Rescue of angiotensinogen-knockout mice.

Angiotensinogen, the precursor of angiotensins I and II, is a critical component of the renin-angiotensin system that plays an important role in regulating blood pressure and electrolyte homeostasis. Genetically altered mice lacking angiotensinogen (Agt-KO) showed an expected phenotype, such as marked hypotension, but unexpected ones including abnormal kidney morphology, reduced survival rates of newborns, and impaired blood-brain barrier function after cold injury. To examine whether disruption of the angiotensinogen gene is responsible for the observed phenotypes, we generated a line of mice heterozygous for the mouse angiotensinogen gene under the control of a mouse metallothionein-I promoter (MT-Agt) and crossmated transgenic mice with Agt-KO mice. The resulting mice (MT-Agt(+/-)/Agt(-/-):MT-Agt/KO) produced the plasma level of angiotensin I comparable to that of wild-type mice, and the mutant phenotypes were rescued. These results indicated that the resultant phenotypes due to the genetic deficiency of mouse angiotensinogen can be corrected by restoring angiotensinogen and angiotensin I in the circulation.

[Influence of T-593 on the recurrence and relapse of cryocautery-induced gastric ulcer in rats: sequential observation with an endoscope and histological evaluation].

We investigated the influence of T-593, a novel anti-ulcer agent, on the recurrence and relapse of cryocautery-induced gastric ulcer in rats, in comparison with the action of famotidine and ranitidine. The drugs were administered from the 7th to the 119th day and then discontinued to the 190th day after induction of gastric ulcer. The healing, recurrence and relapse process of gastric ulcer was sequentially observed with an endoscope. In the control group, the reduction of ulcer index was observed until the 76th day after ulcer induction followed by aggravation, suggesting the recurrence and relapse occurred on cryocautery-induced gastric ulcer in rats. In the famotidine and ranitidine groups, the recurrence and relapse occurred after cessation of administration. The recurrence and/or relapse rate of T-593 was lower than those of other drugs. In the histological measurement, the grades of heterotopic regenerated gland and inflammatory cell infiltration of T-593 was lower than those of the control and other drugs in the ulcer area. From these results, it is concluded that T-593 induces ulcer healing with a lower recurrence and/or relapse rate of ulcers than other conventional H2-antagonists, and T-593 may thus be a useful anti-ulcer drug for clinical therapy.

[Effect on 5'-deoxy-5-fluorouridine (5'-DFUR) of pyrimidine nucleoside phosphorylase (PyNPase), matrix metalloprotease and serum IAP values. Hokuriku Colorectal Cancer Chemotherapy Study Group].

PyNPase activity, MMPs activity and serum IAP values were measured in tumor tissues from colorectal cancer patients who had been divided into two groups, one given preoperative 5'-DFUR and the controls. PyNPase activity of the preoperative administration group was approximately equivalent to that of the controls. In the control group, correlations were assessed between PyNPase activity and activities of MMP1 and MMP3. To assess the effect of 5'-DFUR on the activity of MMPs, we divided patients into two groups, a high and a low PyNPase activity group. Although there was no correlation with MMPs activity of the preoperative administration group and the control group in the low PyNPase activity group, the activities of MMP1 and MMP9 of the control group were significantly higher in the high PyNPase activity group. Moreover, the serum IAP value of the administration group was significantly lower than that of the control group. These results indicated that PyNPase activity was thus suggested to be somehow related to MMPs activity and serum IAP values.