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Biomedical subjects

S Naomi

Publications and source records attributed to S Naomi.

At least 19 recordsLinked to original sources
PubMed1998

Endothelin-1 inhibits endothelin-converting enzyme-1 expression in cultured rat pulmonary endothelial cells.

BACKGROUND: The lung expresses large amounts of endothelin-converting enzyme-1 (ECE-1), which catalyzes a step in the biosynthesis of potent vasoactive endothelin-1 (ET-1) from the inactive intermediate big ET-1. Because there has been no report concerning a possible relationship between ET-1 and ECE-1, we investigated the effects of ET-1 on ECE-1 expression in cultured rat pulmonary endothelial cells. METHODS AND RESULTS: ECE-1 messenger RNA (mRNA) and protein expression in cultured endothelial cells were assayed by Northern and Western blotting, respectively. Incubation with ET-1 for 6 hours caused a significant decrease in ECE-1 mRNA expression. The action of ET-1 on ECE-1 mRNA expression was antagonized by pretreatment with BQ788, a specific ETB receptor antagonist, but not by pretreatment with BQ123, a specific ETA receptor antagonist. The expression of ECE-1 protein was also inhibited at 6 hours after incubation with ET-1. The effects of ET-1 on ECE-1 mRNA and protein expression were shown to be mimicked by ionomycin, a calcium ionophore, but not by 12-O-tetradecanoylphorbol 13-acetate, a protein kinase C activator. CONCLUSIONS: The present results demonstrate that ET-1 suppressed ECE-1 protein levels by inhibiting ECE-1 mRNA expression through the ETB receptor, suggesting the existence of a feedback action of ET-1 on ECE-1 in pulmonary endothelial cells.

Animals↗
PubMed1997

Pharmacokinetics of nicardipine enantiomers in healthy young volunteers.

OBJECTIVES: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. METHODS: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a crossover fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. RESULTS AND CONCLUSIONS: Serum concentration of (+)-nicardipine was approximately 2-3 times higher than that of (-)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3-2.8 times greater than that of the (-)-nicardipine (P < 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (-)-nicardipine, respectively, for the 40-mg dose.

Administration, Oral↗
PubMed1997

Endothelin converting enzyme-1 gene expression in the kidney of spontaneously hypertensive rats.

Abnormal renal handling of water and sodium is implicated in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). Alteration of renal endothelin-1 synthesis is also reported in SHR. Endothelin-1, a potent vasoconstrictor and regulator of sodium reabsorption in the nephron, has a pathophysiological potential in the development of hypertension. Because synthesis of bioactive endothelin-1 requires endothelin converting enzyme-1 (ECE-1), we investigated whether renal ECE-1 gene expression is altered in the kidney of SHR. Kidneys from both 4- and 12-week-old SHR and age-matched Wistar-Kyoto rats (WKY) were studied. ECE-1 mRNA in microdissected nephron segments was assessed by reverse transcription-competitive polymerase chain reaction, and ECE-1 protein level by Western blot. In 4-week-old SHR, ECE-1 mRNA was significantly increased in the proximal straight tubule, medullary thick ascending limb, cortical thick ascending limb, and inner medullary collecting duct. ECE-1 protein level was increased in both the outer and inner medulla. In 12-week-old SHR, ECE-1 gene expression was significantly increased in the proximal straight tubule, medullary thick ascending limb, and also in the glomeruli. Glomerular preproendothelin-1 mRNA expression was not different between the two strains at both 4 and 12 weeks. We conclude that high ECE-1 gene expression in the nephron, via increase of endothelin-1 synthesis, may promote sodium retention that contributes to the development and/or maintenance of hypertension in SHR.

Aging↗
PubMed1996

Magnesium metabolism in hyperthyroidism.

Changes in magnesium metabolism, along with those in sodium, were investigated in 17 patients with Graves' disease (14 females and 3 males, mean +/- SD, 44.8 +/- 12.2 years) and their relationship to plasma levels of thyroid hormones were assessed before and after treatment. Each patient was studied in hyperthyroid state and euthyroid state after treatment. Each patient was studied in hyperthyroid state and euthyroid state after treatment with methimazole. Treatment with methimazole increased the magnesium concentration both in erythrocytes (2.00 +/- 0.18 vs. 2.08 +/- 0.24 mmol/l cells, P < 0.05) and in serum (0.72 +/- 0.12 vs. 0.84 +/- 0.11 mmol/l, P < 0.001) but both urinary output and fractional excretion of magnesium decreased significantly (P < 0.05 and P < 0.001, respectively). The erythrocyte sodium concentration decreased with treatment (10.7 +/- 2.6 vs. 8.1 +/- 1.1 mmol/l cells, P < 0.001) but the serum sodium remained unchanged (140.9 +/- 1.9 vs. 140.9 +/- 2.1 mmol/l, NS). Urinary excretion of sodium also decreased with treatment (P < 0.05), but only changes in indices of magnesium metabolism (decrease in renal fractional excretion, rise in serum level) correlated significantly with those of the thyroid functions with treatment. These observations clearly indicate that in Graves' disease, the magnitude of magnesium metabolism alteration is closely related to the extent of the increase in thyroid hormones in plasma.

