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Biomedical subjects

Y Umeda

Publications and source records attributed to Y Umeda.

At least 109 records · Page 6Linked to original sources

Role of atrial natriuretic polypeptides for exaggerated natriuresis in essential hypertension.

Eighteen patients with essential hypertension were separated into 2 groups, renin-unresponsive and renin-responsive, on the basis of their plasma renin response when challenged by furosemide and upright posture. The response to acute infusion of hypertonic saline solution (1.4% saline solution at a rate of 0.3 ml/min/kg over 60 minutes) was then studied. In the renin-unresponsive group, peak rate of fractional excretion of sodium and peak urine flow after saline loading were 7.6 +/- 0.7% and 476 +/- 34 ml/hour, respectively, and peak value of atrial natriuretic polypeptides (ANP) was 784 +/- 140 pg/ml. In the renin-responsive group, the values were 3.1 +/- 0.4%, 194 +/- 29 ml/hour and 115 +/- 33 pg/ml. Both fractional excretion of sodium, urine flow and ANP response were significantly higher (p less than 0.01) in the renin-unresponsive group. Moreover, a highly significant relation (r = 0.82, p less than 0.01) was observed between fractional excretion of sodium and ANP levels in all hypertensive patients. The degree of saline-induced natriuresis was not related to blood pressure, heart rate, endogenous creatinine clearance, antidiuretic hormone or preexisting level of aldosterone. Plasma renin activity changed little in either group during saline infusion, but tended to be higher at all times in the renin-responsive patients. The present findings suggest that the enhanced secretion of ANP is an important determinant for exaggerated natriuresis observed in patients with renin-unresponsive hypertension.

Adult↗

Inhibition of gastric acid secretion by human calcitonin gene-related peptide with picomolar potency in guinea-pig parietal cell preparations.

The effect of CGRP on [14C]-aminopyrine accumulation in isolated parietal cell preparations from guinea-pig fundic mucosa was studied. Parietal cells consisted of 60% of the preparations. [14C]-Aminopyrine accumulation was used as an index of physiological response of parietal cells to secretagogues. CGRP dose-dependently (10(-12)-10(-9) M) inhibited parietal cell aminopyrine accumulation stimulated by histamine (10(-4) M), carbachol (10(-4) M), and pentagastrin (5 X 10(-6) M). The concentration of CGRP exerting half-maximal inhibition of [14C]-aminopyrine accumulation was 8.7 X 10(-11) M for histamine, 9.1 X 10(-11) M for carbachol, and 4.7 X 10(-11) M for pentagastrin. The inhibitory effect was much more potent than cimetidine, pirenzepine or benzotript. CGRP but not cimetidine inhibited DBcAMP stimulated aminopyrine accumulation (IC50 = 7.5 X 10(-11) M). These results suggest that CGRP may exert its inhibitory action on gastric acid secretion by a direct action on the parietal cell or the somatostatin-producing D cell.

Aminopyrine↗

Effects of steroid and thyroid hormones on synthesis of atrial natriuretic peptide by cultured atrial myocytes of rat.

The in vitro effects of various steroid and thyroid hormones on synthesis of rat atrial natriuretic peptide (rANP) were studied using new-born rat atrial myocytes in culture. Dexamethasone, testosterone and triiodothyronine markedly stimulated both synthesis and secretion of immunoreactive (IR)-rANP with the same peak after 4-day-culture. Dexamethasone and testosterone dose-dependently (10(-7)-10(-6) M) stimulated synthesis of IR-rANP and were the most potent among various steroids tested. Triiodothyronine (T3) also stimulated synthesis of IR-rANP in a dose-dependent manner (10(-8)-10(-7) M), of which effect was more potent than that of tetraiodothyronine, whereas reverse T3 was ineffective. The present study clearly shows that glucocorticoids, androgens and thyroid hormones directly stimulate synthesis of ANP by atrial myocytes and suggests that ANP may play a potential role in mediating and/or modulating the biological effects by these hormones in the cardiovascular system.

Adrenal Cortex Hormones↗

The role of atrial pressure in secreting atrial natriuretic polypeptides.

