Biomedical subjects
S Fukuchi
Publications and source records attributed to S Fukuchi.
Effect of aging on endothelin-induced prostaglandin I2 release in isolated hind legs of the spontaneously hypertensive rat.
We evaluated the effect of aging on spontaneous release of prostaglandin I2 (PGI2; measured as 6-keto-PGF1a) as well as on endothelin-induced release of PGI2 from isolated hind legs perfused with Krebs-Ringer solution in 5-week-old, 10-week-old and 40-week-old Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). The spontaneous release of PGI2 was stable up to 40 minutes for both strains. The amount of the spontaneous release of PGI2 tended to fall with advancing age in WKY, while it remained unchanged in SHR. Porcine endothelin-1 (pET-1) added to the perfusion medium (2 x 10(-12)-2 x 10(-10) M) increased PGI2 release in a dose-dependent fashion in both strains regardless of age. However, the maximal increase of PGI2 release evoked by endothelin (2 x 10(-10) M) was significantly greater in 40-week-old SHR compared with age-matched WKY. These results not only suggest that there exists a much greater reservoir of vascular PGI2 synthesis in SHR, but also imply that the enhanced release of PGI2 in response to endothelin, the most potent vasoconstrictor known, may function as a factor or a modulator to attenuate endothelin-induced vasoconstriction in senescent SHR.
[Release of endothelin from isolated perfused human umbilical vein. I: Effect of ionomycin].
Endothelin-like immunoreactivity (ET-LI) was directly measured in the perfusate from the isolated human umbilical vein perfused with Krebs-Ringer solution. The identity of the immunoreactive peptide was confirmed as ET-1 by high-performance liquid chromatography. The rate of release of ET-LI was 86.7 +/- 25.9 (SE) fmol during the first perfusion period of 30 min, and it remained stable at least for 4 hours. Calcium ionophore ionomycin, added to the perfusion medium (10(-7)-10(-6) M), stimulated the ET-LI release in a dose-dependent fashion; it increased the rate of release by 29.1% and 143.4% over the control at the concentrations of 10(-7) and 10(-6) M, respectively. These results taken together with previous observations of synthesis of ET in cultured vascular endothelium provide direct evidence for local generation and subsequent release of ET from vascular beds of human beings.
[Fontan procedure for DORV with mitral atresia and anomalous hepatic vein connection to the left atrium--advantage of leaving right to left shunt in situ].
A 5-year-old boy with double outlet right ventricle, mitral atresia, pulmonary stenosis and anomalous hepatic vein drainage into left atrium underwent Fontan procedure leaving hepatic venous-left atrial connection. Systemic venous-left atrial connection provided enough filling volume of the systemic ventricle despite of high pulmonary resistance. Extra cardiac shunt between the systemic vein and left atrium would be the second best in fontan operation for cases with high pulmonary resistance.
A case of glomerulocystic kidney disease associated with hypothyroidism in man.
Glomerulocystic kidney (GCK), a rare disease mostly seen in infants and small children, is characterized by dilatation of Bowman's space. We report about a 32-year-old Japanese male with GCK. Although radiologic studies including computed tomography of the kidneys failed to show cysts in the corticomedullary regions, renal biopsy specimens revealed diffuse glomerular cystic lesions. Extrarenal malformations were not determined, but the patient was found to have hypothyroidism presumably due to a functional disorder of the hypothalamus (tertiary hypothyroidism). This is probably the fifth documented case of the disease in an adult. To our best knowledge, the association with hypothyroidism is rare. Although its pathogenic relevance to GCK is unknown, the endocrine dysfunction seems to have occurred as part of the extrarenal conditions of GCK, which calls further attention to this entity.
Effect of delapril hydrochloride on angiotensin II release from isolated rat hind legs.
The effect of the newly developed angiotensin-converting enzyme (ACE) inhibitor, delapril hydrochrolide (CV-3317), on the release of immunoreactive angiotensin II (irAng II) from isolated rat hind legs was compared with that of captopril. Both ACE inhibitors, added to the perfusion medium (2 X 10(-9) - 10(-6) M), suppressed irAng II release in a dose-dependent manner, but the inhibition was greater with delapril than with captopril. The results provide further support for the concept that vascular tissues produce Ang II and release it in a regulated fashion. The results also suggest a possible link between the antihypertensive mechanism of ACE inhibitors, including delapril, and the suppression of vascular Ang II release.
[The inhibitory effects of glycyrrhizin and glycyrrhetinic acid on the metabolism of cortisol and prednisolone--in vivo and in vitro studies].