Adult↗
PubMed1995

Determination of (+)- and (-)-nicardipine concentrations in human serum and their correlation with the antihypertensive effect after oral administration of racemic nicardipine.

Serum (+)- and (-)-nicardipine concentrations were determined after oral administration of racemic nicardipine, and the relationship between the concentration of each enantiomer and the percentage change in blood pressure was investigated. Serum concentrations of (+) and (-)-nicardipine were assayed separately by a method combining high-performance liquid chromatography (HPLC) with gas chromatography - mass spectrometry (GS-MS). Linear relationships were found with serum concentrations of 0.25-80 mg x ml(-1) for both enantiomers of nicardipine with correlation coefficients of greater than 0.999. A single oral dose of 40 mg racemic nicardipine was given to 15 patients with essential hypertension. Serum (+)-nicardipine concentration was 2-3 times higher than the concentration of (-)-nicardipine 1, 2, and 3 after drug administration. The logarithmically transformed value of the serum (+)-nicardipine concentration was inversely correlated with the percentage change in systolic blood pressure, the correlation being statistically significant 1 and 2 h after drug administration, and also inversely correlated with the percentage change in diastolic blood pressure 1, 2 and 3 h after drug administration. However, the logarithmically transformed value of serum (-)-nicardipine showed no significant correlations with the percentage change in either systolic or diastolic blood pressure.

Administration, Oral↗
PubMed1994

Dietary NaCl restriction deteriorates oral glucose tolerance in hypertensive patients with impairment of glucose tolerance.

This study investigated whether the change of glycemic response to oral glucose loading with an increase of dietary NaCl intake is different between salt-sensitive and salt-resistant groups, or whether it is related to glucose tolerance on a low NaCl diet independent of salt sensitivity. The plasma glucose and insulin response to 75 g oral glucose intake was assessed on low (34 mmol/day) and high (342 mmol/day) NaCl diets in 31 patients with essential hypertension, and the area under the curve for both variables (AUCglu and AUCins) was calculated. The data on the high NaCl diet were corrected for change in hematocrit. The percentage change in systolic, diastolic, and mean blood pressure between the two diets was defined as the salt sensitivity index (SSI) for systolic blood pressure (SSISBP), diastolic blood pressure (SSIDBP), and mean blood pressure (SSIMBP), respectively. The mean values of both AUCglu and AUCins decreased significantly with increase of NaCl intake; however, there was no significant correlation between SSI (SSISBP, SSIDBP, or SSIMBP) and the percentage changes in AUCglu and AUCins. Meanwhile, the percentage changes in AUCglu and AUCins significantly correlated with the respective values of AUCglu and AUCins on the low NaCl diet. These results suggest that extreme NaCl restriction may deteriorate glucose metabolism in hypertensive patients, especially in those with diabetes mellitus or impaired glucose tolerance.

Adult↗
PubMed1994

Timing for administration of an antihypertensive drug in the treatment of essential hypertension.

To find the best timing for administration of long-acting antihypertensive drugs, we gave nitrendipine, a calcium antagonist of the dihydropyridine group, once a day to six hospitalized and drug-free patients with essential hypertension, changing the time of administration and studying the effects on the circadian rhythm of blood pressure. After control values of 24-hour blood pressure variations were taken with patients on placebo, a 10-mg tablet of nitrendipine was given for 3 days on three occasions--at 6 AM on awakening, at 8:30 AM after breakfast, and at 6 PM after supper; 24-hour blood pressure values for each period were recorded on the third day. The 24-hour blood pressure values during the control period showed a biphasic circadian rhythm, with higher values during wakefulness and lower values during sleep. The control period was also characterized by a rapid rise in blood pressure on awakening, the so-called morning surge of blood pressure, and a gradual decline during sleep at night. Although the morning surge was not completely suppressed by nitrendipine given after breakfast, it was diminished by the drug given on awakening or after supper; the latter brought a deeper decline in blood pressure during sleep compared with other times. The average of 24-hour blood pressure values obtained by nitrendipine given on awakening was the lowest among the three occasions. Thus, administration of long-acting calcium antagonists with a rapid onset of action on awakening in the early morning seems to be a more rational and beneficial alternative than the conventional administration after breakfast.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A case of Sipple's syndrome with malignant pheochromocytoma treated with 131I-metaiodobenzyl guanidine and a combined chemotherapy with cyclophosphamide, vincristine and dacarbazine.

