Variant forms of primary aldosteronism: reconsideration of the differential diagnosis and treatment.
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Diagnosis, Differential↗
Biomedical subjects
K Naruse
Publications and source records attributed to K Naruse.
Effects of beraprost sodium and insulin on the electroretinogram, nerve conduction, and nerve blood flow in rats with streptozotocin-induced diabetes.
The effect of a prostacyclin analog, beraprost sodium, on the electroretinogram, motor nerve conduction velocity, and nerve blood flow was determined in rats with streptozotocin-induced diabetes and was compared with the effect of insulin. Beraprost sodium (0.01 mg x kg-1 x day-1 for 8 weeks) significantly shortened the peak latency of the electroretinogram b-wave, increased tail nerve conduction velocity, and increased sciatic nerve blood flow in diabetic rats (P < 0.0003, 0.0001, and 0.0001 vs. untreated diabetic rats, respectively). This was accompanied by a significant increase in the 6-keto-prostaglandin F1alpha content of the thoracic aorta and a marked increase in the cAMP content of the sciatic nerve. Beraprost sodium had no effect on the sorbitol and fructose contents of the sciatic nerve and retina, but insulin (8-10 U/day) significantly reduced both parameters. These findings suggest that beraprost sodium may be useful for prevention of vascular and neural dysfunction in the retina and peripheral nerve.
6-Ketoprostaglandin F1 alpha↗
Effect of propionyl-L-carnitine on motor nerve conduction, autonomic cardiac function, and nerve blood flow in rats with streptozotocin-induced diabetes: comparison with an aldose reductase inhibitor.
The effects of propionyl-L-carnitine (PCAL) on caudal motor nerve conduction velocity, the coefficient of variation of the R-R interval on the electrocardiogram, and sciatic nerve blood flow were compared with those of [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate, an aldose reductase inhibitor, in rats with streptozotocin-induced diabetes. Diabetic control rats showed significantly delayed nerve conduction (P < .05), decreased R-R variability (P < .05) and reduced sciatic nerve blood flow (P < .05). Oral administration of PCAL (0.5 g/kg/day) and [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (0.05% in the diet: 60 mg/kg/day) for 8 weeks significantly improved both nerve conduction (P < .05) and R-R variability (P < .05) in diabetic rats, along with the normalization of sciatic nerve blood flow. PCAL treatment increased the nerve tissue levels of carnitine and myo-inositol and reduced the serum triglyceride level in diabetic rats. Our results suggests that PCAL could have therapeutic potential for the treatment of diabetic neuropathy.
Aldehyde Reductase↗
[SA channels are mechanosensors of cells?].
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Animals↗
Large-scale preparation and function of porcine hepatocyte spheroids.
To obtain a large number of porcine hepatocyte aggregates (spheroids) that have great potential in a bioartificial liver (BAL), we performed spheroid formation at a high cell density in a 1-L-scale spinner flask fitted with a silicon tubing apparatus for oxygen supply. We thereby obtained, within 24 hours, approximately fifty times more porcine hepatocyte spheroids as compared with the results of previous reports. The amount obtained corresponds to 2.5x10(9) cells and to roughly one-sixth of the cell number required for a BAL for a human patient. When we cultured spheroids continuously in suspension, they expressed three times more albumin secretion and twice the ammonium removal as compared with conventional monolayers during 10 days culture. Collagen gel entrapment of spheroids particularly lowered albumin secretion. We therefore conclude that the supension culture vessel of porcine hepatocyte spheroids is one of the most promising module types.
Albumins↗
Development of a new bioartificial liver module filled with porcine hepatocytes immobilized on non-woven fabric.
We developed a new bioartificial liver module, a non-woven fabric (NWF) module, which was filled with hepatocytes immobilized on non-woven polyester fabric, and compared its efficacy with a suspension culture vessel. Porcine hepatocytes were isolated from whole pig liver, which formed spheroids in a 1L suspension culture vessel. Some of these spheroids were allowed to construct a 50 mL NWF module by inoculation onto 12 sheets of disk-shaped non-woven fabric then stuffed into a 50 mL column. The remaining spheroids were transferred to a 100 mL spinner flask and placed in suspension. The 50 mL NWF module maintained a much better metabolic and synthetic function than the 100 mL suspension culture vessel throughout the study. Based on these results, we developed a 200 mL radial-flow-type NWF module. This module filled with single hepatocytes showed promising efficiency.
Animals↗
[Pseudohypoaldosteronism].