This experiment was carried out to investigate the inhibitory effects of glycyrrhizin and its aglycon, glycyrrhetinic acid, on the metabolism of cortisol and prednisolone in vivo and in vitro. The effects of glycyrrhetinic acid on the metabolism of cortisol were examined in vitro using rat and bovine liver homogenate. Glycyrrhetinic acid inhibits both hepatic delta 4-5-reductase and 11 beta-hydroxysteroid dehydrogenase in a dose-dependent manner, resulting in the decrease of conversion of cortisol to cortisone, dihydrocortisol and tetrahydrocortisol in rats. The concentrations of glycyrrhetinic acid inducing 50% inhibition of rat liver delta 4-5-reductase and 11 beta-hydroxysteroid dehydrogenase were 2.5 x 10(-6) M and 8.5 x 10(-6) M, respectively. Glycyrrhetinic acid also inhibits bovine liver 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase in a dose-dependent manner, resulting in the decrease of conversion of cortisol to dihydrocortisol and prednisolone to 20-dihydroprednisolone. The concentrations of this drug inducing 50% inhibition of 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase were 8.2 x 10(-6) M and 6.5 x 10(-6) M, respectively. This is the first report which demonstrates the marked inhibitory effects of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase in vitro. The effects of glycyrrhizin on the rate of metabolism of cortisol as well as prednisolone were studied in 23 patients with or without adrenal insufficiency. Glycyrrhizin had no effect on diurnal rhythm of plasma cortisol in 7 control subjects with normal pituitary adrenal axis, whereas glycyrrhizin significantly increased the half-time (T 1/2) and area under the curve (AUC) for plasma cortisol in 4 patients with adrenocortical insufficiency taking oral cortisol. Glycyrrhizin also increased T 1/2 and AUC for plasma prednisolone in 12 patients taking an oral prednisolone for at least 3 months. These results indicate that the suppression of hepatic delta 4-5-reductase, 11 beta-hydroxysteroid dehydrogenase and 20-hydroxysteroid dehydrogenase by glycyrrhizin and glycyrrhetinic acid may delay the clearance of cortisol and prednisolone and prolong the biological half-life of cortisol or prednisolone.
[The significance of cGMP and dopamine receptor on the natriuretic and hypotensive activities of synthetic atrial natriuretic polypeptide in essential hypertension].
This study was undertaken to clarify the role of dopamine receptor (DA2) on the effects of atrial natriuretic polypeptide(ANP) on blood pressure, plasma and urinary cyclic GMP, and urinary sodium excretion, alpha-human ANP (alpha-hANP) was intravenously administrated to 7 normal subjects and 14 patients with essential hypertension as follows: first a dose of 0.01 micrograms/kg/min for 30 minutes, and then 0.03 micrograms/kg/min with or without metoclopramide(MC) for 30 minutes. After the infusion of the 0.03 micrograms/kg/min dose of alpha-hANP, systolic blood pressure fell from 115 +/- 17 mmHg to 109 +/- 15 mmHg in normal subjects, and fell significantly from 163 +/- 33 mmHg to 145 +/- 26 mmHg in patients with essential hypertension. Diastolic blood pressure fell from 101 +/- 14 mmHg to 92 +/- 7 mmHg in patients with essential hypertension but did not change in normal subjects. A dose of 0.03 micrograms/kg/min of alpha-hANP led to a threefold rise in urine volume and twofold rise in urinary sodium excretion in normal subjects, and a fivefold rise in urine volume and fourfold rise in urinary sodium excretion in patients with essential hypertension. However, there was no relationship between the hypotensive and natriuretic effects of alpha-hANP in either normal subjects or patients with essential hypertensions. The infusion of a 0.03 micrograms/kg/min dose of alpha-hANP increased plasma cyclic GMP concentration from 4.1 +/- 2.1 pmol/ml to 34.3 +/- 25.Opmol/ml in normal subjects and from 4.5 +/- 2.6 pmol/ml to 20.3 +/- 7.4 pmol/ml in patients with essential hypertension. The rise in plasma cyclic GMP by alpha-hANP was suppressed by MC both in normal subjects and patients with essential hypertension. Urinary cyclic GMP excretion also increased during the infusion of alpha-hANP, but this effect was not suppressed by MC. Furthermore, plasma aldosterone concentration (PAC), which was depressed by alpha-hANP in normal subjects and patients with essential hypertension, was increased by MC. These results suggest that the hypotensive effect of alpha-hANP may depend not only on the natriuretic effect, but also on vasodilatation, the inhibition of aldosterone production or the suppression of the sympathoadrenomedullary system. Cyclic GMP may be produced through the DA2 receptor in vascular tissue but not in the kidney.