The role of atrial pressure and catecholamines in secreting human atrial natriuretic polypeptides (hANP) were investigated in patients with acute or old myocardial infarction (AMI or OMI). No differences were observed in hANP levels obtained from brachial vein, right atrium, pulmonary artery and femoral artery, suggesting that hANP degradation in the pulmonary circulation has little clinical significance in hANP measurement. Plasma hANP levels in 10 patients with AMI were higher than those in controls and significantly correlated to both mean right atrial pressure (mRA) and pulmonary wedge pressure (PCW) (r = 0.76, p less than 0.05; r = 0.95; p less than 0.01, respectively). In 12 patients with OMI, plasma hANP levels were normal at rest and were significantly increased (p less than 0.01) with bicycle ergometer exercise associated with significant elevations of plasma catecholamine levels, mRA, and PCW. However, the increments of hANP correlated only to those of PCW. These results suggest that the elevation of atrial (principally left atrial) pressure rather than catecholamine stimulates hANP secretion.

Aged↗

[Surfer's ear].

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Adolescent↗

Synthesis and antitumor activity of spergualin analogues. II. Chemical modification of the spermidine moiety.

Chemical modifications of the spermidine moiety of an antitumor antibiotic, spergualin (Ia), and the structure-activity relationship are described. Replacement of spermidine with other polyamines decreased the antitumor activity against mouse leukemia L1210. Analogues containing an oxidized spermidine moiety that probably formed during oxidation with amine oxidase were inactive. Spermidine is indispensable for the antitumor activity. A facile method for the synthesis of glyoxyloyl polyamine, a key intermediate of spergualin-related compounds, is also reported.

Animals↗

Synthesis and antitumor activity of spergualin analogues. III. Novel method for synthesis of optically active 15-deoxyspergualin and 15-deoxy-11-O-methylspergualin.

Optically active 15-deoxyspergualin (II) and 15-deoxy-11-O-methylspergualin (IIa) were synthesized, and their antitumor activities were examined. The (-)-enantiomers of both II and IIa were active against mouse leukemia L1210, while the (+)-enantiomers were almost inactive. The optical resolution of the key intermediate, (+/-)-N-(7-guanidinoheptanoyl)-alpha-alkoxyglycine (VI) was achieved by use of an exopeptidase, serine (acid) carboxypeptidase [EC 3.4.16.1] and (+/-)-N-(7-guanidinoheptanoyl)-alpha-alkoxyglycyl-L-amino acid (VIII) as the substrate. Considering the enzymatic susceptibility of the substrate (VIII), we deduced that the absolute configuration of the carbon at 11 (C-11) of the bioactive (-)-enantiomer, and so that of natural spergualin (I), is S. This is, to our knowledge, the first report of the use of carboxypeptidase for the resolution of N-acyl amino acid.

Animals↗

An autopsy case of chronic nodular encephalomyelitis simulating neuro-Behçet syndrome.

A 29-year-old man suffered from neurological symptoms such as urinary disturbance, changes in personality, gait and speech disturbances, amnesia, myoclonus, dysphagia and muscle atrophy for nine years with exacerbations and remissions. A postmortem examination revealed many inflammatory and necrotic foci in the brain and spinal cord, especially in the brainstem and cerebral cortex. Numerous minute scar foci were also scattered in the gray matter, accompanied by some demyelinating lesions in the white matter. The presence of microthrombi and plasma exudation into the vessel wall suggested the importance of vascular factors in the pathogenesis of these CNS lesions. Peripheral neuropathy was also present. The neuropathological features were almost the same as those of neuro-Behçet syndrome, but he lacked the extraneural symptoms of Behçet disease.

Adult↗

Effects of trimoprostil on healing and recurrence of acetic acid-induced gastric ulcer in rats.

