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Biomedical subjects

T Saruta

Publications and source records attributed to T Saruta.

At least 379 records · Page 21Linked to original sources
PubMed1991

Aldosterone synthase cytochrome P-450 expressed in the adrenals of patients with primary aldosteronism.

A human cytochrome P-450 with aldosterone synthase activity was purified from the mitochondria of an aldosterone-producing adenoma. It was recognized by an anti-bovine cytochrome P-450(11 beta) IgG and by a specific antibody raised against a portion of the CYP11B2 gene product, one of the two putative proteins encoded by human cytochrome P-450(11 beta)-related genes (Mornet, E., Dupont, J., Vitek, A., and White, P. C. (1989) J. Biol. Chem. 264, 20961-20967). A similar and probably the same aldosterone synthase cytochrome P-450 was detected in the adrenal of a patient with idiopathic hyperaldosteronism. These aldosterone synthases were distinguishable from cytochrome P-450(11 beta), the product of another cytochrome P-450(11 beta)-related gene, i.e. CYP11B1, by their catalytic, molecular, and immunological properties and also by their localization. The latter enzyme was unable to produce aldosterone and did not react with the specific antibody against the CYP11B2 gene product. It was present both in tumor and non-tumor portions of the adrenals carrying the adenoma and in normal adrenal cortex. On the other hand, aldosterone synthase cytochrome P-450 localized in the tumor portions of the adrenals or in the adrenal of a patient with idiopathic hyperaldosteronism. Thus aldosterone synthase cytochrome P-450, a distinct species from cytochrome P-450(11 beta), is responsible for the biosynthesis of aldosterone in the human, at least in patients suffering from primary aldosteronism.

Adenoma↗
PubMed1991

Effect of alpha-adrenergic blockade on blood pressure, glucose, and lipid metabolism in hypertensive patients with non-insulin-dependent diabetes mellitus.

To clarify the long-term effects of alpha-adrenergic blockade on blood pressure, glucose, and lipid metabolism, a selective alpha 1-adrenergic inhibitor (prazosin, 1.0 to 2.0 mg/day in divided doses) was administered as a single antihypertensive agent to 10 (four men and six women, aged 52 to 76 years) hypertensive patients (systolic blood pressure [SBP] greater than or equal to 150 mm Hg or diastolic blood pressure [DBP] greater than or equal to 90 mm Hg) with non-insulin-dependent diabetes mellitus (NIDDM) for up to 20 weeks. Blood pressure, glucose tolerance and immunoreactive insulin (IRI) response to 75 gm oral glucose load, hemoglobin A1 (Hb A1), serum lipid profile, and serum apolipoprotein were examined before and after treatment. SBP and DBP were significantly reduced at 20 weeks after treatment with the selective alpha 1-adrenergic inhibitor (SBP 167 +/- 6 mm Hg versus 152 +/- 7 mm Hg; DBP 81 +/- 3 mm Hg versus 76 +/- 3 mm Hg, (p less than 0.05 and p less than 0.01, respectively). Glucose tolerance and IRI response to glucose load were not significantly changed at 4 and 12 to 20 weeks after selective alpha 1-inhibitor treatment compared with the baseline data before treatment; the level of Hb A1 was not significantly changed at 4 and 20 weeks after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Effects of L-arginine on systemic and renal haemodynamics in conscious dogs.

