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Biomedical subjects

T Ebara

Publications and source records attributed to T Ebara.

At least 37 records · Page 2Linked to original sources

Decrease of serum ascorbic acid concentrations in patients with diabetic macroangiopathy.

The relationship between serum ascorbic acid (AA) and diabetic macroangiopathy was studied. Fifty-six patients with noninsulin-dependent diabetes mellitus were examined, together with 20 healthy controls matched for age against the diabetes patients. Aortic pulse wave velocity (PWV) was taken as an index of the severity of atherosclerosis. The level of serum AA in diabetic patients was significantly lower than that of the controls. Among the diabetic groups, those with elevated PWV levels by age demonstrated a significant drop in AA. No significant differences were seen in the level of serum dehydroascorbic acid (DHAA) between patients and controls, nor were there any significant differences among patient groups. The concentration of serum AA was inversely related to the risk factors of atherosclerosis, such as body mass index, Apo B/ Apo A-I ratio, thiobarbituric acid-reactive substances (TBARS), and microalbumin in urine. It was inferred from these findings that the depletion of serum AA was apparent in diabetics with advanced atherosclerosis.

Adult↗

Intracellular apoprotein B degradation is suppressed by decreased albumin concentration in Hep G2 cells.

It is generally accepted that hepatic secretion of apoprotein (apo) B-containing lipoproteins is substantially increased in nephrosis. To elucidate the mechanisms for the oversecretion of apo B, we investigated the effect of a various concentration of albumin on apo B kinetics in the absence or presence of oleate in Hep G2 cells. Hep G2 cells were labeled with [3H]-leucine in leucine-free medium containing 0, 1.5, 3.0 or 4.5% BSA for 180 minutes, and the secreted radiolabeled apo B, apo A1 and albumin were isolated by immunoprecipitation and counted. The secretions of apo B and albumin were suppressed by BSA (bovine serum albumin) in a dose-dependent manner, but the secretion of apo A1 was not suppressed significantly. Oleate (0.4 mM) increased the rate of apo B secretion by 2.5-fold when oleate was bound to 1.5% BSA, but at higher concentrations of BSA (3.0 or 4.5%), apo B secretion was less responsive to oleate. A pulse-chase study indicated that early apo B degradation was significantly suppressed in cells incubated with lower concentrations of BSA (0 or 1.5% BSA), thereby rapidly stimulating apo B secretion. Oleate (0.4 mM) potently inhibited apo B degradation when oleate was bound to 1.5% BSA, whereas the inhibition was not observed when oleate was bound to 4.5% BSA. Intracellular albumin synthesis was stimulated in BSA-free medium, but intracellular decay of albumin was essentially unaffected by concentration of BSA. Similar to BSA, a higher concentration of dextran (3.0 or 4.5%) reduced apo B secretion, and this was the result of increased early apo B degradation in the cells. These results indicate that reduced albumin suppresses intracellular apo B degradation, and the inhibition of apo B degradation by oleate is manifested only at a low concentration of albumin. Therefore, the present study suggests that free fatty acids bound to low concentration of albumin in the circulating plasma play an important role on hepatic oversecretion of apo B-containing lipoprotein in hypoalbuminemic state, such as nephrotic syndrome.

Apolipoprotein A-I↗

Attenuation of adrenomedullin-induced renal vasodilatation by NG-nitro L-arginine but not glibenclamide.

1. The present study was conducted in order to elucidate the in vivo contribution of nitric oxide (NO) and the glibenclamide-sensitive potassium channel in the renal action of adrenomedullin in anaesthetized dogs. 2. Intrarenal arterial infusion of adrenomedullin (20 ng kg-1 min-1) elicited a pronounced increase in renal blood flow with no changes in systemic blood pressure. The renal vasodilator action of adrenomedullin was markedly attenuated by pretreatment with NG-nitro L-arginine (L-NOARG), but this was reversed by continuous infusion of L-arginine. 3. Pretreatment with glibenclamide almost completely blocked the renal vasodilatation induced by lemakalim, but had no effect on the renal vasodilator and diuretic action of adrenomedullin. 4. Intrarenal arterial infusion of adrenomedullin induced diuresis and natriuresis. Diuretic and natriuretic action of adrenomedullin was also attenuated by L-NOARG. L-Arginine partly reversed the effect of L-NOARG and adrenomedullin-induced diuresis and natriuresis. 5. These data indicate that the in vivo renal vasodilator action of adrenomedullin is mediated by the release of NO. The glibenclamide-sensitive potassium channel is not involved in the renal action of adrenomedullin, at least, not in anaesthetized dogs. Since the inhibition of L-NOARG of adrenomedullin-induced diuresis occurred concomitantly with the attenuation of the renal vasodilator action of adrenomedullin, direct involvement of NO in adrenomedullin-induced diuresis remains to be established.

