Active oxygens (O₂^-, H₂O₂, ⋅OH, OCl^-, ¹O₂, LOO⋅, LO⋅) are involved in various inflammatory processes. Leukocytes generate O₂^- and H₂O₂ to attack the invaded bacteria and xenobiotics, but excess production results in inflammation. Antigen-antibody complex, cytokines etc. also generate active oxygens. Clinically using non-steroidal anti-inflammatory drugs (NSAIDs, diclofenac sodium, indomethacin etc.) inhibit leukocyte O₂^- production. Immune diseases, ischemia and atherosclerosis develop organ inflammation via formation of active oxygens. Vascular tone-regulating EDRF (NO⋅) is decomposed by O₂^- and proteinases may react to the proteins which were degenerated by active oxygens. Free and modified SODs are under animal and clinical trials as well as antioxidant derivatives.

抄録全体を表示

Using an air pouch type allergic inflammation model in rats, roles of arachidonate metabolites in inflammatory responses were investigated in order to define characteristics of allergic inflammation in rats, and to get further insight into a methodology for suppression of inflammation from a veiw point of arachidonic acid metabolism. Biochemical and pharmacological analysis revealed following results; (1) Peptide-leukotrienes do not play any significant role in vascular permeability increase in anaphylaxis phase. (2) Leukotriene B₄ also plays no role in neutrophil infiltration, suggesting that participation of lipoxygenase products in inflammatory responses is negligible in rats. (3) In contrast, antagonists of platelet activating factor (PAF) efficiently suppressed neutrophil infiltration into the inflammatory locus indicating that PAF plays a significant role for neutrophil infiltration. (4) Prostaglandin E₂ participates in vascular permeability increase at a definite period, and in stimulation of neutrophil infiltraltion by suppressing histamine production at the inflammatory locus. (5) Cyclooxygenase inhibitors suppress vascular permeability and neutrophil infiltration. Suppression of neutrophil infiltration by cyclooxygenase inhibitors is mediated by stimulation of histamine production through inhibition of prostaglandin E₂ biosynthesis. Histamine suppresses neutrophil infiltration by acting on histamine H₂ receptors of neutrophils.
Finally, present situation and point at issue for suppression of inflammation through regulation of arachidonic acid metabolism is discussed.

抄録全体を表示

In this study was selected 43 cases of jaw cysts with various state of infection. The cysts were measured fluids of lipidperoxides and bone components.
Non-infection cyst fluids showed low values of the leukocyte and PC-OOH, LOO radicals, but showed high value of pO₂. It indicated that O₂^- and⋅OH were inhibited.
Infection cyst fluids showed high values of Hb and Fe²⁺ concentration. Infection cyst wall showed high values of PC-OOH and LOO radicals. Bone of surrounding cyst showed weakly absorption of PO₄^3-.
In the result, it is suggested that the growth of jaw cyst was caused by the damage of microcirculation in cyst walls. Therefore, it was concerned with increased free radicals by infection in the cyst cavities.

抄録全体を表示

We studied the effects produced in vitro by minocycline (MINO), aminobenzyl penicillin (ABPC) and cefotiam (CTM) on polymorphonuclear leukocytes (PMN) chemotax. PMN chemotaxis in the presence of these antibiotics was evaluated using the Boyden chamber technique and polarization assay.
The following results were obtained: CTM brought about a significant increase of PMN chemotaxis at the therapeutic dose (10, 100μg/ml), MINO already reduced PMN chemotaxis significantly at concentra-tion as low as 1μg/ml and ABPC didn't influence PMN chemotaxis at concentration up to 100μg/ml in both methods. Furthermore according to checkerboard assay, it was proved that CTM worked as a chemokinetic factor.

