Absorption, distribution and excretion of 14C-josamycin and 14C-josamycin propionate in rats (author's transl)]

Abosrption, distribution and excretion of 14C-josamycin (JM) and 14C-josamycin propionate (JM-P) were studied in rats by measuring both antibacterial activity and radioactivity. 1. In antibacterial activity, plasma and tissue concentrations of JM-P showed a similar tendency to those of JM. Those concentrations of JM reached a peak at 1 hour after administration with a subsequent rapid decrease, while the peak level of JM-P appeared 2 approximately 4 hours after administration and then fell down very slowly. 2. In radioactivity, oral administration of JM-P rapidly produced a very high plasma and tissue concentrations which were in lung, liver, kidney and spleen more than twice those of JM. These results showed that when given orally, JM-P is well absorbed with distributions at high concentrations especially in lung, liver, and kidney and spleen. 3. The ratios of bioactivity/radioactivity in JM administration were the highest in lung and the lowest in liver at 1 hour after. But those of JM-P were generally much lower than those of JM because of higher distribution of JM-P radioactivity into tissues. 4. Four days after oral administration of JM and JM-P, 23.1% and 21.8% of the given radioactivity were recovered respectively from urine. However, the antibacterial activities recovered were 0.40% for JM and 0.65% for JM-P. 5. Biliary recoveries of JM and JM-P were 17.2% and 12.1% of administered radioactivity 2 days after oral administration. On the other hand, 0.47% of JM and 0.17% of JM-P were excreted into bile as antibacterial activity. These results showed that JM and JM-P were excreted into rat urine and bile as some metabolites with less biological activity. 6. The amounts of JM and JM-P recovered from feces were 75.7% and 60.2%, respectively, of the orally given radioactivity. The amount of radioactivity recovered from expiration air was about 1% of either orally given JM or JM-P.     

Mechanism of histamine release by alpha-chymotrypsin from isolated rat mast cells.

Alpha-chymotrypsin (CT) was modified chemically and physically by the treatments with diisopropyl fluorophosphate, L-(1-tosylamide-2-phenyl) ethylchloromethylketone, hydrogen peroxide and heat. After these treatments, CT lost or decreased both the enzymic activity and ability of releasing histamine from rat mast cells. Ca++ was essential for histamine release by CT, while it enhanced only slightly the enzymic activity. Process of histamine release by CT could be separated into two stages: CT-dependent but not Ca++-dependent, and Ca++-dependent but not CT-dependent. The activated state of mast cells produced by CT decayed rapidly at 37 degrees C in the absence of Ca++, but these cells responded to Ca++ by adding CT once again, suggesting reconstitution of cell membrane structure affected by CT. Isoproterenol, epinephrine, prostaglandin E1, and dibutyryl-cyclic AMP (0.01-0.1 mM) did not inhibit release of histamine induced by CT. Neither theophylline (0.01-0.1 mM) alone nor the combinations of these cyclic AMP-active agents with theophylline inhibited the release of histamine. But, in the presence of papaverine (0.01-0.1 mM) a marked, dose-dependent inhibition was observed. These data suggest that 1) release of histamine by CT from rat mast cells is causally related to its hydrolytic activity, 2) this activity causes a reversible change on mast cell membrane which probably facilitates Ca++-influx through the cell membrane, and 3) there are subtle differences among CT, compound 48/80 and antigens concerning the effect of cyclic AMP-active agents in histamine-releasing mechanisms in mast cells.     

Projections from the parietal cortex to the brain stem nuclei in the cat, with special reference to the parietal cerebro-cerebellar system

Direct projections from the anterior portions of the parietal cortex of the cat to the brain stem nuclei, especially those sending fibers to the cerebellum, were investigated by the Nauta-Gygax and Fink-Heimer methods. Following unilateral lesions of the anterior portions of the middle suprasylvian and/or lateral gyri, a significant amount of pericellular degeneration was found almost entirely ipsilaterally in the rostral levels of the red nucleus and its vicinities, and in the pontine nuclei. Projection fibers to the pontine nuclei appeared to extend over several longitudinal, columnar zones in the pontine gray. Fibers from the anterior portion of the lateral gyrus were observed mainly in the paramedian and lateral nuclei, and those from the middle suprasylvian gyrus in the ventral, paramedian and lateral nuclei. Degeneration in the nucleus reticularis tegmenti pontis of Bechterew was slight, and found bilaterally with ipsilateral predominance. The significance of the anterior portion of the parietal cortex of the cat as a link of cerebro-cerebellar loops was discussed.     

Effect of steroid on antiemetic for side effect of anticancer chemotherapy

The side effect of anticancer agents such as nausea and vomiting frequently interrupt chemotherapy. To reduce these side effects, 5-hydroxytryptamine (5-HT3) receptor antagonist or metoclopramide is administered combined with steroid. In this study, we examined the effect of 5-HT3 receptor antagonist on the frequency of nausea and vomiting in a male cancer patient treated with/without steroid. This patient in his sixties had esophageal cancer (stage IV). He was administered nedaplatin 100 mg/day for 1 day and then 5-fluorouracil (5-FU) 750 mg/day for 5 days combined with radiotherapy (60 Gy) as one cycle of this chemotherapy. In the first cycle, 5-HT3 receptor antagonist was administered, and in the second, the antagonist was administered after treatment with steroid. The blood levels of total bilirubin, GOT, GPT, BUN, Cre, Na, K and Cl were stable normally during both cycles of the chemotherapy, indicating that the hepatopathy and nephropathy which cause nausea and vomiting did not occur in these periods. The frequency and period of the nausea and vomiting were one-third decreased, respectively, by the combination of 5-HT3 receptor antagonist and steroid.     

A case of successful treatment using "wrapping therapy" for huge hepatocellular carcinoma

This case is about a male in his 50's. In May 2004, he consulted a nearby doctor with abdominal pain and was pointed out a huge mass in the liver. He was diagnosed as hepatocellular carcinoma over 10 cm in diameter with chronic hepatitis type B. Because the tumor concurred with intra-hepatic metastasis along with lymph node metastasis, we planned transhepatic arterial embolization (TAE) as a first choice of treatment and performed twice. However, because of the tail inside part of the tumor was supplied from the gastroduodenal artery (GDA) and right gastroepiploic artery (RGEA) which were nutrient arteries, an effective TAE was impossible. The enhancement lesion that seemed viable was shown by enhanced CT. Therefore, a wrapping therapy (surgical decollateralization+silicon membrane sheeting) was performed under laparotomy for the purpose of cutting off blood supply to the part of the viable lesion in August of the same year. The tail inside part of the tumor that seemed viable fell into necrosis by wrapping alone, and the serum PIVKA-II level decreased within normal limit. As of ten months after the treatment, the patient is still alive without aggravation.