Ventricular volume characteristics in double-inlet left ventricle before and after septation.
Septation is one of the surgical choices for double-inlet left ventricle, yet postoperative hemodynamics have not been well defined. We studied ventricular volume characteristics in 10 patients with double-inlet left ventricle before and after septation. Preoperative end-diastolic volume (EDV) of the ventricle was 291 +/- 111% (+/- SD) of normal and ejection fraction (EF) was 0.59 +/- 0.07. Postoperatively, EDV of the right-sided ventricle (RV) was 82 +/- 24%, and EDV of the left-sided ventricle (LV) was 153 +/- 41%. Ejection fraction of the RV was 0.77 +/- 0.10, and LVEF was 0.49 +/- 0.13. On the short-axis view of two-dimensional echocardiography, fractional change of the cross-sectional area was 0.65 +/- 0.16 for the RV and 0.23 +/- 0.11 for the LV. Fractional shortening of the septum-to-ventricular free wall axis was 0.51 +/- 0.17 in the RV and -0.05 +/- 0.09 in the LV. Analysis of the curvature of the new septum during cardiac cycle on two-dimensional echocardiography revealed that the septum shifted to the right side during systole in all patients in whom the systolic LV/RV pressure ratio was larger than 1.0. The septum shifted toward the LV during diastole in eight patients in whom end-diastolic pressure in the RV was higher than or equal to that in the LV, whereas it remained in the right side in two patients with higher left-side pressure. The cardiac index of these two patients was 2.4 and 2.6 l/min/m2, respectively, whereas it averaged 4.4 +/- 1.0 l/min/m2 in the other eight patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Re-evaluation of the plasma renin-angiotensin system in anephric patients.
In view of recent observations that a number of extrarenal tissues have the potential to produce angiotensin II and release it in a regulated fashion, we made measurements of immunoreactive angiotensin I (irAng I) and angiotensin II (irAng II), along with active and inactive renin, and angiotensinogen in plasma of seven anephric patients and of 16 normal healthy volunteers to gain insight into possible sources of plasma Ang II. High performance liquid chromatography clearly demonstrated that the predominant component of irAng II in anephric plasma is the biologically active octapeptide Ang II. Plasma renin activity (PRA), and active and inactive renin all were detected in all of the anephrics but their levels were decreased to 33% for PRA, 12% for active renin, and 18% for inactive renin when compared with those in healthy subjects. While plasma angiotensinogen was significantly but only slightly increased in anephric patients (+28% over the mean value for normal subjects), irAng I and irAng II both were present in quantities almost comparable with those in normals. These results suggest that local angiotensin production contributes, in part at least, to the circulating plasma Ang II. Vascular tissue seems to be the best candidate responsible for such a mechanism, on the basis of recent demonstrations of unequivocal, regulated release of Ang II from diverse vascular beds.
[Pulmonary artery banding for double inlet left ventricle].
Thirteen patients with double-inlet left ventricle who had undergone pulmonary artery banding (PAB) were reviewed. At the time of PAB, the age ranged from 2 months to 3 years. Pulmonary-systemic arterial pressure ratio and pulmonary arterial mean pressure were reduced from 0.95 +/- 0.12 to 0.4 +/- 0.18, and from 57.3 +/- 11.6 mmHg to 29.9 +/- 12.7 mmHg after PAB. Pulmonary resistance showed no statistically significant change after PAB. (from 7.6 +/- 5.2 unit to 4.8 +/- 3.9 unit) Ventricular end-diastolic volume decreased from 379.9% +/- 140.0% to 275.7% +/- 118.0% after PAB. The smallest one was 170% who successfully underwent septation procedure. Ejection fraction significantly decreased from 64.5 +/- 6.1% to 56.3 +/- 7.9%. (p less than 0.005) Ventricular end-diastolic pressure showed no significant change after PAB. (from 9.2 +/- 2.8 mmHg to 9.9 +/- 2.0 mmHg) After PAB subaortic stenosis occurred in three cases and pressure gradient were 10, 20, and 85 mmHg, respectively. Seven cases, including three cases with subaortic stenosis, underwent septation procedure and all survived. Before septation, ventricular end-diastolic volume calculated as % of normal left ventricular volume ranged from 173% to 570% and pulmonary resistance ranged from 1.6 unit to 11 unit. These data suggested that the patients with double-inlet left ventricle had efficient ventricular volume and cardiac function for septation even after PAB.