Adrenomedullin↗

Effect of adrenomedullin on renal hemodynamics and functions in dogs.

In order to elucidate the role of adrenomedullin in the kidney, we investigated the effects of adrenomedullin on renal hemodynamics and urine formation in anesthetized dogs. Intrarenal arterial infusion of adrenomedullin (0.8, 4 and 20 ng.kg-1.min-1) elicited dose-dependent increases in renal blood flow (by 10, 26 and 37%, respectively) with no change in blood pressure or heart rate, indicating a renal vasodilatory action of adrenomedullin. The glomerular filtration rate did not increase with the lower two doses, but increased marginally by 9% at the highest dose. Infusion of adrenomedullin at the rates of 4 and 20 ng.kg-1.min-1 increased urine flow and the urinary excretion of sodium and potassium dose dependently. Arterial and renal venous plasma renin activity was unaffected by adrenomedullin. These findings indicate that adrenomedullin is a potent renal vasodilatory peptide with a diuretic action. Since the threshold for the renal vasodilatory action of adrenomedullin is close to its physiological concentration in human plasma, adrenomedullin may play an important role in the regulation of renal function.

Adrenomedullin↗

Hyperlipidemia in streptozocin-diabetic hamsters as a model for human insulin-deficient diabetes: comparison to streptozocin-diabetic rats.

Characteristics of the lipoprotein profile and metabolism of triglyceride-rich lipoproteins in diabetic hamsters were investigated to assess their suitability as a model for human diabetic hyperlipidemia. Diabetes was induced in the hamsters by intraperitoneal injection of streptozocin (30 mg/kg) for 3 days and compared with the results in streptozocin-diabetic rats (50 mg/kg intravenously). Similar degrees of hyperglycemia and hypoinsulinemia were observed 8 to 10 days after the final streptozocin injection in both groups. Fasting plasma lipid concentrations were about 2.5 times greater in hamsters than in rats. Plasma cholesterol was principally associated with high-density lipoprotein (HDL) in both rodents, although the distribution in very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was significantly greater in hamsters (44%) than in rats (13%). Diabetes increased the concentrations of triglyceride, cholesterol, and phospholipid 5.6- to 7.8-fold in hamsters, whereas it increased them only 1.3- to 1.6-fold in rats. Diabetic hamsters have a plasma lipoprotein profile similar to that of diabetic man, ie, triglyceride-rich lipoproteins are increased and HDL cholesterol is decreased. The concentration of HDL cholesterol was inversely correlated with the severity of hypertriglyceridemia (r = .76, P < .005). This combination of events does not occur in diabetic rats. Hamsters had a low level of apoprotein B-48-containing triglyceride-rich lipoproteins, although diabetes increased the estimated concentration by fourfold. In rats apoprotein B-48 is the predominant form, but diabetes did not alter the relative proportion of apoprotein B isoforms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mechanism of hypertriglyceridemia in Dahl salt-sensitive rats, an animal model of spontaneous nephrotic syndrome.

It has been reported that focal and segmental glomerulosclerosis (FSGS) with pronounced proteinuria rapidly develop in Dahl salt-sensitive hypertensive (DS) rats fed a high-salt diet. We found that even when they are fed a standard rat chow (0.3% NaCl), DS rats, especially males, exhibit marked proteinuria, hypoalbuminemia, and hypertriglyceridemia without marked hypertension at 32 to 38 weeks of age. The nephrosis was associated with spontaneously developed FSGS. We therefore investigated the mechanism of hypertriglyceridemia in nephrotic animals. Plasma triglyceride (TG) and apoprotein (apo) B levels were markedly increased in DS rats compared with Sprague-Dawley (SD) rats, and this was mainly attributable to an increase in the concentration of very-low-density lipoprotein (VLDL). The TG secretion rate estimated by the Triton WR1339 method was significantly greater in DS rats. VLDL-TGs isolated from both the DS and SD rats were endogenously radiolabeled with different isotopes, and a mixture of these was then injected into DS and SD recipients. The half-life of VLDL-TG was about three times longer in DS recipients, regardless of the source of VLDL. In SD recipients, VLDL from DS rats was cleared at a slower rate than VLDL from SD rats. The activity of lipoprotein lipase in postheparin plasma was substantially decreased in DS rats. Isoelectric focusing gel electrophoresis (IEF) showed that the ratio of apo E/C or apo C-II/C-III in VLDL was markedly decreased and the ratio of apo E or apo C to apo A1 in high-density lipoprotein (HDL) was slightly decreased in DS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An autopsy case of Alzheimer disease with myoclonus and periodic spikes on EEG.