Mineralocorticoid resistance results from inability of aldosterone to exert its effect on its target tissues. The syndrome is associated with salt loss, hypotension and hyperkalemic acidosis. We have cloned and sequenced the cDNA of the mineralocorticoid receptor of five sporadic cases with this syndrome but have found no mutations of pathophysiological significance, which would explain the resistance of these patients to aldosterone. In all of these patients, we also examined 0.9 kb of the 5' regulatory region and the first untranslated exon of the mineralocorticoid receptor gene, without detecting any abnormalities. We are now studying the subunits of the amiloride-sensitive sodium channel (ENaC), which are in the postreceptor pathway of aldosterone action, in this disease.
Aldosterone↗
Comparisons of porcine hepatocyte spheroids and single hepatocytes in the non-woven fabric bioartificial liver module.
We previously developed a new bioreactor of the bioartificial liver composed of non-woven fabric. We have also experimented with hepatocyte spheroids, with the aim of improving the efficiency of this NWF bioreactor. In this study, we compared the efficiencies of NWF bioreactors employing hepatocyte spheroids versus single hepatocytes. Hepatocytes were isolated from a whole pig liver by Seglen's method. 1.0 x 10(10) single hepatocytes were immobilized in the NWF bioreactor. Another 1.0 x 10(10) hepatocytes were allowed to form spheroids by 24 hr suspension culture in a 4-L culture vessel, before being immobilized in the bioreactor. Hepatocyte spheroids were found to be functionally superior, on a per-cell basis, to single hepatocytes in the NWF bioreactor. However, the NWF bioreactor employing hepatocyte spheroids exhibited lower efficiency than thaT employing single hepatocytes, because the total number of the hepatocytes had decreased during the 24 hr suspension culture.
Animals↗
Polyol pathway, 2,3-diphosphoglycerate in erythrocytes and diabetic neuropathy in rats.
The relationship between the 2,3-diphosphoglycerate concentration in red blood cells as a biological indicator of tissue hypoxia and diabetic neuropathy, and the effect of a potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2'5'-dioxospiro [chroman-4,4'-imidazolidine]-2-carboxamide (SNK-860), on both were investigated in streptozotocin-induced diabetic rats. Diabetic rats demonstrated significantly delayed motor nerve conduction velocity and reduced sciatic nerve blood flow. Altered biochemical features in the sciatic nerves, including a marked accumulation of sorbitol and fructose, myo-inositol depletion and decreased Na+/K(+)-ATPase activity were also detected in diabetic rats. These defects were accompanied by a decrease in the red blood cell 2,3-diphosphoglycerate concentration. Treatment with SNK-860 partially or completely ameliorated these abnormalities. These observations suggest that a decrease in the red blood cell 2,3-diphosphoglycerate concentration is one of the factors contributing to tissue hypoxia, which results in diabetic neuropathy, and that this decrease is mediated through an aldose reductase inhibitor-sensitive pathway.
2,3-Diphosphoglycerate↗
Differential gene expression of vascular natriuretic peptide receptor subtype in artery and vein.
Although the vasorelaxation by natriuretic peptide (NP) is much less potent in the vein than in the artery, mechanism underlying the phenomenon remains unknown. Since NP receptor consists of three subtypes with different functions, we determined the mRNA level of each NP receptor subtype in the artery and vein by ribonuclease protection assay. In the aorta, NP-A receptor related to the biological action of NP was the predominant form. By contrast, NP-C receptor related mainly to the clearance of NP was the predominant form in the inferior vena cava: NP-C mRNA level was about two fold higher than in the aorta, while both NP-A and NP-B receptor mRNA levels were about half of that in the aorta. These results provide the molecular basis for the different biological response to NP in the artery and vein. Differential gene expression of NP receptor subtype could be an important determinant of the biological actions of NP.
Animals↗
In vivo transfection of genes for renin and angiotensinogen into the glomerular cells induced phenotypic change of the mesangial cells and glomerular sclerosis.
Locally activated renin angiotensin system plays an important role in the progression of the glomerular diseases. In order to understand the local effect of overexpressed angiotensin II in the glomerulus in situ, we introduced human genes for renin and angiotensinogen into the rat kidney by hemagglutinating virus of Japan-liposome procedure. Three days after transfection human renin was detected in the glomeruli by immunohistochemistry. Seven days after transfection, extracellular matrix was expanded in the glomeruli and alpha-smooth muscle actin was expressed in the mesangial cells. These results suggest that locally activated renin angiotensin system induces glomerular sclerosis and a phenotypic change in mesangial cells.