[Studies on immunoreactive somatostatin and gastrin contents of the gastric mucosa in patients with duodenal ulcer--comparison to patients with fundic gland polyposis and normal subjects].
The immunoreactive gastrin (IRG) and somatostatin (IRS) contents in gastric mucosa were measured from the same biopsy specimen of the same patients with duodenal ulcer (DU) at the active stage and healing stage, and compared to those of patients with fundic gland polyposis (FP) and endoscopically normal subjects whose gastric mucosa had only slight atrophic change (Control). The IRS in both the antrum and the gastric body of DU were significantly lower than those of the other two groups, and those showed no difference between the two stages. In all groups, there was a significant positive relation between the IRG and IRS in the antrum. In DU, particularly at the active stage, the relative decrease of the IRS against the IRG was prominent compared to the other two groups. In FP, which has similar background gastric mucosa and ability of acid output to those of DU, it was found that somatostatin was secreted sufficient to control gastrin secretion and acid output. Whereas in DU, secretion of somatostatin was reduced and, particularly at the active stage, it was considered that somatostatin, which could control increased gastrin secretion and increased acid output, was not secreted.
[Clinical significance of evaluation of lipid peroxides in diabetes mellitus].
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Low-dose endothelin stimulates release of prostaglandin I2 from isolated perfused hind legs in the rat.
A direct measurement of 6-keto-prostaglandin F1a (6-keto-PGF1a), a stable metabolite of prostaglandin I2, was made in the perfusate from isolated rat hind legs perfused with Krebs-Ringer solution. The rate of release of 6-keto-PGF1a was 5.28 +/- 0.24 ng during the first perfusion period of two min, and it remained stable at least for 40 min. The biological integrity of the preparation was confirmed by inhibition (52%) of 6-keto-PGF1a release by indomethacin (5 X 10(-5) M) in the perfusion medium. Low-dose infusion (5, 10, and 20 pM, for 10 min each) of endothelin (ET) elicited small but significant increment in the release of 6-keto-PGF1a in a dose-dependent fashion; the maximal per cent increase of 6-keto-PGF1a release evoked by ET (20 pM) was approximately +40% over the basal rate. These results taken together with the previous observations of synthesis of ET in the vascular tissue suggest an intriguing relationship between vasoconstrictive ET and vasodilatory prostaglandins in the local control of vascular tone.
[Konno procedure for congenital aortic valve stenosis with pulmonary valve stenosis].
Although aortic and pulmonary valve stenosis are among the most common congenital heart defects, the combination of both aortic and pulmonary valve stenosis in the same patient appears to be very uncommon. Accurate diagnosis of combined valvular stenosis is imperative prior to surgical correction, otherwise surgery of one of the lesions may result in an insufficient hemodynamic improvement. A seven-year-old girl with congenital aortic and pulmonary valve stenosis associated with hypoplastic aortic annulus underwent Konno's operation, pulmonary valvotomy and resection of anomalous muscle of the right ventricular outflow tract simultaneously. The operation was successfully performed and postoperative course was uneventful.
Septation and Fontan repair of univentricular atrioventricular connection.
From April 1986 to September 1988, 12 patients with double- or common-inlet left ventricle and left anterior rudimentary right ventricle underwent septation while 17 patients with double- or common-inlet left or right ventricle underwent the Fontan operation. In the septation group, three patients who had pressure gradients ranging from 10 to 85 mm Hg between the left ventricle and the aorta underwent enlargement of the outlet foramen, and all survived. One of the 12 patients had a common atrioventricular valve that was repaired by separating the atrioventricular valve by the procedure used for atrioventricular septal defect. One had complete heart block before septation and the other one had it after separation. One 17-year-old woman, who had the smallest left ventricle (168% of normal), died in the hospital (mortality, 8.3%). In the Fontan group, one patient who died in the hospital (5.9%) had high pulmonary resistance of 4.4 U/m2, and one late death (5.9%) occurred in a patient who had complete heart block and a high mean pulmonary arterial pressure of 20 mm Hg. Because of suprasystemic pressure in the pulmonary ventricle, two patients had immediate takedown of the septation repair and substitution of the Fontan repair. Although right atrial pressure was almost equal in both groups after operation, the cardiac index was significantly higher in the septation group than in the Fontan repair group (p less than 0.01). These data suggest that patients who are candidates for either septation or Fontan repair might fare better with septation.
[Combined injection method by para and intra-variceal injection. Instrument and practice of technique].
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[Significance of tetrazolium salt based colorimetric assay (MTT assay) for isolated rabbit parietal cell].
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