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Biomedical subjects

S Fukuchi

Publications and source records attributed to S Fukuchi.

At least 73 records · Page 4Linked to original sources

Tuberculous peritonitis with extraordinarily high serum CA125.

A 74-year-old woman who was admitted for the evaluation of ascites showed a marked elevation of serum CA125 level. Laparoscopy revealed the presence of numerous white modules (approximately 5 mm diameter) on the peritoneum suggestive of tuberculomas. A biopsy specimen showed epithelioid cells and Langhans-type giant cells. Following the administration of diuretics, the level of serum CA125 decreased concomitantly with the decrease in the volume of peritoneal fluid. The level of CA125 decreased further with the administration of antituberculosis agents. Clinical specimens were negative for mycobacteria. We conclude that the elevated serum level of CA125 was due to peritoneal tuberculosis and consequent ascites. Thus, tuberculous peritonitis should be considered in the presence of an unexplained, abnormally elevated serum level of CA125.

Aged↗

Palliative repair of aortic atresia associated with tricuspid atresia and transposition of the great arteries.

Successful palliative repair of aortic atresia and hypoplastic aortic arch associated with tricuspid atresia in a neonate is described. The repair consisted of reconstruction of the hypoplastic aortic arch with an equine pericardial patch, division of the patient ductus arteriosus, connection of the pulmonary artery to the aorta, implantation of the proximal part of the ascending aorta into the main pulmonary artery, and anastomosis of a polytetrafluoroethylene graft 5 mm in diameter between the right ventricular outflow tract and the central pulmonary artery, which was transferred anteriorly to the main pulmonary artery.

Abnormalities, Multiple↗

The antihypertensive mechanism of delapril, a newly developed converting enzyme inhibitor, is related to the suppression of vascular angiotensin II release in the spontaneously hypertensive rat.

Accumulating evidence suggests an important role of vascular renin-angiotensin system (RAS) in the local control of arterial tone. To further gain insight into the significance of vascular RAS in hypertension, we investigated the relationship between the antihypertensive action of delapril, a newly developed converting enzyme inhibitor (CEI), and its effects on vascular angiotensin II (Ang II) release in spontaneously hypertensive rats (SHR). Male SHRs were given delapril or its active metabolite (5-hydroxydelapril diacid; 5-hydroxy-DPD) orally (10 mg/kg/day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was directly determined by extraction with Sep-Pak C18 cartridges connected to the perfusion system. Both delapril and 5-hydroxy-DPD produced a sustained antihypertensive action. The spontaneous release of Ang II from isolated perfused hind legs of control SHRs was about 50 to 110 pg during the first 30 min of perfusion, and it remained stable up to 3 h. Another active metabolite, delapril diacid (DPD), when added to the perfusion medium (10(-9) to 5 x 10(-5) mol/L), suppressed the Ang II release in a dose-dependent manner. The maximal percent inhibition of Ang II released evoked by DPD (5 x 10(-6) mol/L) was approximately 51%. Oral pretreatment of either delapril or 5-hydroxy-DPD for 2 weeks suppressed the Ang II release by 61% and 73% for delapril and 5-hydroxy-DPD, respectively. These results suggest the presence of a functional RAS in vascular tissues, and that delapril exerts its antihypertensive effect through inhibition of vascular Ang II release in SHRs.

Administration, Oral↗

Effect of delapril on the vascular angiotensin II release in isolated hind legs of the spontaneously hypertensive rat: evidence for potential relevance of vascular angiotensin II to the maintenance of hypertension.

1. In view of a recent interesting hypothesis that the vascular renin-angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar-Kyoto strain (WKY). 2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep-Pak C18 cartridges connected to the perfusion system. 3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9 +/- 17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5 +/- 9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose-dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR. 4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.

Angiotensin II↗

Distinct localization of renin and angiotensins in separate subcellular fractions of the rat adrenal cortex.

The subcellular localization of renin and immunoreactive angiotensins I and II was studied in rat adrenal cortical tissues. The identity of the immunoreactive angiotensins was confirmed as angiotensin I and angiotensin II by radioimmunoassay and high-performance liquid chromatography, respectively, with reference to standard compounds. By differential centrifugation of tissue homogenate in 0.25 M sucrose/30 mM Tris-HCl/l mM EDTA, pH 7.4, specific immunoreactive renin was found to be localized principally (60%) in the mitochondrial fraction (P2), whereas about 40% of both angiotensins I and II was contained in the soluble fraction; only 18-20% of both peptides was contained in the P2 fraction. On Percoll density gradient centrifugation of P2, renin was fractionated mostly in a denser band whereas angiotensins I and II were contained in a lighter density area closely corresponding to mitochondrial and lysosomal marker enzymes. These results suggest that renin and angiotensins in the cells of the rat adrenal gland reside in different subcellular compartments and argue against intracellular formation of angiotensins by renin in renin granules.

Adrenal Cortex↗

Exaggerated response to electrical nerve stimulation of angiotensin II release in isolated perfused hind legs of spontaneously hypertensive rats.

Previously we reported that a large amount of immunoreactive angiotensin II (Ang II) was released from isolated perfused rat hind legs at steady rates for several hours. In view of a recent intriguing hypothesis that the vascular renin-angiotensin system plays an important role in the maintenance of high blood pressure in certain forms of experimental hypertensive models, the release of immunoreactive Ang II from isolated hind legs of spontaneously hypertensive rats (SHR) was examined in comparison with normotensive rats of Wistar-Kyoto strain (WKY) by using a Sep-Pak C18 cartridge directly connected to the perfusion system. We also examined effect of electrically-induced nerve stimulation on the release of immunoreactive Ang II in the two strains. High performance liquid chromatography demonstrated the presence of Ang II in the perfusate. The spontaneous release of immunoreactive Ang II was as high as about 300 to 500 pg/30 min, tended to be higher in SHR rats (435.0 +/- 68.2 pg/30 min) than in WKY rats (342.1 +/- 65.1 pg/30 min), and stable up to 3 hours of perfusion for both strains. Periarterial nerve stimulation elicited a significant increment in the release of immunoreactive Ang II in either SHR (p less than 0.02) or WKY rats (p less than 0.05); however, the amount of released immunoreactive Ang II evoked by nerve stimulation was significantly greater in SHR than in WKY rats (781.3 +/- 89.6 vs 498.8 +/- 54.6 pg/30 min, p less than 0.05). These results further provide evidence for local generation and release of Ang II in peripheral vascular tissues, and are consistent with the hypothesis that the vascular renin-angiotensin system is one of important factors responsible for the maintenance of blood pressure.

Angiotensin II↗

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.

6-Ketoprostaglandin F1 alpha↗

[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.

Calcium↗

[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.

Abnormalities, Multiple↗

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.

Adult↗

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.

Angiotensin II↗

[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.

11-beta-Hydroxysteroid Dehydrogenases↗

[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.

Aldosterone↗

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)

Adolescent↗