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Biomedical subjects

H Iguchi

Publications and source records attributed to H Iguchi.

At least 181 records · Page 10Linked to original sources

[Effect of thrombin on hematuria after operation for benign prostatic hyperplasia].

The control of intra- and postoperative hemorrhage is as significant a problem following prostatectomy as postoperative urinary tract infection. We made a trial use of a solution of thrombin in continuous bladder lavage to control postoperative hemorrhage. A group of 21 patients with benign prostatic hyperplasia were treated by the thrombin lavage, with a group of 20 similar patients as controls. The treated group comprised 5 patients operated on by suprapubic, 11 by retropubic and 6 by transurethral prostatectomy, and the control group consisted of 6 patients operated on by suprapubic, 8 by retropubic, and 6 by transurethral prostatectomy. The thrombin lavage was, as a general rule, performed by lavaging the bladder with a solution of thrombin in physiological saline containing 100 units in each ml through an indwelling 3-way Foly catheter continuously for 24 hours following operation. There was no significant difference in the duration of macroscopic hematuria following operation by any operating technic between the control and the treated grove. The duration of microscopic hematuria was significantly shorter in the patients operated on by suprapubic prostatectomy and treated with thrombin than in the control group similarly operated on, and also tended to be reduced in the patients operated on by retropubic prostatectomy and treated with thrombin, compared with the controls similarly operated on. There was no significant difference in the duration between the patients operated on by transurethral technic. No particular adverse reactions to the thrombin lavage were observed.

Aged↗

[A case of cholangiocarcinoma treated by transcatheter arterial embolization].

A case history with a 2 year and 10 month survival, involving a peripheral cholangiocarcinoma that had been treated 3 times by transcatheter (TAE) and radiotherapy is discussed. The main cholangiocarcinoma markedly decreased in size and was found to contain many small calcified deposits after the 3 episodes of TAE.

Adenoma, Bile Duct↗

Elevation of plasma 7B2 (a novel pituitary protein) in cord blood at obstetrical delivery and the possible correlation with GH.

Plasma 7B2-immunoreactivity (7B2-IR) concentrations in umbilical artery (UA), umbilical vein (UV) and maternal vein (MV) were measured by RIA at the time of obstetrical delivery at term. Plasma 7B2-IR concentrations (Mean +/- SEM) in UA (N = 12), UV (N = 16) and MV (N = 16) were 725 +/- 69, 699 +/- 64 and 116 +/- 4.5 pg/ml, respectively. Plasma 7B2-IR concentrations in UA and UV were much higher than those in MV. There was no arterio-venous gradient between UA and UV. A trace amount of 7B2-IR (Mean +/- SEM, 226 +/- 16.8 pg/g tissue) was detected in the placental extracts. A statistically significant positive correlation (r = 0.7595, p less than 0.005) was found between plasma 7B2-IR and GH in the UV. Significant negative correlations between body weight of the neonates and plasma levels of GH (r = -0.6836, p less than 0.01) and 7B2-IR (r = -0.4939, p less than 0.05) were also apparent. When analyzing cord blood plasma using gel permeation chromatography and SDS-polyacrylamide gel electrophoresis, a major peak with an apparent molecular weight of 20,000 was observed. These findings suggest that 7B2-IR in UA and UV originates from the fetus and that 7B2-IR does not permeate through the placenta. The possibility of involvement of 7B2 in fetal growth warrants attention.

Chromatography, Gel↗

Age-related change in plasma concentration of 7B2 (a novel pituitary polypeptide) in normal humans.