1. The effects of L-arginine on systemic and renal haemodynamics were investigated in conscious dogs. L-Arginine was administered intravenously at doses of 15 and 75 mumol min-1 kg-1 for 20 min. 2. Mean arterial blood pressure, heart rate and cardiac output were not changed significantly by L-arginine infusion. However, L-arginine infusion induced a significant elevation of renal blood flow from 50 +/- 3 to 94 +/- 12 ml/min (means +/- SEM, P less than 0.01). 3. Simultaneous infusion of NG-monomethyl-L-arginine (0.5 mumol min-1 kg-1) significantly inhibited the increase in renal blood flow produced by L-arginine (15 mumol min-1 kg-1) without significant changes in mean arterial blood pressure or heart rate. 4. Pretreatment with atropine completely inhibited the L-arginine-induced increase in renal blood flow, whereas pretreatment with indomethacin attenuated it (63 +/- 4 versus 82 +/- 10 ml/min, P less than 0.05). 5. A continuous infusion of L-arginine increased renal blood flow in the intact kidney (55 +/- 3 versus 85 +/- 9 ml/min, P less than 0.05), but not in the contralateral denervated kidney (58 +/- 3 versus 56 +/- 4 ml/min, P greater than 0.05). 6. These results suggest that intravenously administered L-arginine produces an elevation of renal blood flow, which may be mediated by facilitation of endogenous acetylcholine-induced release of endothelium-derived relaxing factor and vasodilatory prostaglandins.

Animals↗
PubMed1991

Adrenocorticotropic hormone-independent bilateral adrenocortical macronodular hyperplasia as a distinct subtype of Cushing's syndrome. Enzyme histochemical and ultrastructural study of four cases with a review of the literature.

Four patients with adrenocorticotropic hormone (ACTH)-independent bilateral adrenocortical macronodular hyperplasia (AIMAH) were examined. All of them were men whose ages ranged from 37 to 52 years. Plasma cortisol levels were high, with a loss of diurnal rhythmicity, and plasma ACTH was undetectable. Adrenal cortisol secretion was not suppressed by dexamethasone, but it was ACTH responsive. Test results for corticotropin-releasing hormone (CRH) also were negative. Image analyses revealed a normal sella turcica and significantly enlarged adrenal glands, which showed enhanced uptake of isotope. Both adrenal glands in all cases were between 72 and 176 g in combined weight and were composed of, and distorted by, yellow nodules. Histologically, small cortical cells with or without lipid, occasional clear cells, and rare compact cells of the usual size were increased in number in the glandular cords. Enzyme histochemically, cortical cells showed weaker activity for 3 beta hydroxysteroid dehydrogenase and other enzymes than did usual cortisol-producing adenomas. Ultrastructurally, they had moderately to poorly developed smooth endoplasmic reticulum. Nonnodular areas of the cortex consisting of nonproliferating cells were atrophic and contained no compact cell zone. This is similar to the adrenal cortices attached to cortisol-producing adenomas. These features are unique to AIMAH and suggest the presence of a distinct subtype of Cushing's syndrome.

Adrenal Cortex↗
PubMed1991

Characteristics of a new angiotensin converting enzyme inhibitor: delapril.

Delapril, a nonsulfhydryl angiotensin converting enzyme (ACE) inhibitor, which has an indanylglycine moiety differing from the proline moiety of captopril or enalapril, is an esterified prodrug that is converted in vivo to its active metabolites. Delapril effectively inhibits rabbit lung ACE activity and lowers blood pressure in spontaneously hypertensive rats. Delapril has several characteristics that differ from captopril and enalapril, including high lipophilicity and weak bradykinin potentiating action. Delapril is a more potent inhibitor of vascular wall ACE activity than enalapril or captopril. It also shows a weaker potentiating action on the citric acid-induced cough in the guinea pig model compared with captopril and enalapril. In 12 out of 150 patients with essential hypertension who complained of cough during treatment with enalapril, changing to delapril resulted in resolution of the cough in 6 out of 12 of these patients: the percentage of patients in the total population with cough decreased from 8% to 4%.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Importance of the renin-angiotensin system in sodium regulation in essential hypertension.

