Ryoetsu Abe

Magnetic microcapsules for targeted delivery of anticancer drugs

To achieve targeted distribution of anticancer drugs with sustained activity, ferromagnetic ethylcellulose microcapsules containing an anticancer drug, mitomycin C (FM-MMC-mc), were prepared by a method based on phase separation principles. Two prototypes of FM-MMC-mc were made: one with the drug as the core and zinc ferrite on its capsular surface (outer type); the other with both the drug and zinc ferrite as the core (inner type). Both preparations provided a sustained-release property and a sensitive response to conventional magnetic force, although certain differences in the release rate of drug, magnetic responsiveness, and particle size were found between the two dosage forms. Animal studies showed that the magnetic microcapsules could be magnetically controlled in the artery and urinary bladder. VX2 tumors in the rabbit hind limb and urinary bladder were successfully treated with magnetic control of FM-MMC-mc. Pharmacokinetic study revealed that the targeting of the microcapsules markedly enhanced the drug absorption into the surrounding tissues for a prolonged period of time. The results indicate the feasibility and effectiveness of the magnetic microcapsules as a targeted drug delivery system.

The oxalate level in ultrafiltrate fluid collected from a dialyzer is useful for estimating the plasma oxalate level in hemodialysis patients

BackgroundPatients on chronic hemodialysis are likely to develop secondary hyperoxalemia. It is, however, difficult to measure plasma oxalate levels. To measure plasma oxalate levels, rapid plasma separation, deproteinization, and acidification are essential in preventing the formation of oxalate and the deposition of calcium oxalate within the test tube. The present study was undertaken to examine whether the oxalate level in dialyzer ultrafiltrate is potentially useful for estimating plasma oxalate levels.MethodsIn nine patients on chronic hemodialysis, the plasma, after deproteinization with a filter, and the ultrafiltrate from the dialyzer before hemodialysis were acidified to a pH level of less than 3, followed by the measurement of oxalate levels by ion chromatography. Also, oxalate levels were compared between acidified and non-acidified ultrafiltrates from the dialyzer. In the second part of the study, seven patients on chronic hemodialysis receiving erythropoietin therapy, in whom the ferritin level was more than 300 ng/ml and transferrin saturation was less than 25%, were intravenously administered ascorbic acid, 100 mg, three times a week, after each dialysis session to facilitate the utilization of stored iron. This treatment was continued until the serum ferritin level decreased to a level below 300 ng/ml (for 3 months, at a maximum). The oxalate level in the dialyzer ultrafiltrate after this treatment was compared with that before treatment.ResultsThe mean ± SE oxalate level in the dialyzer ultrafiltrate was 45 ± 6 μmol/l, essentially equal to the plasma oxalate level (46 ± 7 μmol/l). The plasma oxalate level had a significant positive correlation with the dialyzer ultrafiltrate oxalate level (plasma oxalate level = 0.99 × dialyzer ultrafiltrate oxalate level + 1.5; r = 0.95; P < 0.0001). The oxalate level in the acidified ultrafiltrate (45 ± 6 μmol/l) did not differ significantly from that in the non-acidified ultrafiltrate (45 ± 6 μmol/l). The mean ± SE duration of ascorbic acid administration was 64 ± 13 days. The hemoglobin level remained unchanged at 9.6 ± 0.4 g/dl, whereas the serum iron level increased significantly, from 34 ± 2 μg/dl to 43 ± 4 μg/dl (P < 0.05), and serum ferritin levels decreased significantly, from 645 ± 219 ng/ml to 231 ± 30 ng/ml after the treatment (P < 0.05). The oxalate level in the acidified ultrafiltrate showed no significant change after ascorbic acid administration (31 ± 8 μmol/l vs 47 ± 7 μmol/l).ConclusionsIn patients on chronic hemodialysis, the oxalate level in acidified ultrafiltrate from the dialyzer was found to be useful for estimating the plasma level of non-protein-bound oxalate. When administering ascorbic acid to hemodialysis patients, the plasma oxalate level can be monitored using this method.

CYTOLOGICAL DIAGNOSIS FROM RANDOM MUCOSAL BIOPSIES USING IMPLINT TECHNIQUE DURING OPERATION

A purpose of mucosal random biopsy of urinary bladder is to get informations about the extent of cancerous lesion and the existence of rest of cancer. For the purpose of determining the care range of the operation and postoperative treatments by getting these informations during the operation, we drew up stamp cytological preparations for mucosal random biopsy of urinary bladder performed during TUR-Bt, and examined potency of application of this method to quick diagnostics. First of all, 15 times of transurethral resections of bladder cancers were performed on 14 cases, and 19 of imprint preparations were made from the excised tumor materials during operation. Then the accuracy rate of the rapid cytology was evaluated based on permanent preparations that were made simultaneously. The accuracy rate of the intraoperative rapid cytology was 84.2%. Next, a similar procedure was performed on 68 materials of random biopsy during the above-mentioned operation. The accuracy rate of imprint cytology was 73.5%. The relatively low accuracy rate of rapid cytology must be attributed to diagnostic difficulty noted when dealing with Papanicoloau class 3. For all above, it was suggested that rapid implant cytology during operation must be applicable to quick diagnostics.

Two-dimensional analysis of the cardiac shadow as an index of overhydration in patients with renal failure.

慢性透析患者54例を対象として, 胸部X線写真正面像心陰影の面積を測定し, これをもとに心陰影面積の平方根/最大胸郭横径 (%) を算出し, 二次元心胸郭比 (2°CTR) とした. これを従来から用いられているCTR (心胸郭比) と比較して, 慢性透析患者におけるDW (dry weight) 推定における有用性を検討した.全症例をDWが高く設定されていることが臨床的に明らかな症例群 (A群: 22例) とそれ以外の症例群 (B群: 32例) に分けたところ, 2°CTR値は前者では平均49.3%, 後者では平均44.2%と, A群がB群に比べ推計学的に有意 (p<0.0001) に高値を示した. また, A群において2°CTR値およびCTR値が正常上限を越えた症例の比率は, 前者が95.5%, 後者が86.4%と前者で有意 (p<0.0001) に高く, DW設定に際しては2°CTRがCTRに比較してより有用であると思われた.

Arterial chemoembolization with microencapsulated anticancer drugs as a treatment for malignant tumors.

Seven hundred and fifty nine patients with malignant tumors were treated by intra-arterial infusion with microencapsulated anticancer drugs from 1978 to 1986. Mean age of the patients was 60.3 yrs(13-88). Fifty seven percents of patients had stage 4 tumor and 41%were grade 3-4 in performans status. The target organs subjected to the treatment were liver(310), kidney(177), bladder(100), prostate(41), lung(39), pelvic organs(13), bone(4)and the others (75). Median doses of drugs in microcapsules were 20 mg for MMC, 40 mg for PEP and 60 mg for CDDP. Of 455 measurable tumors, 113(25%)showed a substantial reduction of greater than 50%. In 508 evaluable patients, side effects frequently recognized were fever(57%)and local pain(50%)shortly after the treatment. However, these side effects were generally mild and temporary. Gluteal skin ulcer occured in 33 patients(21%)who underwent hypogastric arterial infusion, but improved within a few months. Only one patient died of treatment-related cause. These results suggested that microcapsule therapy can be successfully applied to a variety of tumors with low morbidity and low mortality, and also can be combined with other treatments in multidisciplinary therapy.