Using a specific radioimmunoassay, we measured concentrations of plasma 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) in normal human subjects, patients with chronic renal failure and those with liver cirrhosis. Mean (+/- SEM) values of plasma 7B2-IR in normal healthy men and women were 55.8 +/- 1.2 pg/ml (n = 266) and 56.1 +/- 0.9 pg/ml (n = 408), respectively. The elevation of plasma 7B2-IR showed a relationship with age of the subjects, in both men (r = 0.39, t = 6.86, p less than 0.001) and women (r = 0.35, t = 7.44, p less than 0.001). Plasma 7B2-IR concentrations were elevated in patients with chronic renal failure (536 +/- 45 pg/ml, Mean +/- SEM, n = 10) as well as those in liver cirrhosis (95 +/- 10 pg/ml, Mean +/- SEM, n = 15) compared to values in normal subjects, suggesting that 7B2 is mainly eliminated through the kidney and is partly metabolized in the liver.

Adult↗

Presence of the novel pituitary protein "7B2" in bovine chromaffin granules: possible co-release of 7B2 and catecholamine as induced by nicotine.

We observed the presence of the novel pituitary protein "7B2" and its release in the bovine adrenal medulla. The 7B2 concentration (mean +/- SEM) in extracts of the bovine adrenal medulla was 952 +/- 155 pg/mg tissue (n = 6). 7B2 was distributed in the chromaffin granule fraction prepared from the bovine adrenal medulla and was released by high K+ and/or nicotine from cultured cells of the bovine adrenal medulla. Co-release of 7B2 with catecholamine induced by nicotine from the cultured bovine chromaffin cells was also observed. In an analysis of the bovine adrenal medulla chromaffin granule fraction on gel permeation chromatography, there was a major peak with an apparent molecular weight of 45,000, whereas a major peak with an apparent molecular weight of 20,000 was found in that on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. On reverse-phase HPLC, a major peak with a retention time of 35 min was observed in the bovine chromaffin granule fraction and in the bovine anterior pituitary extract. These findings indicate that 7B2 is a secretory protein in the bovine adrenal medulla. The possibility that 7B2 might be released with catecholamine, possibly in response to stress, warrants investigation.

Adrenal Medulla↗

Pharmacokinetics of doxorubicin, (2"R)-4'-O-tetrahydropyranyl-adriamycin and aclarubicin.

The following paragraphs summarize the properties of ADR, THP and ACR in terms of their pharmacokinetics. The blood level of anthracyclines shows a three-phase function of decline: alpha, beta and gamma phases. Compared with other classes of anticancer agents, the anthracyclines are characterized by an extremely short T1/2(alpha) and an extremely long T1/2(gamma). These characteristics reflect the facts that anthracyclines are rapidly transferred to the tissues and that they are retained for a long time in the body. In comparison with ADR, the T1/2(alpha) of THP is relatively short and T1/2(alpha, beta and gamma) of ACR are also short. Anthracyclines show large values for K12 and K13, transfer rate constants of the drug from the blood to the tissues, and small values for K21 and K31 transfer rate constants of the drug from the tissues to the blood. This means that these drugs are rapidly transferred to the tissues, from which they are then slowly released. The order of magnitude of K12 and K13 was THP greater than ACR greater than ADR. The order for K21 and K31 was ACR greater than THP greater than ADR. Anthracyclines are also characterized by small distribution volumes (V1) in the blood circulation, and very large distribution volumes (V2 and V3) in the tissue compartments. The order of magnitude for V2 and V3 was THP greater than ADR greater than ACR. Anthracyclines achieved high concentrations in such thoracic and abdominal organs such as lung, heart, thymus, liver, kidney, spleen and digestive tract. ADR showed the highest levels in liver and kidney, while THP and ACR showed their highest concentrations in lung and spleen. A decrease in the drug concentration in various organs is slow in the case of ADR, while rapid in the cases of THP and ACR. Most of the distributed drug is the unchanged form with ADR, whereas metabolites are common with ACR. THP is partially converted to ADR in liver. Anthracyclines were usually excreted over a long period of time at a high rate in the bile and at a low rate in the urine. Orally-administered ACR showed considerably good absorption from the digestive tract. The metabolism of anthracyclines was carried out in vivo and resulted in the formation of bioactive glycoside metabolites and inactive aglycone metabolites.(ABSTRACT TRUNCATED AT 400 WORDS)

Aclarubicin↗

[Pharmacokinetics and disposition of a new anticancer antibiotic (2''R)-4'-O-tetrahydropyranyladriamycin in rats. Distribution and excretion after a single administration].