A 39-year-old woman with Sipple's syndrome and a malignant pheochromocytoma (PHE) is presented. She is a member of a big family with this syndrome and had undergone bilateral, subtotal adrenalectomy because of bilateral PHE six years prior to the present admission. In 1989, a small nodule was identified in her right thyroid lobe by ultrasonography and was suspected to be a medullary thyroid carcinoma (MTC). Further examinations revealed the coexistence of multiple lung and liver masses. These tumors were considered to be metastases of PHE because of the increased urinary excretion of catecholamines as well as extremely high catecholamines both in the hepatic venous blood and in the cystic fluid of the liver tumor even though there was no apparent recurrences of PHE in the adrenal region. After surgical removal of the MTC in August, 1989, she was given 3.7 GBq of 131I-metaiodobenzyl guanidine (131I-MIBG) infusions twice--in October, 1989 and in August, 1990. 131I-MIBG showed a strong accumulation in the lung and liver masses on both occasions. Periodic increases in blood pressure and tachycardia with an excessive catecholamine secretion were observed over two weeks after the first treatment. However, this treatment was not effective in reducing urinary catecholamines nor the size of the metastatic tumors. She, therefore, underwent chemotherapy with cyclophosphamide, vincristine and decarbazine in 1991, which slightly but significantly reduced urinary excretion of catecholamines and the size of the lung tumors. She had clinically stable period for one year after the treatment but rapid growth of these metastatic tumors occurred afterwards and she died in August, 1992.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗
PubMed1993

Endogenous erythropoietin and salt sensitivity of blood pressure in patients with essential hypertension.

To investigate a possible involvement of endogenous erythropoietin (EPO) in the salt sensitivity of blood pressure in essential hypertensive (EHT) patients, plasma EPO concentrations were measured during different salt intakes in 14 patients with EHT. All patients were given low salt (34 mmol NaCl/day) and high salt (342 mmol NaCl/day) diet of 7 days each. The plasma EPO concentrations were significantly higher on the high salt diet than those of low salt diet (23.5 +/- 1.9 v 18.7 +/- 1.8 mIU/ml, mean +/- SD, P < .05). The percentage change of plasma EPO concentration with salt loading correlated positively with hematocrit (Ht) at high salt diet (r = -0.62, P < .02) and tended to be correlated with plasma hemoglobin at high salt diet (r = 0.52, P < .10). These results suggest that the secretion of EPO is increased in response to hemodilution caused by the salt loading and the increased EPO concentration in plasma which may contribute to the increase in blood pressure through an expansion of total blood volume due to an enhanced red cell generation in combination with salt and water retentions.

Adult↗
PubMed1993

The usefulness of the captopril test as a simultaneous screening for primary aldosteronism and renovascular hypertension.

The usefulness of the captopril test as a simultaneous screening method for primary aldosteronism (PA) and renovascular hypertension (RVH) was evaluated in 111 patients with essential hypertension, and in 79 patients with secondary hypertension, which included 16 patients with PA and 18 with RVH. Plasma renin activity (PRA, ng/mL/h) and plasma aldosterone concentration (PAC, ng/dL) were determined before and 90 min after administration of 50 mg of captopril in the supine position on a normal NaCl diet. A cutoff point or a discriminant function in the screening was determined by discriminant analysis. A quadratic discriminant function of PRA and PAC after the captopril test identified patients with PA with a false negative rate of 6.3% (1/16), and a false positive rate of 0.6% (1/174) which was significantly lower than that of 3.4% at the basal state (P < .05). In the screening for RVH, the criterion of a postcaptopril PRA of greater than 10.6 ng/mL/h had a false negative rate of 5.6% (1/18) and a false positive rate of 15.1% (26/172). This false positive rate was also significantly lower than that using a criterion for precaptopril PRA of 2.21 ng/mL/h (P < .05). Accordingly, the captopril test was a useful method in the simultaneous screening for PA and RVH, and it may be particularly applicable in specialized hypertension clinics.

