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Biomedical subjects

S Usuki

Publications and source records attributed to S Usuki.

At least 91 records · Page 5Linked to original sources
PubMed1988

Metabolism of diltiazem. II. Metabolic profile in rat, dog and man.

The metabolism of diltiazem was studied in male rats and dogs after intravenous administration of 14C-diltiazem.HCl or in men after oral administration of a tablet of diltiazem.HCl. The main metabolites in rat urine, in decreasing order of content, were A4, M6, M4 and M5. The unchanged drug in the urine accounted for only 0.7% of the administered drug based on radioactivity. About 81% of biliary radioactivity in rat was due to water-soluble metabolites and the remainder was mostly acidic metabolites such as A4 and A6. In dog urine, the unchanged drug was most abundant (30.6% of the radioactivity in the 6-h urine), followed by A2, A1 and M2. The main metabolites of diltiazem in rat plasma were A2 and A4, while in dog plasma, the unchanged drug and A2 were found as main components. In human urine, M4, the unchanged drug, A2, MB, MD and M2 were the major components. Acidic metabolites, A1-A4, were found also in human plasma and A2 was the main metabolite found. These results indicated that the main metabolic pathway of diltiazem was an oxidative deamination which is extensive in the rat. Other metabolic pathways recognized in this study were oxidative demethylation, deacetylation, hydroxylation of the aromatic ring and conjugation. Although direct comparison may not be appropriate because of the different routes of administration, the metabolism of diltiazem in man appears to be more similar to that in the dog than that in the rat.

Administration, Oral↗
PubMed1988

Activity of deoxyribonucleic acid polymerase alpha stimulated by estrogen in the endometrium of the human uterus during the menstrual cycle.

To provide some insight into how deoxyribonucleic acid (DNA) synthesis occurs in the endometrium of the human uterus during the menstrual cycle, the DNA polymerase activities (alpha and beta) in endometrial samples taken from normal cycling women, and the concentration of estradiol-17 beta (E2) and progesterone in the serum were measured. DNA polymerase alpha activity increased gradually from the beginning of the menstrual cycle, reaching a peak 2-3 days before ovulation, and then showed a decrease. Increase in this activity occurred in parallel with that of the concentration of E2, but not progesterone, in the serum sample in the proliferative phase (correlation coefficient r = 0.924, p less than 0.001). In contrast, DNA polymerase alpha activity stimulated by estrogen in the endometrium of the 2nd grade amenorrheal women decreased abruptly after an injection of 125 mg progesterone. DNA polymerase beta activity showed no significant change during the menstrual cycle or after estrogen and progesterone treatment. These results suggest that estrogen seems to stimulate the induction of DNA polymerase alpha activity during cell proliferation in the endometrium of the human uterus.

Adult↗
PubMed1988

Follicle-stimulating hormone induces deoxyribonucleic acid polymerase alpha before deoxyribonucleic acid synthesis in immature rat ovarian follicles perfused in vitro.

To examine the effects of follicle-stimulating hormone (FSH) on cell proliferation and cell division in ovaries, deoxyribonucleic acid (DNA) polymerase activities and DNA concentrations were determined in ovarian follicles of immature, hypophysectomized, estradiol-treated rats perfused in vitro. Ovine FSH (2-20 micrograms/mL) significantly enhanced the DNA polymerase alpha activity in the follicles perfused for 180-300 minutes, whereas the DNA polymerase beta activity and DNA concentration showed no significant changes. It is concluded that FSH causes the induction of DNA polymerase alpha before DNA synthesis during follicle growth in immature rat ovaries.

Animals↗
PubMed1988

[Comparison of regional contractile dynamics and pathological findings of the left ventricular wall in patients with hypertrophic cardiomyopathy].