抄録全体を表示

To investigate the function and morphology of peripheral blood leukocyte (PBLs) in adjuvant-induced arthritis rats, time course study were performed. Both adherence and NBT reducing capacity of PBLs were enhanced depending on the development of pathogenesis on this arthritis. PBLs adherence was increased with maximum at 10 days (17 fold vs control) and the other at 14 days (4 fold vs control) for NBT reducing capacity after adjuvant innoculation. In morphological examination by scanning electron micrographs, numerous platelets interacted with the surface of PBLs was observed from 10 days after adjuvant innoculation. But these cell-cell interaction was not shown in normal rats. These results suggest that both activation of PBLs interaction among blood cells such as platelet was associated with the development of adjuvant-induced arthritis rats and the analyses of PBLs function and morphology may be useful for evaluating the inflammation process or drugs, such as NSAID or DMARs, in adjuvant-induced arthritis rats.

抄録全体を表示

Using human leukocytes, we tested the two electric instruments such as “basic water producing electric instrument” and “high voltage electric treating instrument” which have been applied for promoting health and treating the disorders, and human hand palmar energy (called “Kikoh” in Japan and China) all of which emit electro-magnetic wave (i.e. far infrared ray) with wave length of 4-14 μm, in order to confirm whether they actually show the effect on the human cell activity; the effect of these instruments and hand palmar energies on normal or diseased human leukocyte functions was examined. The effect of electric instruments on human leukocytes was examined using the leukocytes obtained after the electric current was pulsed to the human normal or diseased subjects, and that of “Kikohshi” was tested by covering their hand palmars over the test tubes containing leukocyte suspensions.
The result revealed that they significantly increased [Ca²⁺] i in neutrophils, phagocytosis and reactive oxygen species (ROS), O₂^- generation by neutrophils, and blastogenetic response of lymphocytes to mitogens. Although other three did not show significant effect, palmar hand of one“Kikohshi”, Mr. Nukui significantly increased chemotactic activity of neutrophils from both normal and diseased subjects. Present study suggests that these electric instruments and “Kikohshi” actually potentiate cell functions possibly by increasing cellular [Ca²⁺] i.

抄録全体を表示

In order to clarify the induction of hepatic metallothioneins (MTs) as an acute phase reactant by endotoxin (lipopolysaccharide; LPS) shock further, induction of MT-I and MT-II by LPS was determined by high-performance liquid chromatography coupled with atomic absorption spectrophotometry. Rats were injected with LPS (5 mg/kg) and the hepatic concentrations of Zn-MT-I and Zn-MT-II were determined at 0, 3, 6, 12, 18, and 24 hours after the injection. Time-course experiments showed that MT-II predominantly accumulated in comparison to MT-I. The MT-II increased rapidly at 6 hours after the injection, reached the maximum at 18 hours and then decreased gradually. All of these values were significantly different from those values of MT-I. These results suggest that MT-II may play some role in acute phase response during endotoxin shock.

抄録全体を表示

Thrombin activity was investigated in the synovial fluids (SF) obtained from the patients with osteo-arthritis, by measuring prothrombin (pro-Th), antithrombin III (ATIII) and thrombin-AT III complex (TAT) levels. Pro-Th level in the SF was 10% of the plasma levels, while TAT level was one hundred times higher than that in the plasma. These results suggest that, in SF, thrombin was frequently formed and may be concerned with fibrin formation and endothelin release in arthritis.

抄録全体を表示

Ampiroxicam is a newly developed NSAID for the treatment of RA and its characteristic feature is that it is a prodrug of piroxicam.
Of the 141 patients enrolled in the study, only 12 patients (8.5%) dropped out of the study. All the parameters of morning stiffness, grip strenght, the number of painful joints and swollen joints, ADL and Lansbury activity index showed a significant improvement as compared with pretreatment conditions. A slight improvement was noted in sedimentation rate as well as CRP but this was not significant.
The final global improvement in all the patients was 64.3% for slight to marked improvement. Patient assessment was also improved significantly as compared with pretreatment conditions.
Side effects were few and observed in 16 patients (11.4%) out of 140 who were assessed for the safety of the drug. None of the side effects observed was severe. Abnormal laboratory test values were observed in 10 patients (7.1%) .
The final overall safety rating was 83.6% for safety and 92.9% for almost safe and safe combined.
The foregoing results allow us to conclude that ampiroxicam is a safe and useful drug in the longterm therapy of patients with RA.

抄録全体を表示