Adult↗
PubMed1993

Vascular smooth muscle response to ouabain. Relation of tissue Na+ to the contractile response.

Smooth muscle responses to Na+ pump inhibition are thought to reflect two elements: a neurogenic contribution, involving catecholamine release from nerve terminals, and a myogenic response, attributed to relations between pump activity, [Na+]i, and [Ca2+]i. In the present study, we describe the time course and magnitude of cell Na+ changes, assessed by two methods, atomic absorption and nuclear magnetic resonance spectroscopy during the myogenic contractile response of rabbit aorta strips to ouabain. A threshold concentration of 3 x 10(-7) mol/L induced a gradual rise in [Na+]i. Both methods showed an essentially identical monotonic rise over 4 to 8 hours from a baseline level of 8 to 10 mmol/L water to a peak, which was approximately fivefold higher. The neurogenic (rapid) and myogenic (delayed and gradual) contractile responses were temporally distinct. Ouabain at 10(-7) mol/L, a concentration 10- to 100-fold lower than the threshold for catecholamine-dependent rapid-onset responses, induced only a delayed and gradual contractile response, which reached a maximum at 6 to 8 hours. With 10(-6) mol/L ouabain, the delayed response of 1.6 +/- 0.2 g peaked at 7.3 +/- 1.1 hours and was sustained for 16 hours. The time course was similar to that for change in [Na+] but somewhat later. Ouabain at 10(-5) and 10(-4) mol/L induced a delayed response that was identical in magnitude but also induced an early rapid contractile response, which was prevented by reserpine or phentolamine pretreatment. These agents did not influence the delayed response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Variation in apparent serum digitalis-like factor levels with different digoxin antibodies. The "immunochemical fingerprint".

Increased levels of a circulating digoxin-like factor (DLF) occur in a number of physiologic states in which sodium homeostasis is altered, and may contribute to the pathogenesis of hypertension. We exploited the different affinities for DLF of seven antisera directed at digoxin to develop an immunochemical profile, and then employed this index to address two questions: does the same DLF species exist in several conditions associated with increased DLF levels, including pregnancy, renal failure, hepatic failure, and neonatal cord blood? Will this approach prove useful in assessing candidates proposed to be DLF? An identical profile was identified in serum from pregnant women and patients with renal or hepatic failure, and a highly significant correlation existed between DLF levels measured with antisera of high and intermediate affinity in 42 subjects with increased levels (r = 0.93; P less than .001). In patients with renal failure, when endogenous DLF levels were too low to assess the profile, concentration of the serum resulted in measurable DLF levels that had an identical profile. The profile was somewhat altered in umbilical cord blood, perhaps reflecting an influence of increased steroid hormone levels. Among agents suggested as candidates for DLF, neither lysophosphatidylcholine nor ouabain showed a profile resembling DLF. Progesterone, 17-OH-progesterone, and bufalin, on the other hand, did show substantial similarity, perhaps providing a clue to the structure of DLF. The normal plasma levels of progesterone and 17-OH-progesterone are 100- to 1000-fold too low to be candidates for DLF and bufalin was sufficiently dissimilar not to be a candidate. DLF in at least three different patient populations probably represents identical chemical species.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1991

A possible contribution of endogenous atrial natriuretic peptide to proteinuria in patients with chronic renal failure.

Plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured with a specific radioimmunoassay in 19 undialysed patients with chronic renal failure. At the beginning, an extremely high level of plasma hANP (50 fmol/ml) seen in a patient was rejected with Smirnov's test and was excluded from further statistics. The plasma IR-ANP levels in these patients were significantly higher than those of 19 normal subjects matched with age and sex (10.9 +/- 1.6 vs 5.3 +/- 0.6 fmol/ml, mean +/- SEM, p less than 0.01), and positively correlated with mean blood pressure (r = 0.44, p less than 0.05) and the cardiothoracic ratio (r = 0.65, p less than 0.01), but did not correlate with creatinine clearance (r = -0.38, n.s.). Further, a significant correlation was observed between plasma IR-ANP and urinary protein output (r = 0.47, p less than 0.05). On the other hand, urinary protein output did not correlate significantly with variables such as mean blood pressure, the cardiothoracic ratio or creatinine clearance. Since it has been suggested that ANP enhances glomerular capillary permeability, increased ANP responding to volume overload in those patients may play an important role in increasing urinary protein excretion.

Adult↗
PubMed1991

Renal sodium handling and sodium transport inhibitor in salt-sensitive essential hypertension.

