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Biomedical subjects

M Hisaoka

Publications and source records attributed to M Hisaoka.

81 records · Page 5Linked to original sources

Kinetics of drug action in disease states. II. Effect of experimental renal dysfunction on phenobarbital concentrations in rats at onset of loss of righting reflect.

The purpose of this investigation was to determine if renal dysfunction is associated with an alteration in the concentration-pharmacologic activity relationship of phenobarbital (PB). Adult female rats (congruent to 200 g) were pretreated with uranyl nitate or subjected to bilateral ureteral ligation to produce renal dysfunction. Saline-injected and sham-operated rats, respectively, served as controls. PB (0.824 mg/min) was infused i.v. until the animals lost their righting reflex (LRR). Renal dysfunction reduced the total dose of PB required to produce LRR, the concentrations of total and free (unbound) PB in serum and the concentrations of PB in brain and cerebrospinal fluid at onset of LRR. Results were quantitatively similar in both experimental models of impaired renal function. Concomitant infusion of p-hydroxyphenobarbital (the major metabolite of PB) and PB in rats with uranyl nitrate-induced renal dysfunction had no effect on the PB concentrations at onset of LRR. When PB was infused at different rates (either 0.412, 0.824, 2.04 or 4.12 mg/min), rats with renal dysfunction had increasing concentrations of PB at onset of LRR with increasing infusion rate, not only in serum and brain but also (unlike normal rats) in cerebrospinal fluid. Thus, renal dysfunction is associated with increased sensitivity to PB and with a change in the kinetic relationship between PB in cerebrospinal fluid and in the biophase.

Acute Kidney Injury↗

Studies on liposome-encapsulated carboquone II. Effect of liposomal encapsulation of carboquone on distribution and clearance in animals.

The effects of encapsulation of carboquone (CQ) in the liposomes were investigated on the plasma clearance and tissue distribution of CQ in rabbit and rat. CQ-Liposome, the liposomes in which CQ was encapsulated, was prepared by the method described in a previous report. By intravenous administration at the same dose. CQ-liposome showed approximately three times higher plasma concentration than free CQ in rabbit and rat. However, prolonged release from liposomes or stabilization of CQ in plasma was not observed by encapsulation. The distribution to lung and reticuloendothelial-rich organs such as liver and spleen was enhanced, but on the contrary the distribution to the peripheral tissues such as muscle and skin was decreased. In rats pretreated with drug free liposomes, high plasma CQ concentration was obtained after intravenous administration of CQ-liposome. From these results, it is considered that the large parts of CQ-liposome is distributed into reticuloendothelial system (RES) and RES is saturable with liposomes. And it is also presumed that the high plasma concentration obtained after intravenous administration of CQ-liposome, would be caused by altering the tissue distribution of CQ by encapsulation.

Animals↗

Studies on liposome-encapsulated carboquone. III. Enhancement of lymphatic transport of carboquone by encapsulation.

To examine the possibility of utilizing liposomes as drug carriers of carboquone (CQ), an antitumor agent, effects of encapsulation on transport into lymphatics have been studied. Enhancement of lymphatic transport of CQ was obtained by the administration of liposome encapsulated CQ (CQ-liposome) into abdominal cavity in thoracic duct cannulated rats. And also, the enhancement of CQ transport into regional lymph nodes belong to gastrointestinal tract was also demonstrated in normal rats. When CQ-liposome was administered intravenously or intramuscularly, however, excellent transport into lymphatics was not recognized. Various pharmaceutical formation such as emulsions and oily solution failed to produce as high a lymph level as CQ-liposome. These results show that liposome may represent an effective system to deliver CQ into lymphatics by intraperitoneal administration.

Animals↗

Studies on liposome-encapsulated carboquone. IV. Enhancement of antitumor activity of carboquone against Ehrlich ascites carcinoma by encapsulation.

The antitumor effects of liposome-encapsulated carboquone (CQ-liposome) were studied following intraperitoneal administration into mice bearing Ehrlich ascites carcinoma (EAC). CQ-liposome showed nearly 3 times superior efficiencies to parent CQ (free CQ) in the growth inhibitory effect on EAC cells inoculated in mice, and also showed almost the same toxicity as free CQ in normal mice. CQ-liposome prolonged the life span of EAC bearing mice about 2 times that of free CQ. In the results of electrophoresis, it was found that CQ-liposome and EAC cells had positive and negative surface charges, respectively. These observations suggest that CQ-liposome is a favorite delivery system to enhance the efficiency of CQ to EAC in mice. One of the reasons for its excellent effect may be explained by an easy contact of CQ-liposome with EAC cells because of its opposite surface charges.

Animals↗

Determination of carboquone in plasma and ascites by high performance liquid chromatography after intravenous and intraperitoneal administration in man.

A new method for the determination of carboquone (CQ) in human plasma and ascites by high performance liquid chromatography has been developed. The method is sensitive enough to determine levels as low as 1.0 ng per 1.0 ml of plasma or ascites. The average recovery of CQ from these samples was 89.3 +/- 0.9% (n = 5, mean +/- SD). The method consists of 2 steps, 1) extracting CQ from human body fluids with chloroform and 2) quantization of CQ by chromatography using a mu-Bondapak C18 column, monitored at 340 nm, 2,5-Diethyleneimino-3,6-dimethylbenzoquinone was used as the internal standard. Using this analytical method, the concentration-time profiles of CQ in human body fluids after intravenous and intraperitoneal administrations were obtained. It was recognized that intraperitoneal administration of CQ was advantagenous for the treatment of peritonitis carcinomatosa since an effective concentration could be maintained in ascites for about 6 hr.

Ascitic Fluid↗

Myxoid leiomyosarcoma of the uterus. Report of a case with cytologic findings.

BACKGROUND: Myxoid leiomyosarcoma is a rare variant of uterine sarcoma, exhibiting malignant biologic behavior despite the absence of cytologic atypia and of significant mitotic activity. CASE: A 20-year-old female was referred with a cystic pelvic mass. At laparotomy, the tumor, weighed 2,200 g and originating in the left lateral uterine wall, was removed. Microscopic examination revealed well-differentiated smooth muscle cells without atypia and with a few mitotic figures in the copious myxoid matrix, suggesting myxoid leiomyosarcoma. Three years following laparotomy, an irregular mass around the uterus was noted on sonographic examination, suggesting local recurrence. Two years and six months later, the second operation was performed, and a locally recurrent, multicystic tumor weighing 3,500 g was excised. The histopathology was similar to that of the primary tumor. Cytologic findings on imprint material from the tumor revealed a few isolated or sheet like small cells consisting of spindle and polygonal cells with round and oval nuclei. Cytologic atypia was also minimal. CONCLUSION: Myxoid leiomyosarcoma should be included in the differential diagnosis of smooth muscle neoplasia.

Adult↗