To elucidate the effect of natriuretic and antinatriuretic factors on the excretion of an intravenous sodium load, we observed the natriuretic responses of 12 patients with essential hypertension (EHT) and 7 age- and sex-matched normotensive (NT) subjects following the intravenous administration of 1500 mL of normal saline over a 3 h period. After saline infusion, both groups showed increases in urinary sodium excretion (UNaV). The increases in glomerular filtration rate (GFR), atrial natriuretic peptide (ANP) and urinary dopamine excretion (UDAV) and the suppression of plasma renin activity (PRA) were similar in both groups. However, no significant change in blood pressure (BP) was seen in either group. Since significant negative linear correlations between the basal level of PRA and percent change in UNaV or GFR were seen only in EHT, we observed the influence of suppressing the renin-angiotensin system with a converting enzyme inhibitor. After a 7 day treatment with enalapril, GFR and UNaV in EHT after saline infusion were comparable to data obtained in the absence of enalapril, despite a reduction in preexpansion BP. Furthermore, a significant positive correlation between the basal BP and the percent increase in UNaV was seen among EHT after enalapril treatment. These results suggest that the state of the renin-angiotensin system is important in renal sodium excretion in EHT.

Adult↗
PubMed1991

Contribution of prostaglandins to pressure natriuresis in Dahl salt-sensitive rats.

To examine the role of prostaglandins on pressure natriuresis in Dahl salt-sensitive (DS) rat, the pressure-natriuresis relationships in DS and Dahl salt-resistant (DR) rats were characterized with or without indomethacin (2 mg/kg/h) by utilizing an in vivo renal perfusion study. When untreated, in the DS rat the pressure-natriuresis curve was blunted (P less than .05) and excretion of prostaglandin E2 (38 +/- 11 to 109 +/- 43 pg/min) was decreased in comparison to the DR rat. With indomethacin, the pressure-natriuresis curve in the DR rat was blunted, while no significant changes were observed in the DS rat. Plasma renin activity and concentration of atrial natriuretic peptide were not changed by the treatment of indomethacin in both strains. These results suggest that the decrease in renal prostaglandins, at least in prostaglandin E2, plays some role in blunting pressure natriuresis in DS rat.

Animals↗
PubMed1991

Hypophosphatemic osteomalacia in von Recklinghausen neurofibromatosis.

Skeletal lesions are not uncommon in von Recklinghausen neurofibromatosis. Most of them are considered to be dysplastic in nature. Association of osteomalacia or rickets with neurofibromatosis has been documented only rarely. Reported herein is a 40-year-old woman with known von Recklinghausen neurofibromatosis who presented with bone pain, multiple pseudofractures, marked increase in osteoid by bone biopsy, and hypophosphatemia with renal phosphate wasting. Treatment with oral phosphate and vitamin D was effective. A survey of the literature revealed that 34 similar cases have been reported in the past. Although the exact pathogenetic mechanism remains to be determined, osteomalacia in neurofibromatosis appears to be distinct from more common dysplastic skeletal affections of this disease, being characterized by later onset in adulthood as a rule, renal phosphate loss with hypophosphatemia, multiple pseudofractures in typical cases, and response to treatment with pharmacological dose of vitamin D with or without phosphate supplement.

Adult↗
PubMed1991

Different effects of low and high doses of endothelin on haemodynamics and hormones in the normotensive conscious dog.

The effects of low-dose endothelin on systemic haemodynamics and vasoactive hormones were examined in conscious dogs. In addition, we examined the effects of endothelin on pressor responses to noradrenaline and angiotensin II and the baroreflex regulation of heart rate in conscious dogs. Continuous infusion of 40 fmol/kg per min endothelin for 40 min induced a mild but significant reduction in mean arterial pressure from 89.1 +/- 1.7 to 82.7 +/- 2.0 mmHg (P less than 0.05), associated with decreases in total peripheral resistance 20 min later. A 400 fmol/kg per min dose of endothelin, on the other hand, induced a gradual elevation of mean arterial pressure from 89.2 +/- 2.3 to 96.8 +/- 2.0 mmHg (P less than 0.05), associated with increases in total peripheral resistance over 30 min. The 40 fmol/kg per min dose of endothelin infusion induced a significant reduction in plasma arginine vasopressin (AVP; P less than 0.05) and elevations of plasma atrial natriuretic peptide (ANP; P less than 0.05), plasma prostaglandin E2 (PGE2; P less than 0.05) and plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha; P less than 0.05). The 400 fmol/kg per min dose produced elevations of AVP, ANP, PGE2 and 6-keto-PGF1 alpha (P less than 0.05). Pressor responses to noradrenaline and angiotensin II were significantly attenuated during continuous infusion of 40 fmol/kg per min endothelin, whereas 400 fmol/kg per min endothelin did not induce any significant changes compared with the control. Furthermore, baroreflex sensitivity was attenuated with 40 fmol/kg per min endothelin but did not show any significant changes at 400 fmol/kg per min.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Role of platelet cytosolic calcium in the response to salt intake in normotensive subjects.