Actins↗
Trends in nonmelanoma skin cancer in Japan.
We compared the prevalence of skin cancer and solar keratosis (SK) in patients who attended 26 Japanese university hospitals between 1976-1980 with those who attended between 1986-1990 to investigate whether the incidence of skin cancer has increased or not. Age-adjusted incidence rates of basal cell carcinomas (BCC) and SK, but not squamous cell carcinomas (SCC), from 1986-1990 were higher than those from 1976-1980. In addition, a population-based incidence study was conducted in Kasai City, Hyogo prefecture, to establish the frequency of skin cancer and SK. A total of 4736 people over 20 years of age were examined. Two BCC and 36 SK patients were identified clinically and histopathologically. SCC was not found. Age-adjusted incidence rates of BCC and SK per 100,000 were 16.5 and 486.1, respectively. The BCC incidence rate in Kasai City was significantly higher than the incidence of Japanese nonmelanoma skin cancer (NMSC) reported by Gordon in 1976. Further, subjects classified as skin type I showed statistically higher SK prevalence rates compared to skin types II and III. The present study indicates that the prevalences of NMSC and SK in Japanese have increased during the last three decades and that skin type I may be a risk factor for NMSC in Japanese.
Adolescent↗
Insulin resistance is associated with high plasma ouabain-like immunoreactivity concentration in NIDDM.
The aim of the present study was to elucidate the pathophysiologic significance of circulating ouabain as a link between insulin resistance (IR) and hypertension (HT) in NIDDM. Euglycaemic (4.5 mmol/l) hyperinsulinaemic (360-580 pmol/l) clamping was performed using an artificial endocrine pancreas. Plasma ouabain-like immunoreactivity (OLI) was determined by radioimmunoassay using a highly specific antibody to ouabain. HT was defined as systolic blood pressure > 140 mm Hg and/or diastolic > 90 mm Hg or being treated with antihypertensive agents. The values (mean +/- SEM) of glucose infusion rate (GIR) and plasma OLI were compared among the four groups classified using IR and HT as factors. Group I (IR-/HT-, n = 15): GIR 7.20 +/- 0.36 mg.kg-1.min-1, OLI 130.8 +/- 20.9 pmol/l, which was not different from that in eight normal control subjects (7.69 +/- 0.40 mg.kg-1.min-1 and 142.6 +/- 32.3 pmol/l, respectively); Group II (IR-/HT+, n = 13): 5.89 +/- 0.36 mg.kg-1.min-1, 172.5 +/- 35.0 pmol/l; Group III (IR+/HT-, n = 14) 1.91 +/- 0.28 mg.kg-1.min-1, 576.6 +/- 161.5 pmol/l (p < 0.01 vs Group I and II); Group IV (IR+/HT+, n = 15) 1.79 +/- 0.22 mg.kg-1.min-1, 703.1 +/- 170.1 pmol/l (p < 0.01 vs Group I and II), respectively. Six of 57 NIDDM patients studied exhibited very high (> 1500 pmol/l) plasma OLI concentrations, showed marked insulin resistance and were all hypertensive. When analysed as a whole, plasma OLI was negatively correlated with GIR (p < 0.001), but was not correlated with arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Effects of an aldose reductase inhibitor on erythrocyte fructose 3-phosphate and sorbitol 3-phosphate levels in diabetic patients.
Fructose 3-phosphate and sorbitol 3-phosphate are novel metabolites that have been shown to associate with the polyol pathway in animal experiments. Fructose 3-phosphate is of particular interest because of its potent glycation capability as compared with other glycolytic intermediates, e.g., fructose. We observed the effects of treatment with epalrestat, an aldose reductase inhibitor, on their concentrations in erythrocytes from diabetic patients. The levels of both metabolites were significantly higher in diabetic patients than in non-diabetic subjects. A group of patients who had been treated with epalrestat showed significantly lower levels of both metabolites as compared with those untreated. A treatment of three patients with epalrestat for one month resulted in obvious decreases in their concentrations. The results suggest a possible explanation for the preventive effect of an aldose reductase inhibitor on nonenzymatic glycation.
Adult↗
Abnormal arachidonate distribution in low-density lipoprotein and thoracic aorta in hyperinsulinemia.