To investigate the relationship between regional contractile dynamics and regional myocardial lesions of the left ventricular wall in patients with hypertrophic cardiomyopathy (HCM), autopsy findings of 11 patients were compared with their ante mortem echocardiographic findings. The regional systolic wall thickenings (%RWT) of the interventricular septum (IVS) and left ventricular posterior wall (LVPW) obtained using M-mode echocardiography were converted into % normalized RWT (%NRWT) by the averaged %RWT in 15 normal subjects. The %NRWT was compared with the wall thickness obtained by echocardiography and/or autopsy, and histological findings, such as the myocardial fibrosis ratio, disarray area ratio, and mean myocyte diameter. 1. There were no significant correlations among wall thickness of the left ventricle, the myocardial fibrosis ratio, the disarray area ratio, and the mean myocyte diameter of each segment. 2. The %NRWT in 22 segments of the 11 patients with HCM was not significantly related to the echocardiographic wall thickness at end-systole, the autopsy wall thickness, the mean myocyte diameter and the disarray area ratio, but that correlated significantly with the echocardiographically-determined wall thickness at end-diastole (r = -0.53, p less than 0.02), and with the myocardial fibrosis ratios (r = -0.59, p less than 0.005). 3. The %NRWT in the IVS was significantly less than that in the LVPW. The %NRWT in all segments of the LVPW was significantly related to the myocardial fibrosis ratios (r = -0.80, p less than 0.005), but was not related to the wall thicknesses or the disarray area ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Prognosis of hypertrophic cardiomyopathy: echocardiographic and postmortem histopathologic study of 30 patients].

To clarify the influence of cardiac function of myocardial histologic lesions on the prognosis of hypertrophic cardiomyopathy (HCM), most recent echocardiographic findings of 30 deceased patients were reviewed. In 12 patients, histological sections from the left ventricular transverse plane made at necropsy were examined. According to the main causes of death, patients were categorized into four groups as sudden death (17 cases), heart failure death (four cases), embolic death (four cases), and non-cardiac death (five cases). 1. Clinically, atrial fibrillation and heart failure (NYHA III, IV) were frequently observed in heart failure and embolic groups. 2. Echocardiographically, left ventricular wall thickness did not differ among the four groups, but percent fractional shortening was significantly smaller in heart failure group than in non-cardiac group, and left ventricular end-diastolic dimension (LVDd) and left atrial dimension were significantly greater in heart failure group than in non-cardiac group. The normalized rapid filling rate was less in heart failure, embolic, sudden death and non-cardiac groups in that order. 3. Histopathologically, the mean myocyte diameter (MD) and percent area of disarray (%D) did not differ among the four groups, but % area of massive fibrosis (MF) greater than 2 mm2 was larger in heart failure, embolic, sudden death and non-cardiac groups in that order, especially in heart failure group. 4. Comparison of echocardiographic and histopathological findings: Though MD and %D did not correlate with any echocardiographic indices, %MF correlated significantly with LVDd (r = 0.83, p less than 0.005), and correlated inversely with the normalized rapid filling rate (r = -0.80, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Ovarian renin gene expression is regulated by follicle-stimulating hormone.

The regulation of renin and renin messenger RNA (mRNA) in the rat ovary was examined to test the hypothesis that the expression of renin gene and the secretion of renin in the ovary is the estrogen-mediated process that responds to follicle-stimulating hormone (FSH). In the ovary of the immature 25-day female rats, the concentration of renin mRNA was comparatively low, but 36 h after injection of FSH, the renin mRNA content showed a three-fold increase compared to the basal level. This increase was consistent with the stimulation of the total renin concentration in the ovary. On the other hand, the total renin concentration in the rat uterus gradually decreased, suggesting that the enhancement of the contents of renin and renin mRNA by FSH is an ovary-specific phenomenon. In hypophysectomized rats, the total renin concentration in the rat ovary was stimulated by the estrogen as well as FSH. These findings suggest that the production of ovarian renin is regulated by the pituitary hormone, particularly FSH.

Animals↗
PubMed1987

Identification of renin and renin messenger RNA sequence in rat ovary and uterus.