To investigate the mechanism whereby blood pressure rises with NaCl loading in salt-sensitive essential hypertension, salt-sensitivity index was determined along with sodium and lithium clearances, plasma Na+,K(+)-ATPase inhibitor and intra-erythrocyte sodium and potassium concentrations. Salt-sensitivity index was defined as the percentage of change in mean blood pressure when NaCl intake was changed from low (34 mmol/day) to high (342 mmol/day). Salt-sensitivity index was inversely correlated with fractional excretion of lithium both on the low and high NaCl diets (r = -0.721, P less than 0.01 and r = -0.591, P less than 0.02, respectively; n = 16), but not with fractional excretion of sodium. The change of plasma Na+,K(+)-ATPase inhibition with NaCl loading had a direct correlation with salt-sensitivity index (r = 0.704, P less than 0.01; n = 16). Either intra-erythrocyte sodium and potassium concentrations or the ratio of these two values did not change significantly with an increase of dietary NaCl intake. These results suggest that an enhancement of proximal tubular sodium reabsorption stimulates secretion of plasma Na+,K(+)-ATPase inhibitor which may be involved in a rise in blood pressure with sodium loading. They also suggest that lithium clearance is a determinant which can predict salt sensitivity without actual NaCl loading.

Biological Transport↗
PubMed1990

Role of carbohydrate moiety of IL-5. Effect of tunicamycin on the glycosylation of IL-5 and the biologic activity of deglycosylated IL-5.

IL-5 is a T cell-derived lymphokine that induces B cell growth and differentiation in murine systems. In this study, we examined the role of carbohydrate moiety of IL-5 in the expression of biological function. IL-5 polypeptides translated in Xenopus oocytes were heterogeneous in terms of isoelectric point (pI 4.7 to 8.0) and m.w. (45,000 to 60,000 under nonreducing conditions) and yielded m.w. of 25,000 to 30,000 under reducing conditions. Treatment of rIL-5 with N-glycanase under reducing conditions yielded an IL-5 monomer of m.w. 12,000 to 14,000. Furthermore, deglycosylated rIL-5 that had been translated in the presence of tunicamycin showed very limited heterogeneity by two-dimensional gel electrophoresis (first dimension, nonequilibrium pH gradient electrophoresis; second dimension, SDS-PAGE). The m.w. was 27,000 to 28,000 under non-reducing conditions and migrated to m.w. 13,000 to 14,000 under reducing conditions. These results indicate that IL-5 is a glycoprotein carrying the N-glycosidically-linked carbohydrates. Treatment of IL-5 with sialidase caused the decrease in the heterogeneity in isoelectric point of IL-5. Deglycosylated rIL-5 that had been obtained from tunicamycin-treated oocytes could bind to IL-5-responding cells (T88-M), which express both high- and low-affinity IL-5 receptors, as efficient as intact rIL-5 under high-affinity conditions. Scatchard plot analysis of equilibrium binding of 35S-labeled rIL-5 to T88-M cells revealed that the dissociation constants (Kd) of glycosylated rIL-5 and deglycosylated rIL-5 were 127 pM and 110 pM, respectively. IL-5 activities determined by both B cell growth and differentiation assays were not affected by deglycosylation. These results indicate that N-linked glycoside moiety of IL-5 molecules may not play an essential role in the expression of its activity.

Animals↗
PubMed1990

Localization of aldosterone-producing adenoma: venous sampling in primary aldosteronism.

Adrenal venous sampling of blood was performed for nine patients with aldosterone-producing adenoma (APA). Measurement of adrenal venous aldosterone is useful for localization of APA but difficult, because catheterization of the right adrenal vein is not easy, and the blood is diluted by nonadrenal flow. To solve these problems, levels of aldosterone (A; ng/dl) and cortisol (C; micrograms/dl) were measured in samples from the left adrenal vein (LAV) and the inferior vena cava (IVC), and the LAV A/C and (LAV A/C)/(IVC A/C) ratios were calculated. These ratios were also obtained for 16 patients with essential hypertension. The adenoma could be localized in three of the nine cases by the measurement of aldosterone alone, but the use of a LAV A/C ratio greater than 5 x 10(-3) and a (LAV A/C)/(IVA A/C) ratio less than 1.0 as criteria separated the patients into those with a left APA, right APA, or essential hypertension. Consequently, adrenal venous sampling and the calculation of these ratios enables preoperative localization of APA with more accuracy, especially when the tumor is small or the result of CT and adrenal scintigraphy is not consistent.

Adenoma↗