond biological substances uniquely regulate both physiological and pathological angiogenesis. In therapeutic relevance, cortisone inhibits in vivo neovascularization in the presence of heparin. Disease-modifying antirheumatic drugs such as gold salts, D-penicillamine, bucillamine, lobenzarit disodium and methotrexate suppress both EC proliferation and corneal neovascularization.
These drugs may, therefore, suppress disease activity through inhibition of local neovascularization. Deeper understanding of the regulation of angiogenesis will shed light on the therapeutic approaches to so-called angiogenic diseases such as tumor and inflammation.

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Nerve growth factor (NGF) is a neurotrophic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is known of the structural and functional characters of NGF, whose gene has recently been cloned. Despite of its name, NGF has been shown to elicit broader biologic effects on non-neuronal tissues. For example, NGF causes augmentation of lymphocyte mitogenesis, induces shape changes in platelets and degranulation of peritoneal mast cells, and accelerates wound healing. We explored the effects of NGF on human and murine hemopoietic colony formation, with particular emphasis on basophil/mast cell colonies. We also found that NGF enhanced the survival, phagocytosis and superoxide production of murine neutrophils.
These observations raise the possibility of even broader biologic actions of NGF on both allergic and non-allergic inflammatory processes.

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We have isolated a cytotoxic factor from the submandibular glands of male and female BALB/c mice using Sephadex G-50 gel filtration chromatography and reverse-phase HPLC. SDS-PAGE and amino acid sequence analysis revealed that the cytotoxic factor was mouse glandular kallikrein (mGK) . The cytotoxic factor was the mixture of mGK-6 and -9 in male mice and mGK-6 in female mice.
The purified mGK showed a cytotoxicity against mouse thymocytes in a dose-dependent manner and a enzyme activity of tissue kallikrein.

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Employing interferon gamma activated human monocyte cell line, THP-1, we have demonstrated that luminol dependent chemiluminescence (CL) and lucigenin dependent CL are simultaneously elicited by phagocytosis of murine IgG2a coated SRBC, an immune complex that specifically binds to FcR I on THP-1. Conversely, only lucigenin dependent CL and no luminol dependent CL has been elicited by unphagocytosable FcR I stimulus. The results suggest that NADPH oxidase system and myeloperoxidase-halide system are triggered upon stimulation of a single class of IgG Fc receptor, and that the former system is activated merely upon FcR I stimulation and the latter upon phagocytosis mediated by the same receptor.

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On the process of the wound healing after operation, it has been known that some blood coagulation factors and plasma proteins had some important roles and significances. In addition, it has been known that protease-antiprotease system was closely related to the wound healing. In this paper, we examined the effect of urinastatin, an urinary trypsin inhibitor which was a polyvalent protease inhibitor, on the change of fibrinogen, factor XIII and fibronectin level in the circulating blood of rabbits after operation.
In administered group, 100, 000 units/ml of urinastatin was continuously injected to rabbits until 10 days after the operation. Level of fibrinogen in administered groups at 5, 6 and 12 day after the operation was significantly higher than that in non-admini-stered group (p<0.05) .
Activity of F. XIII in administered groups at 5 days after the operation was significantly higher than that in non-administered group (p<0.05) . Level of fibronectin in administered group was not significantly different from that in non-administered group.
From the result of increased level of fibrinogen, fibronectin and increased activity of F. XIII, it was suggested that administration of urinastatin gave the accelerating effect to the wound healing.

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We examined the effect of glycyrrhizin (GL) on the production of platelet-activating factor (PAF) from mouse hepatic sinusoidal endothelial cells. GL was shown to significantly suppress the production of PAF from the mouse sinusoidal endothelial cells stimulated with calcium ionophore A 23187.
This result suggests that GL may act on sinusoidal endothelial cells and have an influence on the local hepatic inflammatory reactions by the suppression of PAF production.

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To the recent knowledge, it is possibly speculated that reactive oxygen metabolites (ROM) play a key role in the initiation and progression of glomerulonephritis. The present study was aimed to clarify where ROM are produced in the renal tissue, and whether para-amino benzoate sodium Mannoside, which is named K-MAP bring about a therapeutic effect on renal damage caused by ROM or not. The production of ROM was induced with the injection of 20-40 μg/animal of phorbol myristate acetate (PMA) .
The injection of PMA lead to massive proteinuria with severe morphological alterations in glomeruli and tubuli. ROM were visualized out in the glomerular and tubular cells by means of celium chloride staining method. K-MAP demonstrated significant effects against the proteinuria and pathological changes in the glomerulus of the experimental model.
From these results, we suggest that ROM participate in the progression of renal injury due to glomerulonephritis and K-MAP may have a therapeutic effect on it.

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To determine whether neutral endopeptidase (NEP) modulates substance P-induced increase in vascular permeability, we examined the effects of an NEP inhibitor and of other protease inhibitors on plasma extravasation induced by intradermal injection of substance P in guinea pig skin. The substance P-induced plasma extravasation was increased by an NEP inhibitor phosphoramidon. Other protease inhibitors, however, did not affect the response. SP_1-9, the primary degrading product of substance P by NEP, did not induce any significant plasma extravasation.
The results suggested that NEP modulates substance P-induced increase in vascular permeability in the skin.

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Loxoprofen sodium was administered to 28 patiens with rheumatoid arthritis who underwent surgical treatment and its concentrations in plasma, synovial membrane, muscle, and fat were studied. OH-derivate is the active metabolite of loxoprofen sodium, and it reached the maximum level in plasma and synovial membrane 2 hours after administration. Thus, a rapid increase of the drug level in the target tissue (synovial membrane) was observed.
The relative concentration ratio of the active metabolite in each tissue 4 hours after administration were as follows: plasma 1.0; synovial membrane 0.93; synovial fluid 0.91; muscle 0.40; and fat 0.09.
These results indicate that selective transfer of loxoprofen sodium into inflamed synoviall membrane and synovial fluid.

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CYA is an immunosuppressant, which is preferentialy used for organ transplantation. Recently, there has been frequent reports that CYA is effective for immunological disorders, such as RA, nephrotic syndrome etc.
A clinical trial was carried out in order to investigate the efficacy of CYA on thirty three patients with RA. The initial daily dosage of CYA was 3 mg/kg and later adjusted based on individual informations from clinical symptoms and adverse effects.
Statistically significant improvements were acknowledged in the number of swollen joints, grip strength, activities of daily living and serum concentration of CRP.
The main adverse effects were hypertrichosis, renal dysfunction and stomach pain. It was concluded that CYA was beneficial in management of RA patients.

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