An increase in plasma prorenin during pregnancy suggests that prorenin might be synthesized in the ovary and the secretion of renin or prorenin may be stimulated by an ovarian steroid-mediated process. Recently, renin and angiotensinogen have been identified in human ovarian follicular fluid. However, there is considerable controversy over whether renin is synthesized in the ovary or derived from circulation. In the present study, we confirmed the presence of renin and renin mRNA in rat ovary and uterus by Northern blot analysis with rat renin cRNA as a hybridization probe. Our data show that ovarian or uterine renin is synthesized in the same cells. This suggests that the function of renin might be closely linked to the reproductive process.

Animals↗
PubMed1987

Effects of hachimijiogan, tokishakuyakusan and keishibukuryogan on the corpus luteum function and weights of various organs in vivo.

27-day-old female rats received 20 IU PMS and 56 hours later, 40 IU hCG and were orally given with 20 or 200 micrograms of Hachimijiogan (TJ-7), Tokishakuyakusan (TJ-23) or Keishibukuryogan (TJ-25) daily for 3 or 5 days before sacrifice. Seven days after hCG treatment, the serum and ovarian tissue were assayed for progestins. 200 micrograms/day of TJ-23 significantly (p less than 0.05) decreased the progesterone and 17 alpha-hydroxyprogesterone levels, whereas it significantly (p less than 0.01) increased 20 alpha-hydroxyprogesterone. TJ-7 and TJ-25 showed a tendency to decrease these progestins. These results suggest that TJ-23 has a luteolytic effect on the corpus luteum in vivo.

Animals↗
PubMed1987

Effects of hachimijiogan, tokishakuyakusan and keishibukuryogan on progesterone secretions by corpus luteum.

27-day-old rats received 20 IU of PMS subcutaneously, and 56 hours later, 40 IU of hCG to induce superovulated ovaries. Seven days after the hCG treatment, the ovaries were resected and incubated or perifused with an extract of Hachimijiogan (TJ-7), Tokishakuyakusan (TJ-23) or Keishibukuryogan (TJ-25). Progesterone in media was assayed by radioimmunoassay. In the incubation study, TJ-23 significantly (p less than 0.001, p less than 0.05) increased progesterone concentrations, while TJ-7 or TJ-25 showed no remarkable effect. In the perifusion study, TJ-23 or TJ-25 augmented progesterone levels, whereas TJ-7 revealed no effect. These results suggest that TJ-23 or TJ-25 stimulates the corpus luteum to secrete progesterone.

Animals↗
PubMed1987

Metabolic fate of diltiazem. Distribution, excretion and protein binding in rat and dog.

Pharmacokinetics of (+)-(2S,3S)-2,3-dihydro-3-acetoxy-2-(4-methoxyphenyl)-5- [2-(dimethylamino)ethyl]-1,5-benzothiazepin-4(5H)-one hydrochloride (diltiazem-HCl, Cardizem, Herbesser) in rats and dogs were investigated using 14C-diltiazem-HCL. The plasma concentration of unchanged drug in rats was 1.78 microgram/ml 1 min after intravenous administration at a dose of 3 mg/kg, and rapidly decreased thereafter with a half-life of 20 min (alpha-phase) and 56 min (beta-phase). In contrast, the plasma concentration of radioactivity in rats increased during 0-2 h in spite of intravenous administration, and thereafter the level of radioactivity in plasma decreased very slow. In dogs, the plasma concentration of unchanged drug was 0.138 micrograms/ml 1 min after intravenous administration at a dose of 0.2 mg/kg, and then decreased with a half-life of 2.5 min (alpha-phase) and 1.68 h (beta-phase). Dog plasma level of radioactivity decreased once after intravenous administration, but increased from 30 min to 1 h. Unchanged drug plasma levels at 1 h after intravenous administration were 6.6 and 35.1% of the plasma radioactivities in rats and dogs, respectively. When 14C-diltiazem-HCl was orally administered, unchanged drug plasma levels in rats and dogs were 1.8 and 12.8% of the plasma radioactivities at 15 min, respectively. Therefore, the first-pass effect was extensive, especially in rats. Rat whole body autoradiograms showed that radioactivity distributed well to tissues and organs in either route of administration. Similar results were obtained by the method of counting the radioactivity in the tissues and organs of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Relationships between segmental left ventricular wall motion abnormalities and pathological findings in patients with dilated cardiomyopathy].

