Intestinal absorption of calcium from calcium ascorbate in rats.

The intestinal absorption of calcium (Ca) from Ca ascorbate (Ca-AsA) was investigated in normal rats. Each animal was perorally administered either 5mg (low dose) or 10mg (high dose) of Ca in 1ml of distilled water as Ca-AsA, Ca carbonate (CaCO3), or Ca chloride (CaCl2), which were intrinsically labeled with 45Ca using 45CaCl2. The amount of radioactivity in plasma was measured periodically up to 34h after dosing, and pharmacokinetic parameters were calculated from the radioactivity in plasma. The time taken to reach the maximum 45Ca level (Tmax) did not differ among the three groups. The area under the plasma 45Ca level/time curve (AUCinfinity) value for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups. The radioactivity at Tmax (Cmax) for the Ca-AsA group was significantly higher than those for the CaCO3 and the CaCl2 groups for the low dose, and comparable with or significantly higher than those for the CaCl2 and CaCO3 groups for the high dose. Similar results were observed for whole-body 45Ca retention. Radioactivity in the femur 34h after dosing was the highest in the Ca-AsA group and the lowest in the CaCO3 group. The rank order of solubility in water, the first fluid (pH 1.2, JP-1) of JPXIII disintegration medium, acetate buffer solution (pH 4.0), triethanolamine-malate buffer solution (pH 7.0) and ammonium chloride buffer solution (pH 10.0) at 37 degrees C was CaCl2 > Ca-AsA > CaCO3. In contrast, the rank order of the solubility in the second fluid (pH 6.8, JP-2) of JPXIII disintegration medium at 37 degrees C was Ca-AsA > CaCl2 > CaCO3. These results indicate that the absorbability of Ca from Ca-AsA is almost comparable with, or higher than, that from CaCl2 and significantly higher than that from CaCO3 because of its high degree of solubility in the intestine. Therefore, Ca-AsA would be useful as a Ca supplement with relatively high absorption from intestine.

A new approach to methotrexate and lipiodol suspensions for ectopic pregnancy: preliminary in vitro and animal experiments.

OBJECTIVES: To measure and evaluate the in vitro release of MTX from suspensions of methotrexate (MTX) and lipiodol (LPD), and to investigate the MTX concentration and fertility rate using an animal model. METHODS: This study was divided into three components: a) An in vitro Release Study, b) Animal Study No. 1 (concentration of tissue and plasma levels), and c) Animal Study No. 2 (fertility rate after MTX suspension). RESULT: The releasing rate in vitro was more rapid with MTX-S (MTX dissolved in saline) than with either MTX-LPD (MTX dissolved in lipiodol) or MTX-LPD-PC (MTX suspended in lipiodol and phosphatidylcholin, i.e., MTX suspension). The tissue concentration tended to be higher with an MTX suspension than with MTX-S. There was no significant difference in the fertility rate or the nidation index among the 3 groups (Groups 1, 2, and 3). CONCLUSION: The injection of an MTX suspension is useful for increasing the tissue concentration and maintaining the long-term effectiveness of MTX, and this technique might offer a new approach in the treatment of ectopic pregnancy (EP) or in second-line therapy for persistent EP.

[Long-term administration of carmofur as a post-operative adjuvant chemotherapy for cervical adenocarcinoma. Cervical Adenocarcinoma Cooperative Research Association].

Cervical adenocarcinoma and adenosquamous cell carcinoma are low in radiation sensitivity, and the prognosis is said to be inferior to that of squamous cell carcinoma. Eleven facilities nationwide participated in the historical control study on the recurrence prevention effect of carmofur (HCFU) administered at 300 mg/day for more than two years postoperatively as an adjuvant chemotherapy to patients with cervical adenocarcinoma or adenosquamous cell carcinoma for which radical operation is possible. Registered for the study was a total of 252 patients: 77 patients for whom administration of carmofur was begun during the period from January 1987 and March 1989, 71 patients (control 1) who were treated for the cancer after January 1982 but did not receive adjuvant chemotherapy, and 104 patients who received adjuvant chemotherapies with other than carmofur (control 2). In analyses with the Kaplan-Meier method, the carmofur administration group demonstrated a better cumulative survival rate and disease free rate than control 1 (no adjuvant chemotherapy), suggesting carmofur was effective in preventing the recurrence of cervical adenocarcinoma and adenosquamous cell carcinoma.

[A multicenter cooperative study on supplementary chemotherapy of uterocervical cancer. The Kyushu UFT Study Group of Uterocervical Cancer].

A randomized study was carried out by means of multicentered cooperation in respect to 5-FU and UFT administration, which was used as the supplementary chemotherapy after treatment of uterocervical cancer. Five years later, the improvement in prognosis was examined. Out of all the cases with radical operation + supplementary chemotherapy as well as with radical operation + postoperative radiotherapy + supplementary chemotherapy, 98 cases were ratable. The analysis of 98 cases led to no significant difference in the survival rate between the 5-FU administration group and the UFT administration group. As to the cases with supplementary chemotherapy + postoperative radiotherapy only, the survival rate was significantly higher in the UFT administration group than in the 5-FU administration group. During the administration, severe adverse side effects developed neither in the 5-FU administration group nor in the UFT administration group. These results suggest that UFT may be useful as a factor in supplementary chemotherapy of uterocervical cancer in combination with radiotherapy.

Thiol-mediated redox regulation of lymphocyte proliferation. Possible involvement of adult T cell leukemia-derived factor and glutathione in transferrin receptor expression.

The proliferative response of PBMC to PHA, Con A, OKT3 mAb and IL-2-dependent proliferation of PHA-blasts was examined in a thiol-free environment (cultured in a L-cystine- and GSH-free medium). [3H]TdR incorporation assay and cell cycle analysis revealed that stimulated PBMC could not enter the S phase when deprived of these thiol compounds. In thiol-free cultures, an increase in intracellular free Ca2+ concentration and IL-2R alpha-chain/p 55 (Tac) induction was still observed, whereas transferrin receptor induction was markedly reduced, suggesting that the proliferative response of mitogenically stimulated PBMC was arrested in the late G1 phase in which transferrin receptor is induced. In GSH-depleted cultures, a similar reduction of the proliferative response of PBMC and PHA-blasts was observed when the concentration of L-cystine was lowered, in a dose-dependent manner. Each reduction or loss of proliferative response was partially restored by supplementation of 2-ME or adult T cell leukemia-derived factor (ADF)/human thioredoxin which is considered to be an endogenous dithiol-reducing factor. L-Cystine transport analysis showed that mitogenically stimulated PBMC and PHA blasts incorporated L-cystine, whereas resting PBMC did not. Furthermore, ADF as well as 2-ME exhibited an enhancing activity on the L-cystine transport in PHA blasts. Together with the fact that L-cystine transport is a limiting step in glutathione synthesis, these findings suggest that GSH and ADF might cooperate in the thiol-mediated redox regulation process and might also play key roles in cell cycle (late G1 to S) progression of activated lymphocytes.