Blood levels, tissue distribution and excretion of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) were studied in rats received 14C-THP or unlabeled THP at a dose of 5 mg/kg, respectively. The THP disappeared rapidly from the blood and transferred to tissues immediately after an administration. Pharmacokinetic analysis of the plasma level of THP by the simulation according to a three-compartment open model provided large values of apparent volume of distribution in the tissue compartment. The plasma half-lives of THP in alpha, beta and gamma-phases were 0.25 minute, 0.241 hour and 5.11 hours, respectively. The THP was distributed to the lung and spleen at a level about 100 times as high as the plasma level after an intravenous administration. A high level of THP was also found in the lymph node and gland tissues. Concentrations of THP in many tissues decreased to 1 microgram/g or less 24 or 72 hours after an injection of the drug, while the drug remained at higher levels in the thymus, spleen and tumor for a long time. After an injection of THP into the carotid artery, its distribution to the brain was apparent, but the level was lower after an injection to the tail vein. The amount of the drug transferred to a fetus was less than 0.2% of the dose. The major route for the excretion of THP after an intravenous administration was the fecal excretion via bile. Ratios of excretion of the radioactivity in the feces, urine and expired air were 80.3, 5.6 and 9.7% of the dose, respectively, 168 hours after an injection of 14C-THP. About 65% of the radioactivity was excreted in the bile up to 24 hours after injection but THP itself accounted for only 1/6 of the total radioactivity. About 80% of the excreted THP in the bile was in a conjugated form. Enterohepatic circulation of THP was observed mostly as metabolites or decomposed products of THP.

Animals↗

[Pharmacokinetics and disposition of a new antitumor antibiotic (2''R)-4'-O-tetrahydropyranyladriamycin in rats. Distribution and excretion after multiple administration].

The accumulation of (2''R)-4'-O-tetrahydropyranyladriamycin (THP) was studied in rats received intravenous administration of 14C-THP at a dose of 0.5 mg/kg/day for 14 consecutive days by determining blood and tissue levels and the excretion of the radioactivity. The radioactivity levels in plasma and blood cells after the multiple administration were higher than those after single administration. The half-life of the radioactivity after the multiple administration was longer in the blood cells but not in the plasma than the half-life after a single administration. Tissue levels of the radioactivity after the multiple injection were 2 to 4 times as high as the levels after a single injection except for the brain and testes in which a large accumulation of the radioactivity was observed. However, little accumulation of unlabeled THP was found in most tissues when determined by HPLC. The accumulation of radioactivity in tissues, therefore, was due to metabolites of THP. The disposition of 14C-THP was also examined in rats which had previously received unlabeled THP (0.5 mg/kg/day) for 13 days. The pretreatment did not affect the disposition of 14C-THP seriously, although the pretreatment raised tissue levels slightly and a rebound of plasma level of 14C-THP, and lowered the fecal excretion ratio. No induction of hepatic drug metabolizing enzymes was observed in rats after repeated administrations of THP for consecutive 14 days.

Aminopyrine N-Demethylase↗

Pharmacokinetics and disposition of (2''R)-4'-O-tetrahydropyranyladriamycin in dogs.