Relationships between segmental left ventricular wall motion abnormalities and myocardial fibrosis at autopsy were examined in 12 patients who died of dilated cardiomyopathy. In each case, wall motion abnormalities were assessed by two-dimensional echocardiograms for 11 segments, and semiquantitatively evaluated as normokinesis (N) to hypokinesis (H), severe hypokinesis (SH) or akinesis (A). From the necropsy specimens, the myocardial fibrosis ratio was histologically quantitated using a point-counting method in each segment corresponding to the echocardiographic segment. Wall motion abnormalities and the fibrosis ratio correlated significantly in a total of 132 segments of the 12 patients, but there were some discordances. The cases were then categorized in uniform and non-uniform groups based on the patterns of myocardial fibrosis. Wall motion abnormalities correlated much better with the fibrosis ratio in a total of 44 segments among four cases with non-uniform fibrosis, whereas no significant correlation was found in a total of 88 segments in eight cases with uniform fibrosis. The latter group had more severe segmental wall motion abnormalities in the interventricular septum than in the left ventricular free wall; and in the apical portion rather than in the basal portion, although no significant difference was observed in the fibrosis ratio among these regions. Patients with non-uniform fibrosis had higher incidences of chest pain and sudden deaths and a significantly larger left ventricular end-diastolic dimension on M-mode echocardiogram as compared to those with uniform fibrosis. Pathologically, in the former group, the heart was heavier, the mean left ventricular fibrosis ratio was significantly higher, and there was a greater incidence of infiltration of the myocardium by mononuclear cells, but there was no difference in the mean left ventricular wall thickness. These results suggest that myocardial fibrosis mainly contributes to the wall motion abnormalities in cases with non-uniform fibrosis which may be caused by chronic myocarditis, but not in cases with uniform fibrosis. In the latter group, other factors such as reduced contractility of the myocardial cells or lack of a compensatory mechanism for wall stress seem to play important roles in causing left ventricular wall motion abnormalities.

Adult↗
PubMed1986

Follicle-stimulating hormone and estrogen elevate deoxyribonucleic acid alpha-nucleotidyltransferase activity in relationship to deoxyribonucleic acid synthesis in immature rat ovaries.

The deoxyribonucleic acid polymerase activities and deoxyribonucleic acid contents of ovaries were measured to clarify the relationship between hormone-stimulated cell proliferation and the enzymes in ovaries of immature intact rats (4 to 29 days after birth) and hypophysectomized rats. The specific activity of deoxyribonucleic acid alpha-nucleotidyltransferase (the activity per microgram of deoxyribonucleic acid of the ovaries) drastically increased with an increase in the deoxyribonucleic acid content of the ovaries from 4 to 14 days after birth and then remained constant or slightly decreased after the increase, while the activity decreased gradually after hypophysectomy with no increase in the DNA content. Ovine follicle-stimulating hormone or estradiol-17 beta enhanced the deoxyribonucleic acid synthesis and alpha-nucleotidyltransferase activity in the ovaries of hypophysectomized rats, while deoxyribonucleic acid beta-nucleotidyltransferase activity showed no significant change. Ovine luteinizing hormone, progesterone, and testosterone caused no significant increases. These results suggest that follicle-stimulating hormone or estrogen causes the induction of deoxyribonucleic acid alpha-nucleotidyltransferase accompanied by deoxyribonucleic acid synthesis in cell proliferation in immature rat ovaries.

Animals↗
PubMed1986

Specific tritium labeling of glucosyl- and galactosylceramides at the 6-position of the carbohydrate moiety using CrO3-graphite.