This is a case of Alzheimer disease with myoclonus and periodic spikes on EEG. A 56-year-old man developed progressive dementia and, 3 years later, generalized convulsions. Eight years later, he showed myoclonus and periodic spikes on EEG. Cranial CT showed cortical atrophy and ventricular dilatation. He became apallic and died of pneumonia at the age of 65.9 years after the onset of the disease. The brain weighed 1,050 g. Neuropathologically, diffuse neuronal loss, abundant neurofibrillary tangles and senile plaques, particularly diffuse plaques, were found extensively in the cerebral cortex. The white matter was preserved. In the Ammon's horn, abundant neurofibrillary tangles and senile plaques were observed. Grumose degeneration of the cerebellar dentate nucleus, Kuru plaques or prions were not found. Numerous diffuse plaques of the cerebral cortex have rarely been reported in autopsy cases of Alzheimer disease with myoclonus and periodic spikes on EEG.

Alzheimer Disease↗

Fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, suppresses very low-density lipoprotein secretion in puromycin aminonucleoside-nephrotic rats.

The effects of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the hyperlipidemia associated with nephrosis were studied. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma triglyceride (TG), total cholesterol and apoprotein (apo) B concentrations than controls. Fluvastatin was administrated as a 0.01% solution in drinking water for 14 days to either normal control or nephrotic rats. Concentrations of TG and apo B in plasma, and very low-density lipoprotein (VLDL) in nephrosis were completely normalized by the treatment with fluvastatin, but concentrations of cholesterol in plasma and each lipoprotein fraction were not altered by the treatment. The ratio of apo E to C in VLDL was significantly decreased in nephrotic rats, but the fluvastatin treatment increased this ratio. TG secretion rate estimated by the Triton WR1339 method was significantly increased in nephrotic rats, but was normalized by fluvastatin. Percent composition of TG in newly secreted VLDL particles in post-Triton plasma was not decreased by fluvastatin treatment, suggesting that the number of newly secreted VLDL particles was reduced by the treatment. Postheparin plasma lipolytic activities were not affected by the fluvastatin treatment. These results demonstrate that fluvastatin can effectively ameliorate the high concentration of VLDL by suppressing the hepatic secretion in nephrotic rats, and suggest that an inhibition of cholesterol biosynthesis suppresses VLDL secretion from the liver.

Animals↗

Stress increases the secretory product of rat nasal mucosa goblet cells.

The effect of stress on the secretory activity of rat nasal mucosa goblet cells was examined by quantitative histochemistry. Mucosa was prepared from the nasal septum of male rats with or without electric shock applied to the tail. Mucosa was fixed with formaldehyde and stained with alcian blue. The epithelial layer was further dissected, and examined microscopically. The percentage of stained area was estimated with the aid of a microscope connected to a computerized video system. The stained area, which corresponded to the secretory granules of mucosal goblet cells, was greater in the electrically shocked group than the control group. This result raises the possibility that stress enhances the secretory activity of goblet cells in nasal mucosa.

Alcian Blue↗

[A case report of concurrent esophageal and gastric double cancer successfully treated by surgery and the effectiveness of the oral administration of polyacrylate pasta (PANA kayaku) and bleomycin oil in esophageal carcinoma].

The patient was a 65-year-old male who came to our hospital with a complaint of dysphagia. He was admitted to hospital following a diagnosis of combined tumor in the esophagus and stomach as revealed by X-ray fluoroscopy. For preoperative chemotherapy, he was given oral administration of BLM-polyacrylate pasta, 30 mg/day for 25 days and 15 mg/day for 5 days, up to a total dose of 825 mg. This regimen successfully reduced the tumor in the esophageal area. No signs of pulmonary dysfunction, changes in blood cell count and blood chemistry of any other abnormalities in his general status were seen as side-effects of the BLM-polyacrylate pasta. Thoracic-esophagectomy and total gastrectomy were performed on November 7, 1983. He has been maintaining a good quality of life without any signs of recurrence of the tumor for the last two years and six months after the operation. The esophageal tumor was identified as moderately differentiated squamous cell carcinoma with A0N0M0Pl0 and grade of invasion "mp", while the gastric tumor was moderately differentiated adenocarcinoma with H0P0S0N0 and invasion grade "m" in the early stage of IIa + IIc type.

Acrylic Resins↗

Clinical and biochemical effects of calcium-hopantenate on neuroleptics-induced tardive dyskinesia.