1. To investigate the role of cytosolic calcium in salt-induced hypertension, a high salt diet was given to young normotensive subjects with or without a family history of hypertension. 2. A high salt diet raised blood pressure significantly in normotensive subjects with a family history compared with the age and gender matched subjects without a predisposition to hypertension. 3. Platelet cytosolic calcium was increased in predisposed subjects in a control period before salt intake. 4. A positive correlation was observed between the changes in mean blood pressure and cytosolic calcium before high salt intake, although salt loading did not induce any significant change in cytosolic calcium. 5. These results suggest that cytosolic calcium plays a role in elevation of blood pressure induced by salt loading in subjects with a family history of hypertension.

Adult↗
PubMed1991

[Pharmacokinetics of cefpirome (CPR) in patients with impaired renal function].

The pharmacokinetics of cefpirome (CPR), a new injectable cephem, were studied in 9 patients with various degrees (classified by Ccr.) of impaired renal function. Serum and urinary concentrations of CPR were measured by bioassay. The pharmacokinetic analyses were based on a two compartment open model. As renal impairment increased, higher serum concentrations were maintained in beta-phase and higher urinary concentrations were kept over a long time, as well. As a conclusion, it is necessary to consider the adequate administration and dosage for patients with renal impairment to prevent side effects caused by the maintenance of cefpirome in serum over a long time.

Aged↗
PubMed1991

Pharmacokinetics of carumonam (AMA-1080) in patients with impaired renal function and in those undergoing hemodialysis.

The pharmacokinetics of carumonam (AMA-1080) were studied after a single intravenous 1.0-g dose was given to 26 subjects grouped according to their renal functions. Creatinine clearance (CLCR) was above 85, 50 to 84, 10 to 49, and below 10 ml/min/1.73 m2 in groups 1, 2, 3, and 4, respectively. All of the six patients in groups 4 were receiving maintenance hemodialysis, and they were studied both during and between hemodialysis sessions. Carumonam obeyed two-compartment model kinetics in all four group. The volume of distribution based on the area under serum concentration-time curve (Varea) did not differ significantly among the four groups, the mean value being 0.309 +/- 0.084 liter/kg. The elimination-phase (beta) half-lives were 1.53 +/- 0.36, 2.00 +/- 0.64, 5.08 +/- 1.85, and 12.8 +/- 4.1 h in groups 1, 2, 3, and 4, respectively. The 0- to 24-h cumulative urinary recoveries of carumonam were 83 +/- 11, 76 +/- 20, 58 +/- 25, and 12 +/- 9% of the administered dose in groups 1, 2, 3, and 4, respectively. The systemic and the renal clearances of carumonam decreased according to the severity of renal dysfunction, and the nonrenal clearance, which was calculated as the difference between renal and systemic clearances also decreased as CLCR decreased. A significant positive correlation existed between beta and CLCR (r = 0.847, P less than 0.01), and the beta of carumonam could be predicted by the following equation: beta (h-1) = 0.00460 X CLCR (ml/min/1.73 m2) + 0.049. Hemodialysis shortened the elimination-phase half-lives from 12.8 +/- 4.1 to 2.66 +/- 1.49 h in the six subjects in group 4. A 5-h hemodialysis in a hypothetical anephric subject weighing 60 kg was estimated to remove 51.4% of the drug present in the body at the start of hemodialysis.