A new procedure for introducing tritium into the carbohydrate portions of glucosyl- and galactosylceramides was developed using a new catalyst, CrO3-graphite, which specifically oxidizes the primary alcohol group to the aldehyde. About 10% of the glycolipid was converted to the aldehyde and the aldehyde produced was then reduced back to the original form with KB3H4. After methanolysis, more than 96.7% of the radioactivities of [3H]glucosyl- and [3H]galactosylceramides were found to be located in the carbohydrate portions, and the specific activities of the [3H]galactosyl- and [3H]glucosylceramides were 2.08 to 4.30 X 10(4) cpm/nmol, which could be increased greatly by purifying the aldehydes and reducing them with KB3H4. In addition, beta-galactosidase activity was successfully determined with [3H]galactosylceramide as the enzyme substrate; the Km was 18.73 mM and the Vmax was 11.63 nmol/mg/h, indicating that no significant structural modification occurs during the oxidation.

Animals↗
PubMed1986

Hachimijiogan changes serum hormonal circumstance and improves spermatogenesis in oligozoospermic men.

28 men with oligozoospermia and 7 with azoospermia received 7.5 g of Hachimijiogan, daily for 8 to 28 weeks. Examinations of semen in oligozoospermic men after treatment revealed a remarkable increase in number (78%) and moderate increase in sperm motility (53%) and in volume (56%), and fertility index was also remarkably improved, whereas no improvement was found in azoospermic men. Furthermore, serum estradiol-17 beta level was significantly increased (P less than 0.005) after treatment, while LH, FSH, prolactin and testosterone levels in sera showed no significant change. These results suggest that Hachimijiogan increases serum estradiol-17 beta levels and improves spermatogenesis in oligozoospermic men.

Estradiol↗
PubMed1986

Effects of hachimijiogan, tokishakuyakusan and keishibukuryogan on estrogen and progesterone secretions by rat preovulatory follicles.

Ovaries of rats 48 hours after injection of 10 IU PMS when 27 days old were incubated or perifused with NIH-LH, Hachimijiogan (TJ-7), Tokishakuyakusan (TJ-23) and Keishibukuryogan (TJ-25). TJ-7, TJ-23 and TJ-25 decreased estradiol-17 beta (E2) levels in media and LH effects on progesterone secretions, while they increased progesterone in media and LH effects on E2 secretions. These results suggest that TJ-7, TJ-23 or TJ-25 stimulates preovulatory follicles to secrete progesterone but to suppress E2 secretions. Furthermore, it is indicated that their combination treatment with LH multiplies the sole effect of LH on E2 secretions but suppresses LH effects on progesterone.

Animals↗
PubMed1986

Increase in DNA polymerase alpha activity associated with DNA synthesis due to FSH or oestrogen in ovaries of immature rats.

DNA polymerase activities and DNA content of ovaries from immature intact rats (4-29 days after birth), hypophysectomized rats and hormone-treated hypophysectomized rats were measured. During normal ovarian growth DNA polymerase alpha activity and DNA content of ovaries increased. The polymerase activity decreased gradually after hypophysectomy without any alteration in the DNA content. Administration of ovine FSH (2 micrograms/day) or oestradiol-17 beta (1 mg/day) to hypophysectomized rats enhanced ovarian DNA content and DNA polymerase alpha activity, whereas DNA polymerase beta activity did not change significantly. These results suggest that DNA polymerase alpha participates in DNA synthesis in these ovaries. The specific activity of DNA polymerase alpha (the activity per microgram DNA) in the ovaries increased between 4 and 14 days after birth, and then remained almost constant; the specific activity declined gradually after hypophysectomy. Administration of FSH or oestradiol-17 beta but not of ovine LH, progesterone or testosterone to hypophysectomized rats restored the specific activity. Mixing experiments with different kinds of ovarian extracts suggested that no activators of DNA polymerase alpha were present in the extracts. These results suggest that FSH or oestrogen causes the induction of DNA polymerase alpha accompanied by DNA synthesis during cell proliferation in ovaries of immature rats.

Animals↗