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Biomedical subjects

E Fujihira

Publications and source records attributed to E Fujihira.

At least 37 records · Page 2Linked to original sources

Peroxidative status of isolated hepatocytes from adjuvant arthritic rats.

Bleb-like protrusions frequently appear in the plasma membrane of the hepatocytes freshly isolated from adjuvant arthritic rats by the collagenase-perfusion method. These hepatocytes show reduced overall synthesis of phospholipids and triglycerides, decreased percentages of arachidonic acid present in the plasma membrane, microsomal membrane and bile canalicular membrane, decreased levels of soluble thiol compounds, and increased lipid peroxidation. The content of thiobarbituric acid reactive substances in liver tissue homogenate and the level of lipid peroxides in blood are significantly higher in adjuvant arthritic rats than in normal controls. These observations suggest that inflammation might cause enhanced membrane fragility and altered membrane-bound enzyme function in rat hepatocytes, probably due to an increasing tendency to lipid peroxidation.

Animals↗

Progressive foot swelling in BUF rats. A new animal model for screening of anti-inflammatory and anti-rheumatic drugs.

Buffalo rats of a low adjuvant-arthritis responder strain demonstrate a continually increasing swelling in the hind foot inoculated with mycobacterial adjuvant, characterized by extensive panostitis, new bone formation and long-delayed bony calcification. A rapid regression of foot swelling was produced by a three-day course of therapy with indomethacin (1 mg/kg) or with dexamethasone (0.1 mg/kg), but a definite rebound was followed soon after termination of the therapy. This recurrent episode occurred repeatedly in the second and third therapeutic trials with the anti-inflammatory drugs in the same animals. The 5 days treatment with either levamisole (5 mg/kg) or cyclophosphamide (5 mg/kg) prevented further increase in the swelling for a long time period after withdrawal of the drug, and enhanced bone mineralization.

Animals↗

Reduced drug metabolism in isolated hepatocytes from adjuvant arthritic rats.

Viable hepatocytes were isolated from the livers of rats with adjuvant arthritis by the collagenase-perfusion method and measured for activities of drug-metabolizing enzymes. These cells produced radioactive metabolites from 14C-aminopyrine and 14C-aniline to a much lesser extent than the control hepatocytes that were derived from pair-fed normal rats. On the other hand, 14C-aminopyrine was scarcely metabolized by non-parenchymal cells other than hepatocytes, even when incubated with those from control rats. Although there were no significant differences in cell yield, viability and oxygen consumption, the cellular uptake of indocyanine green was significantly slower in the arthritic hepatocytes than the control hepatocytes. Morphologically, the freshly isolated arthritic hepatocytes demonstrated the disappearance of the microvilli, the appearance of bleb-like protrusions in the plasma membrane and the widespread distribution of the rough endoplasmic reticulum associated with a relatively decreased area of the smooth endoplasmic reticulum in the cytoplasma. Biochemically, these cells showed a significantly higher RNA/DNA ratio and an ability to incorporate 14C-leucine into proteins more rapidly, as compared to the control hepatocytes. A possible relationship between the reduction of the drug metabolizing activity and the production of the acute phase proteins in rat hepatocytes after an inflammatory stimulus was discussed.

Aminopyrine↗

Hepatic drug-metabolizing enzyme activities and anti-inflammatory potency of hydrocortisone in rats with granulomatous inflammation.

Experimental granuloma pouches were induced in the dorsum of Sprague-Dawley rats by the subcutaneous injection of either carrageenin or agar. In the former inflammation model, the hepatic activities of aminopyrine N-demethylase and aniline hydroxylase and the contents of cytochromes P-450 and b5 were reduced significantly from control and pentobarbital sleeping time was prolonged. Hydrocortisone inhibited significantly the increased vascular permeability, exudation and proliferation of the carrageenin-induced granuloma in the daily, oral dose of 10 mg/kg for 3 days. On the other hand, the animals with agar granuloma pouch did not show any decline of the hepatic drug metabolism and a same dosage level of hydrocortisone showed substantially no inhibitory effect on the agar granuloma. Consequently, it is suggested that impairment of the hepatic drug metabolism may be responsible for the increased potency of hydrocortisone in the carrageenin-induced granuloma.

Agar↗

Intraperitoneal systemic anaphylaxis in the mouse. I. Age-dependence of fatal anaphylactic shock.

Following the i.p. challenge of a shocking dose of BSA from 9 days up to 133 days after the s.c. injection of BSA in CFA, fatal anaphylaxis was induced regularly in female ICR mice that had been given the immunizing antigen when 8 weeks old. These immunized mice provided an antiserum to BSA that had the capacity to transfer fatal shock to normal recipient mice at a minimum Ab-N dose of 8 microgram when the i.p. route for challenge was employed. The optimal dose-range of antigen and antibody in order to elicit fatal shock following the i.p. challenge was much broader than that obtained by i.v. injection. Age is critical in producing fatal shock in mice; a 100% fatal anaphylaxis never occurred in groups of 6- and 7-week-old recipient mice although those at 8 weeks and older were sufficiently sensitized by the amounts of antibody given.

Aging↗