Calcium-hopantenate (HOPA), a derivative of GABA, was administered to 9 psychiatric patients with neuroleptics-induced tardive dyskinesia. In a clinical study, involuntary movements have improved significantly after a 4-8-week medication. Although there was no correlation between the cerebrospinal fluid (CSF) levels of HOPA, GABA, HVA or clinical response, the CSF HOPA levels significantly correlated with changes in the CSF GABA levels. These results suggest that HOPA alleviates the symptoms of tardive dyskinesia being mediated by the central GABAergic mechanisms.

Adult↗

Possible relationship between antimanic effect and activity of zotepine to 5HT1 receptor.

Zotepine (ZTP), synthesized by Fujisawa Pharmaceutical Co., Ltd. for possible use as an antipsychotic drug, clinically features a very rapid and potent antimanic effect. To elucidate the psychopharmacological mechanisms of zotepine, we have attempted to measure the potency of ZTP compared with other neuroleptic drugs in competing for binding sites in the brain associated with dopamine, serotonin (5-HT1, 5-HT2), noradrenaline (NA) and acetylcholine. Zotepine was found to have the most potent activity to the 5HT1 receptor among the test drugs. Chlorpromazine and thioridazine, which belong to phenothiazines and clinically have less potent antimanic effect, shared ZTP's potent activity to the NA receptor, while they were less potent than ZTP in activity to the 5HT1 receptor. These results show that the activity of the drugs to the 5HT1 receptor may be associated with the antimanic effect.

Animals↗

CSF monoamine metabolism in patients with tardive dyskinesia: effect of oxypertine and hydroxyzine pamoate.

Cerebrospinal fluid (CSF) HVA, MHPG, 5-HIAA, cAMP and cGMP concentrations were measured in schizophrenic patients with tardive dyskinesia before and after a three-week administration of oxypertine (n = 4), hydroxyzine pamoate (n = 4) or placebo (n = 4). The oxypertine administration resulted in a reduction of the CSF HVA concentration and an elevation of the MHPG and cAMP concentrations, associated with a clinical improvement in tardive dyskinesia. The hydroxyzine administration reduced the CSF 5-HIAA concentration in all the patients and the CSF HVA concentration in two of four patients with a clinical improvement. A reduction in the CSF HVA concentration associated with possible therapeutic effects of oxypertine or hydroxyzine may suggest the normalization of a hyperdopaminergic state. Discussions were held that functional disorders of not only the dopaminergic system but the norepinephrinergic and serotoninergic systems may relate to the pathogenesis of tardive dyskinesia.

Biogenic Amines↗

Cerebrospinal fluid monoamine metabolites during alcohol withdrawal syndrome and recovered state.

The aim of the study was to examine changes in cerebrospinal fluid (CSF) monoamine concentrations related to alcohol withdrawal. Lumbar puncture was performed in 8 healthy volunteers (control group) and 36 chronic alcoholic patients following alcohol withdrawal. A second lumbar puncture was performed in 20 of these patients after recovery from the withdrawal. CSF 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) were measured. Alcohol withdrawal phenomena in all patients were classified in the following three groups: (i) major withdrawal syndrome: alcohol-withdrawal delirium, (ii) minor withdrawal syndrome: evident autonomic nervous hyperactivity without hallucination or clouding of consciousness, and (iii) asymptomatic type: a withdrawal period without overt symptoms. MHPG concentration was significantly increased in the major withdrawal syndrome, as compared with other groups, including the controls. No change in MHPG was found in the patients without overt autonomic nervous syndrome. A positive correlation between CSF-MHPG and intensity of withdrawal symptoms (r = 0.60, p less than 0.02) was found. A higher correlation between CSF-MHPG and intensity of autonomic nervous disturbances was also found (r = 0.86, p less than 0.001). CSF-HVA was significantly low during the alcohol delirium. It is suggested that a close relationship may exist between autonomic nervous disturbances and increase in central noradrenergic activity, as well as between the alcohol delirium and decrease in central dopaminergic activity.

Adolescent↗

Effects of lithium on rat tail nerve conduction velocity.

Orthodromic and antidromic conduction velocities were measured in the tail nerve of rats given lithium throughout life. Lithium at nontoxic levels failed to influence nerve conduction velocities. Lithium at toxic levels (2 X 2.5 mmol/kg/day for 7 days) produced overt signs of lithium intoxication and reduced both orthodromic and antidromic nerve conduction velocities. The reductions in conduction velocities were related inversely to the level of lithium in serum and red blood cells. Conduction velocities returned to normal levels after cessation of the toxic lithium treatment. The findings show life-long administration of lithium at nontoxic levels to be without adverse effects on peripheral nerves in rats, while toxic lithium levels caused reversible impairment in conduction properties in peripheral nerves.

Animals↗