Cross-reactive mechanism for the false elevation of free triiodothyronine in the patients treated with diclofenac.

We report three cases of patients exhibiting a false elevation of serum free triiodothyronine (FT3) as a result of a cross-reaction with diclofenac. The first case is a 66-yr-old woman with a long history of rheumatoid arthritis (RA). The patient was receiving diclofenac for the treatment of her RA. The patient was subsequently diagnosed as having thyroid papillary adenocarcinoma and received a subtotal thyroidectomy. After the operation, the patient exhibited postoperative hypothyroidism except for a gradual elevation of FT3. The other two patients also exhibited an elevated serum FT3 level after the administration of diclofenac. Serum FT3 levels in these patients decreased to normal or below normal after diclofenac administration was discontinued. In the first case, the elimination of immunoglobulin from the sera using polyethylene glycol precipitation did not reduce the FT3 level. In our hospital, Vitros ECi (enhanced chemiluminescence enzyme immunoassay) system and Vitros FT3 kit were used for FT3 assay. The patient's FT3 levels were normal or below normal when they were measured using other FT3 kits. FT3 was also detected when diclofenac was dissolved in a phosphate buffered saline. Therefore, we concluded that a cross-reaction between FT3 and diclofenac was the mechanism causing the false elevation of FT3 in these patients.

Antihepatotoxic actions of Cochlospermum tinctorium rhizomes.

The antihepatotoxic activity of the rhizomes of Cochlospermum tinctorium was investigated using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Because the methanol and ethanol extracts of C. tinctorium rhizomes exhibited antihepatotoxic effects, the former was fractionated in order to elucidate the active constituents. Polyphenol compounds (gallic and ellagic acids) were detected in the active fractions and may account for much of the antihepatotoxic activity. Carotenoids could also be implicated in the activity of the total extracts.

Assay methods for antihepatotoxic activity using peroxide-induced cytotoxicity in primary cultured hepatocytes1.

Conditions were investigated to devise IN VITRO assay methods for antihepatotoxic activity using peroxide-induced damage in primary cultured rat liver cells. Utilizing linoleic acid peroxide, benzoyl peroxide, cumene hydroperoxide and adenosine diphosphate/Fe (3+), satisfactory assay procedures were established. Some natural products known to exert liver-protective effects IN VIVO were screened to reveal that glycyrrhetinic acid, glycyrrhizin, cynarin, silybin and desoxypodophyllotoxin showed similar antihepatotoxic activity in these four assay methods.

Effect of cyclic AMP on mesaconitine-induced analgesia in mice.

The effects of cyclic AMP, dibutyryl cyclic AMP, theophylline, isoproterenol and propranolol on mesaconitine (MA)-induced antinociception in mice were investigated employing the tail flick and acetic acid-induced writhing methods for the evaluation of antinociceptive activity. MA-induced antinociception was significantly potentiated by cyclic AMP and dibutyryl cyclic AMP. The phosphodiesterase inhibitor theophylline also significantly potentiated the MA-induced antinociception. Further, MA-induced antinociception was markedly increased by a beta-adrenoceptor agonist, isoproterenol, and reduced by a beta-adrenoceptor antagonist, propranolol. These results suggest that the antinociceptive action of MA is potentiated through cyclic AMP and stimulation of the central beta-adrenergic system.

Mechanism of inhibitory action of mesaconitine in acute inflammations.

Mesaconitine (MA) inhibited carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice. Hind-paw edema produced by subplantar injection of histamine, serotonin and prostaglandin E1 was suppressed by MA, indicating that it elicits the antiinflammatory activity at the early exudative stage of inflammations. However, MA did not affect the biosynthesis of the prostaglandins. Trazoline and propranolol had no effect on the inhibitory activity of MA on carrageenin-induced hind-paw edema. MA when administered i.c. at the doses where it shows marked analgesic activity produced dose-dependent antiinflammatory responses on paw edema produced by carrageenin and on vascular permeability accelerated by acetic acid and agar. The inhibitory activity of morphine on carrageenin-induced paw edema failed to be potentiated by the concurrent administration of MA, demonstrating that the mechanism of the antiinflammatory activity of MA involves the central nervous system.

Structure of methyl adenophorate and triphyllol, triterpenoids of Adenophora triphylla var. japonica roots.

From the crude drug "shajin", the roots of Adenophora triphylla var. japonica, two novel triterpenoids, methyl adenophorate and triphyllol, have been isolated and these structures have been determined as those represented by formula I and II, respectively, on the basis of chemical and physical evidence.

Antiinflammatory principles of Aconitum roots.

The methanol extracts of Aconitum roots have shown inhibition of increased vascular permeability induced by acetic acid and of hind paw edema produced by carrageenin in mice. The extract of A. carmichaeli has been fractionated, monitored by the capillary permeability test, to yield the aconitines as active principles. The aconitines have inhibited the increased vascular permeability induced by acetic acid in mice peritoneal cavity and that induced by histamine in rat intradermal sites, and the hind paw edema formation induced by carrageenin n rats and mice at low doses. The benzoylaconines have exhibited inhibitory effects of the aforementioned acute inflammations but at higher doses. The aconitines have reduced the granulation tissue formation of the chorio-allantoic membrane of the chick embryo. On the other hand, the Aconitum alkaloids have elicited no effects on the ultraviolet erythema formation in guinea pigs at lower doses than the lethal ones and failed to show positive responses on the vascular permeability in the granuloma pouch and on adjuvant arthritis in rats at the doses employed.