[Can 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) evaluate the renal function without blood sampling?: consensus report from multicenter study].

A multicenter study was undertaken in Japan to evaluate the correlation between the percentage of renal uptake of 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) estimated by the count-based gamma camera method and the blood clearance of 99mTc-MAG3. Twenty four centers were enrolled and 172 cases were finally analyzed in this study. The renal clearance of 99mTc-MAG3 (TER) was obtained by using a single blood sample taken at 44 min after injection. Comparison of TER and renal uptake provided a coefficient of correlation of 0.874; suggesting that sufficiently accurate quantification of renal function could be obtained from the renal uptake estimate by the gamma camera method. This study also showed that the comparison of renal function might be feasible among patients under the same protocols, although precise and careful consideration is required in each center.

[Effect of high calcium intake on blood pressure and intracellular pH, Na(+)-H+ exchange activity in stroke-prone spontaneously hypertensive rats].

Effect of high calcium (3%) intake on blood pressure and intracellular pH, Na(+)-H+ exchange activity, cytosolic free calcium concentration in stroke-prone spontaneously hypertensive rats (SHRSP-Ca) is compared with sex-, ag-matched SHRSP and WKY rats without high calcium intake. The results showed that high calcium intake significantly suppressed increase in blood pressure and decreased cytosolic free calcium concentration after it was given to SHRSP-Ca for 6 weeks, while plasma calcium was increased. The intracellular pH tended to be in the normal range of WKY rats. Na(+)-H+ exchange activity was slightly decreased. Correlationship between blood pressure and intracellular pH, Na(+)-H+ exchange activity and cytosolic free calcium concentration were discussed.

The effect of alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory drug, on leucocyte migration in rat carrageenan pleurisy.

KME-4,alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-buty rolactone was found to reduce the accumulation of leucocytes and exudate volume in the rat carrageenan pleurisy model. When administered orally 1 h before carrageenan, KME-4 (3-10 mg kg-1) induced a degree of inhibition of leucocyte migration almost equal to that of indomethacin (3-10 mg kg-1) in both 5 h and 24 h pleurisies. Furthermore, KME-4, when administered orally 5 h after the carrageenan, inhibited both monocyte numbers and exudate volume in a 24 h pleurisy and was more effective than indomethacin and BW755c which inhibited only monocyte migration. These results suggest that KME-4 has a differential anti-inflammatory activity. Dexamethasone (0.25 mg kg-1) showed strong inhibition of total cell numbers and exudate volume.

Inhibition of polymorphonuclear leukocyte 5-lipoxygenase and platelet cyclooxygenase by alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolacto ne (KME-4), a new anti-inflammatory drug.

The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory compound, on arachidonate lipoxygenase and cyclooxygenase was investigated. KME-4 showed a dose-dependent inhibition of 5-lipoxygenase activity in both the cytosol (IC50: 0.85 microM) and ionophore A23187-stimulated cells (IC50: 11.5 microM) of guinea pig peritoneal polymorphonuclear leukocytes. KME-4 was also found to inhibit rabbit platelet cyclooxygenase (IC50: 0.44 microM), but had no inhibitory effect on platelet 12-lipoxygenase at concentrations up to 100 microM, whereas BW755C inhibited both enzymes in the same range of concentrations. The results indicate that KME-4 is a dual 5-lipoxygenase and cyclooxygenase inhibitor which is different from BW755C in affecting 12-lipoxygenase. These effects may provide information for understanding the pharmacological activity of KME-4.

Pharmacological properties of a new anti-inflammatory compound, alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolacto ne (KME-4), and its inhibitory effects on prostaglandin synthetase and 5-lipoxygenase.

The pharmacological effects of a new anti-inflammatory compound, alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its inhibitory effects on arachidonate prostaglandin synthetase and 5-lipoxygenase activities were examined. KME-4 showed anti-inflammatory activity. It was less active than indomethacin, but more active than naproxen and ibuprofen in carrageenin-induced paw edema in rats; and it was less active than indomethacin, equipotent as naproxen, but more active than ibuprofen in granuloma formation in rats. The ulcerogenic activity of KME-4 was weaker than indomethacin and naproxen, but stronger than ibuprofen in starved rats. The ratio of UD50 stomach to ED30 carrageenin edema or to ED25 granuloma for KME-4 showed higher values than those of the reference drugs. KME-4 showed antipyretic activity in yeast-induced fever in rats. It also inhibited platelet aggregation induced by arachidonic acid and protected rabbits from arachidonic acid-induced death. Furthermore, KME-4 was found to be equipotent in inhibiting both prostaglandin synthetase and 5-lipoxygenase activities of rat basophilic leukemia cells, unlike indomethacin, naproxen and ibuprofen. It also inhibited the prostaglandin synthetase activity of bovine seminal vesicle. The present findings indicate that KME-4 may be a new type of anti-inflammatory drug with dual prostaglandin synthetase and 5-lipoxygenase inhibition.