The mechanism by which hyperinsulinemia promotes atherogenesis is unknown. The effects of hyperinsulinemia on risk factors for atherosclerosis were investigated by subcutaneously injecting rats daily with an insulin-zinc suspension (20 U/kg) for 12 weeks. After this period, body mass and food consumption did not differ significantly between control and insulin-treated animals. Daily insulin injection significantly increased urinary excretion of epinephrine and decreased urinary excretion of norepinephrine and dopamine, but had no significant effect on blood pressure or heart rate. Although insulin decreased plasma triglyceride concentration by 44% (P < .01), the triglyceride to protein ratio in plasma low-density lipoprotein (LDL) was increased by 34% (P < .05) in insulin-treated rats; the cholesterol to protein and triglyceride to protein ratios remained unaffected, indicating a change in the quality of the LDL particle. Insulin also increased the percentage of arachidonic acid (20:4) in LDL triglycerides by 37% (P < .05). In contrast, cholesteryl esters and triglycerides in the thoracic aorta were significantly increased (49% and 91%, respectively) by insulin treatment. Insulin increased the percentage of monounsaturated fatty acids and decreased the percentage of n-6 fatty acids, including arachidonate, in aortic triglycerides. Insulin also increased the percentage of palmitoleic acid (16:1) and decreased the percentages of saturated fatty acids and n-6 fatty acids in aortic cholesteryl esters. These results indicate that insulin induced deposition of cholesteryl esters and triglycerides, especially those containing monounsaturated fatty acids, and abnormal arachidonate distribution in LDL and tissues. The data further suggest that the development of atherosclerosis in response to hyperinsulinemia may be associated with arachidonate-rich triglycerides in LDL.
Animals↗
Prevention of abnormalities in motor nerve conduction and nerve blood-flow by a prostacyclin analog, beraprost sodium, in streptozotocin-induced diabetic rats.
The effects of the prostacyclin analog beraprost sodium on motor nerve function and nerve blood-flow were examined in streptozotocin-induced diabetic rats. Oral administration of beraprost sodium 0.1 mg/kg/day for 8 wks significantly (P < 0.001) improved caudal motor nerve conduction velocity and sciatic nerve blood-flow, both of which are impaired in diabetic rats. Beraprost sodium did not affect glucose, sorbitol, or fructose levels in the sciatic nerve. However, a decreased content of cyclic AMP in the sciatic nerve and higher level of thromboxane B2 in the thoracic aorta of diabetic rats, as compared with those in normal rats, were reversed by the treatment with beraprost sodium (P < 0.01). Results suggest that beraprost sodium may have value in treating diabetic neuropathy, mainly by improving endoneurial blood-flow.
Animals↗
Gene expression of vascular natriuretic peptide receptor in the aorta of hypertensive rats.
1. To elucidate the pathophysiologic role of vascular natriuretic peptide (NP) receptor in hypertension, we determined NP-A and NP-B receptor mRNA levels by means of ribonuclease protection assay in aorta of three types of hypertensive rats. 2. The NP-A receptor mRNA level was higher in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) and deoxycorticosterone acetate-salt hypertensive rats than that in their respective control rats. On the contrary, the NP-A receptor mRNA level was lower in NG-nitro-L-arginine-methyl ester (L-NAME)-induced hypertensive rats compared with that in the control. 3. The NP-B receptor mRNA level did not show any significant change in all three hypertensive rats compared with their respective controls. 4. The present study suggests that high blood pressure is not the major factor regulating the NP receptor gene expression and also that the receptor subtype is independently regulated from each other.
Animals↗
Effect of an aldose reductase inhibitor, SNK-860, on deficits in the electroretinogram of diabetic rats.
To determine the effect of an aldose reductase inhibitor, SNK-860, on the worsening of the electroretinogram (ERG) during a diabetic state, rats with streptozotocin-induced diabetes were administered SNK-860 (1 or 4 mg kg-1 orally) daily for 4 weeks. The effectiveness of SNK-860 in prolonging the peak latencies of oscillatory potentials in the b-wave of the electroretinogram of diabetic rats varied between these different waveform components (designated O1, O2 and O3). SNK-860 (4 mg kg-1 day-1) either completely or partially prevented the prolonged peak latencies at O1 and sigma(O1 + O2 + O3). The drug failed to shorten the latency of the O2 and O3 components, and produced only a modest reduction in retinal levels of sorbitol and fructose, with no increase in myo-inositol. There was a significant correlation between the state of the ERG (components O1 and sigma(O1 + O2 + O3)) and the retinal levels of sorbitol and fructose (P < 0.01), but not of myo-inositol. It is concluded that a better understanding of the mechanism by which SNK-860 acts may provide new insight into the pathogenesis of hyperglycaemic retinal dysfunction and help to establish effective therapy for diabetic retinopathy.
Aldehyde Reductase↗