Sachiko Oh-ishi

Roles of kallikrein-kinin system in acute inflammation: Studies on high- and low-molecular weight kininogens-deficient rats (B/N-Katholiek strain)

Carrageenin-induced paw edema in HMW- and LMW-kininogens-deficient rats was significantly less than that in normal rats. There are three kiniogens, HMW-, LMW- and T-kininogens, in normal rat plasma, but B/N-Katholiek rat plasma contains only T-kininogen. The pretreatment with captopril, a kiniase II inhibitor, enhanced paw swelling of normal rats, but not that of the deficient rats, indicating that bradykinin released from HMW-kininogen may have a role for the swelling but T-kinin may not be released in this inflammation.

Pharmacological Demonstration of Inflammatory Mediators Using Experimental Inflammatory Models: Rat Pleurisy Induced by Carrageenin and Phorbol Myristate Acetate

Rat pleurisy induced by carrageenin or phorbol myristate acetate (PMA) was utilized for examination of the plasma exudation process of inflammation. Chemical mediators responsible for induction of vascular permeability increase were examined. In carrageenin-induced pleurisy, kinin and PGl2 were demonstrated as the main mediators, and in PMA pleurisy histamine, PGI2 and platelet-activating factor were the main mediators. These results indicate that different stimuli may activate different enzymatic processes to produce different mediators, but they may result in similar inflammatory reactions by action of these multiple mediators simultaneously released.

Detection of platelet-activating factor in exudates of rats with phorbol myristate acetate-induced pleurisy

PAF-likely activity, detected as aggregation of washed platelets, was found in the exudate of rats with pleurisy induced by phorbol myristate acetate (PMA, 1 nmol). At 30 min after the injection of PMA, 400-500 pg of PAF was detected in the pleural exudate. An extract of the exudate was made and analysed by HPLC and by rabbit platelet aggregation. The activity was characterized as that of PAF as a result of the inhibition seen with the PAF-antagonist CV-3988 and the loss of activity by treatment with phospholipase A2. Indirect evidence was previously reported in that CV-3988 suppressed the pleural fluid accumulation in the pleurisy induced by PMA. Taken together these facts it indicates that PAF could be an important mediator of acute inflammation, especially of the plasma exudation resulting from an increase in vascular permeability. Evidence that pleural cells produce PAF was also examined in an in vitro experiment. PAF was found in the supernatant and cellular fractions of the incubation mixture of the pleural cells from normal rats when stimulated by PMA (1 microM) or A23187 (5 microM), and the results indicate that the pleural cells produce PAF and release a portion of it.

Developmental and sexual differences of T-kininogen levels in rat plasma and liver

T-kininogen levels in plasma and liver microsomes were measured by radioimmunoassay in female and male rats of various ages. High levels of T-kininogen were found in plasma and liver of 1-day to 1-week old male and female rats and their mothers. The levels in newborns gradually decreased along with their development. In mature male rats the levels were as low as 1/5-1/2 of those in mature female rats. Treatment with estradiol increased the plasma and the liver levels of T-kininogen significantly in both sexes, but testosterone decreased the level in female rats and had no effect in male rats. These results suggest that sex hormones may regulate the physiological level of T-kininogen in rats.

Functionally active high molecular weight-kininogen was found in the liver, but not in the plasma of brown Norway katholiek rat

Plasma and liver levels of high molecular weight (HMW-) kininogen were assessed by a newly developed radioimmunoassay in B/N-Katholiek strain rats, which is congenitally deficient in plasma HMW- and low molecular weight (LMW-) kininogens. The plasma level of immuno-reactive HMW-kiniogen in this strain was about 4% of that of the normal strain, B/N-Kitasato, whereas its level in B/N-Katholiek liver was approximately 60% of that in normal strain liver. There was no significant difference of half-life of HMW-kininogen in the circulating blood between the deficient and normal rats. When secretion of HMW-kiniogen from the liver cells of the two strains was examined by primary culture of their hepatocytes, the hepatocytes from the deficient strain did not secrete HMW-kininogen in the medium. HMW-kininogens were isolated from the liver microsomal fractions of both strains by use of an immuno-affinity column. The isolated protein from B/N-Katholiek liver showed similar mobility on SDS-PAGE to that from normal rat liver, and had biological activities of HMW-kininogen purified from normal rat plasma, such as intrinsic blood clotting cofactor, thiol-proteinase inhibitor, and kinin precursor. These results indicate that the plasma deficiency in the B/N-Katholiek strain is due to a defect of HMW-kininogen secretion from the liver.

Application of heat- and steam-generating sheets to the lumbar or abdominal region affects autonomic nerve activity.

Effects of applying a heat- and steam-generating (HSG) sheet on peripheral hemodynamics and autonomic nerve activity were examined. An HSG sheet was applied to the lumbar or abdominal region. Measurements included skin temperature at the lumbar and abdominal regions and the fingertip, total hemoglobin, tissue oxygen saturation ratio (StO2), pupillary light reflex, changes in ECG R-R interval blood pressure and percutaneous electrogastrography (EGG). A heat-generating sheet without steam was used as the control. Based on the present findings, application of the HSG sheet to the lumbar or abdominal region may improve peripheral hemodynamics and inhibit sympathetic nerve activity, resulting in parasympathetic nerve activity dominance.