The pharmacokinetics and physiological disposition of a novel anthracyclines, (2''R)-4'-O-tetrahydropyranyladriamycin (THP) were studied in dogs by an HPLC analysis. The THP administered intravenously (1.5 mg/kg) disappeared rapidly from the plasma immediately after an injection of the drug. The plasma level of THP was lowered in a triphasic pattern up to 24 hours and was simulated by a three-compartment open model in which the half-lives of alpha-, beta- and gamma-phase were calculated to be 0.0116 hour, 0.152 hour and 7.02 hours, respectively. The blood cell level of THP was about 10 times as high as the plasma level during the observation. In the study of tissue distribution of THP 2 and 8 hours after the administration, the highest concentration of THP was found in the spleen and lung and these concentrations were diminished quickly. However, in the lymph nodes and bone marrow concentrations of THP increased with a lapse of time. THP and its metabolites were excreted in the bile by 2.7% of dose during 8 hours in the bile-cannulated dogs. Urinary recovery of THP and its metabolites was about 1.3% of the dose up to 72 hours. In these experiment, THP was metabolized to THP-OH and ADM, and to aglycones which were excreted in conjugated forms. The results obtained from a similar study on ADM were compared and discussed.

Animals↗

[Pharmacokinetic studies of THP-ADM (tetrahydropyranyl adriamycin)].

THP-ADM is a new antitumor agent which belongs to the anthracycline family. This agent has shown a high therapeutic index compared with the mother compound, Adriamycin, in preclinical and clinical studies. This time, a pharmacokinetic study of THP-ADM was performed and the following characteristics of this agent were clarified. Short t1/2 was noted compared with that of Adriamycin in a 3-compartment open model. Leukocyte concentration of THP-ADM was much higher than that of plasma or red blood cells. Renal excretion over 48 hours was 9% and biliary excretion over the same period was 20%. Tissue concentration revealed high THP-ADM and low Adriamycin in all tissues excluding the liver. In liver tissue, a high concentration of Adriamycin and a low concentration of THP-ADM was observed. A small amount of Adriamycin was noted in the plasma following THP-ADM administration. The Adriamycin was most likely related to the small amount of existing Adriamycin in THP-ADM or conversion of THP-ADM to Adriamycin in the liver tissue or both. Poor penetration of THP-ADM was noted into the third space.

Doxorubicin↗

Regional distribution of a novel pituitary protein (7B2) in the rat brain.

The regional distribution of a novel pituitary protein (7B2) in the rat brain was studied using a specific and sensitive radioimmunoassay. Immunoreactive (IR)-7B2 was distributed throughout the brain, with the highest concentrations in the pituitary, hypothalamus and basal ganglia. Immunoreactive 7B2 from the brain and other tissues had an apparent molecular weight of around 20,000 as estimated by SDS-polyacrylamide gel electrophoresis as observed with other tissues. In homozygous Brattleboro rats which do not synthesize vasopressin or its associated neurophysin, IR-7B2 levels in the brain and pituitary gland were shown to be similar to those of control animals. Furthermore, the molecular weight of 7B2 in the brain and pituitary gland of homozygous Brattleboro rats was similar to that of control animals.

Animals↗

Pharmacokinetics and disposition of 4'-O-tetrahydropyranyladriamycin in mice by HPLC analysis.

The plasma level of 4'-O-tetrahydropyranyladriamycin (THP) declined rapidly after IV injection to mice, with a t1/2(alpha) of 0.453 min. Only 1.2 micrograms/ml THP was detected 2 min after injection of 5 mg/kg. The drug was immediately transferred to various tissues, where the drug levels were much higher than the plasma concentration. In the lung and spleen, 8.26 and 13.6 micrograms/g THP was present, respectively, 2 h after administration. Major metabolites of THP were 13-dihydro-THP, ADM, 7-deoxyadriamycinone, and 7-deoxy-13-dihydro-adriamycinone. Only 1.12% of the dose had been recovered in the urine by 48 h after injection as THP and its metabolites, according to analysis by HPLC fluorospectroscopy. The observed disposition of THP was compared with that of adriamycin (ADM). The plasma disappearance and tissue transfer of THP were faster than those of ADM. THP levels in the spleen and lung were higher and those in the heart and liver were lower than the corresponding ADM levels. Drug levels declined more quickly in most tissues in the case of THP than of ADM. Tissue distributions after single bolus and multiple injections were also compared and discussed.

Animals↗