Chronic gastric ulcers were produced by injection of 20% acetic acid (0.05 ml) into the submucosal layer of the rat stomach in order to determine the effects of the prostanoid trimoprostil on the healing and recurrence of ulcers. Local injection of acetic acid solution produced large demarcated ulcers in all animals on day 5, which rapidly decreased to reach low levels on days 40-80 and then became exacerbated on day 100. The exacerbation of the ulcer is probably recurrence. Trimoprostil was administered ad libitum in drinking water containing 0.1, 0.3 and 1.0 microgram/ml (average dose 12.4, 37 and 124 micrograms/kg/day) for a period of 14 days (day 1-15) to assess its effect on healing and for a period of 40 days (day 60-100) to assess its ability to prevent recurrence. The higher two doses of trimoprostil accelerated the spontaneous healing of the ulcers. Furthermore, trimoprostil, at both doses, prevented the observed recurrence of this type of ulcer. Trimoprostil dose-dependently (30-300 micrograms/kg, p.o.) inhibited gastric secretion in pylorus-ligated rats. Cimetidine at the antisecretory dose (1 mg/ml, 132 mg/kg/day) failed to affect the healing process of gastric ulcers, but tended to prevent the recurrence of gastric ulcers. Our present study suggests that trimoprostil is a promising antiulcer drug for the treatment of chronic gastric ulcer.

Acetates↗

Enhanced vasopressin release upon activation of the central neural mechanism in spontaneously hypertensive rats.

Monopolar electrical stimulation of the intermediate portion of the solitary nucleus in spontaneously hypertensive rats (SHRs) with cervical cordotomy and vagotomy resulted in a 1.68 times greater increase in plasma vasopressin concentration than in Wistar rats. The result implies that such an enhanced function of the central neural mechanism to release vasopressin in SHR backs up the functionally aberrant cardiovascular receptors.

Animals↗

Approach for quantifying the overall function of the ascending central neural integration to release vasopressin in rats.

Electrical stimulation of the intermediate portion of the solitary nucleus (SOL) is known to consistently elicit a pressor response and increase in the release of vasopressin (VP) in rats, when the cervical spinal cord and vago-sympathetic trunks are cut. The aim of the present study was to provide a methodological assessment for this technique, in order to quantify the central neuroendocrine function to release VP. Experiments were conducted on rats with cervical cordotomy and vagotomy, under 60% N2O anesthesia and artificial ventilation. The animals were maintained at their normal arterial blood pressure by infusing phenylephrine, which itself exerted little influence on the arterial plasma VP concentration (pVP) during SOL stimulation. In order to prevent blood loss, cross circulation with a donor rat was utilized in the blood sampling for pVP determination. We confirmed that this technique itself did not significantly affect the pVP level. A monopolar stimulus at a frequency of 50 Hz was found to produce the pressor response most effectively. The current spread of the stimulation (0.5 ms duration; 1 s on/1 s off; up to at least 120 microA) did not induce a false-positive pressor response mediated by other structures adjacent to the SOL. We suggest that electrical stimulation of the SOL in rats with cervical cordotomy and vagotomy, for observing the pressor response and/or increase of pVP, represents a rapid approach for screening the overall function of the ascending efferent part of the reflex mechanisms to release VP.

Animals↗

Synthesis and antitumor activity of spergualin analogues. I. Chemical modification of 7-guanidino-3-hydroxyacyl moiety.

Many analogues and derivatives of an antitumor antibiotic, spergualin, were synthesized, and the relationships between the structure and the activity against mouse L-1210 tumor were studied. Both modification of the 15-hydroxyl group and alteration of chain-length of the omega-guanidinoacyl moiety affected the activity. 15-Deoxyspergualin (18, 1-amino-19-guanidino-11-hydroxy-4,9,12-triazanonadecane-10,13-d ion e) and its analogue 25 (1-amino-21-guanidino-11-hydroxy-4,9,12-triazauneicosane-10,13-dio ne) had strong activity, superior to that of spergualin.

Animals↗

Release of vasopressin by electrical stimulation of the intermediate portion of the nucleus of the tractus solitarius in rats with cervical spinal cordotomy and vagotomy.

The cervical spinal cord and vagi were severed in anesthetized and artificially ventilated rats. Monopolar electrical stimulation of the intermediate portion of the nucleus of the tractus solitarius (NTS) resulted in subtle increases in concentration of plasma vasopressin (pVP) and in arterial pressure. We suggest that electrical stimulation of the NTS in rats undergoing such surgical preparation to observe the pressor response and/or increase in pVP, represents a rapid approach for screening the neurosecretory function of the central neural integration to release vasopressin.

Animals↗