Adult↗
PubMed1991

Removal of imipenem and cilastatin by hemodialysis in patients with end-stage renal failure.

The removal of imipenem and cilastatin by hemodialysis was studied in 14 (for imipenem) and 6 (for cilastatin) subjects. Following intravenous infusion of imipenem and cilastatin at a combined concentration of 10 mg/kg of body weight, drug levels in plasma were determined serially during off- and on-hemodialysis periods, which were 2 and 4 h, respectively. The biexponential decay of the drug levels in plasma was evident in each subject for both imipenem and cilastatin. Hemodialysis accelerated the elimination of both imipenem and cilastatin: the mean elimination-phase half-life of imipenem was shortened from 200 to 78 min, and that of cilastatin was shortened from 445 to 115 min. Hemodialysis clearance of imipenem and cilastatin was calculated by five different methods, each with intrinsic assumptions. The mean hemodialysis clearance of imipenem was estimated to be 74.08 +/- 13.29 ml/min, and that of cilastatin was estimated to be 65.0 +/- 8.6 ml/min, after consideration of various methodological limitations. It was estimated that in a hypothetical anephric patient weighing 60 kg, a 4-h hemodialysis treatment would remove 54.8% of the imipenem and 62.9% of the cilastatin present in the body at the start of dialysis.

Cilastatin↗
PubMed1991

Effects of high salt intake on dopamine production in rat kidney.

To examine the origin of increased urinary dopamine excretion (UDAV) during high salt intake, we measured UDAV from the innervated (INN) or the chronically denervated (DEN) kidney in rats fed either a high-salt (HS) or low-salt (LS) diet. UDAV of DEN [3.50 +/- 0.46 ng. min-1.inulin clearance (CIN)-1] and INN (4.00 +/- 0.59 ng. min-1.CIN-1) kidneys in the HS group showed a significant increase compared with that of the respective kidney in the LS group (DEN 1.42 +/- 0.12, INN 1.44 +/- 0.09 ng.min-1.CIN-1), whereas the effect of denervation on UDAV was not significantly different between two groups. We determined aromatic L-amino acid decarboxylase (L-AADC) activity and dopamine degradation rate of microdissected proximal convoluted tubules to study the changes in dopamine metabolism. L-AADC activity in the HS group showed a significant increase compared with that in the LS group, although there was no significant change in dopamine degradation rate. We conclude that the increase in UDAV during high salt intake was mainly caused by the enhancement of extraneural dopamine production by the kidney in rats. Dopamine-producing enzyme, but not its degradation in the tubular cells, plays a role in the regulation of extraneural dopamine production.

Animals↗
PubMed1991

Incidence and mortality patterns of malignancy and factors affecting the risk of malignancy in dialysis patients.

A questionnaire study was performed among 23,209 dialysis patients in 589 institutions together with a retrospective study at Keio University Hospital to determine the risk of malignancy and factors affecting the risk ratio in dialysis patients. The incidence and mortality were 1.4-fold and 1.9-fold higher in dialysis patients than the expected rates in the general population. Incidence and mortality were 1.9-fold and 2.6-fold higher in males than in females. The risk ratios were remarkably high in university hospitals, followed by public hospitals. However, there was no significant difference between those in private hospitals and in the general population. The incidence was very high during the first 6 months of dialysis treatment and rather low in the 7th-10th year. The risk ratio of malignancy was higher in younger patients. Beyond the age of 60, the influence of age was greater than that of renal failure. Malignancies of the digestive organs were frequent and constituted 56% of all malignancies. Frequencies of malignancy in the liver, colon, rectum, bladder and kidney were higher than expected, whereas in the pancreas the frequency was lower than expected. Metastasis of malignancy was observed in 30% of the cases. Our study demonstrated a slight to moderate overall increase in the risk of malignancy and a widely differing risk ratio of malignancy by organ involved, sex, age, hospital group, epidemiological index and length of dialysis treatment in a large single racial population of maintenance dialysis patients.

Adult↗