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Biomedical subjects

A Goto

Publications and source records attributed to A Goto.

At least 163 records · Page 9Linked to original sources
PubMed1994

Antihypertensive property and renal protection by shichimotsu-koka-to extract in salt-induced hypertension in Dahl strain rats.

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsukoka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Animals↗
PubMed1994

Role of ouabainlike compound in rats with reduced renal mass-saline hypertension.

Ouabainlike compound (OLC) has recently been identified as a likely mammalian endogenous digitalis-like factor (EDLF) from human plasma. In this study, plasma levels of OLC were determined to assess the role of OLC in a model known as volume-expanded, reduced renal mass (RRM)-saline (S) hypertension in rats with use of a newly developed radioimmunoassay for ouabain. In the first experiment, at 3 wk after subtotal nephrectomy and drinking 1% saline solution, sysolic blood pressure (SBP) of 18 rats with reduced renal mass (RRM-S rats) was significantly higher than in 17 sham-operated saline-drinking control (C-S) rats [154 +/- 4 (SE) vs. 132 +/- 2 mmHg; P < 0.01]. Plasma OLC levels were 355 +/- 68 pmol/l in RRM-S rats, sevenfold higher than in C-S rats (54 +/- 4 pmol/l; P < 0.01). In the second experiment, we measured plasma OLC levels of 10 RRM-S, 12 sham-operated control (C), and 10 subtotally nephrectomized rats drinking distilled water (RRM rats). Concomitant with a marked increase in blood pressure (203 +/- 5 mmHg), RRM-S rats showed significantly higher plasma OLC levels compared with C and RRM rats (RRM-S 114 +/- 24, C 47 +/- 11, and RRM 52 +/- 9 pmol/l; P < 0.05). In both experiments, plasma OLC levels correlated significantly with SBP (P < 0.05). These findings suggest that plasma OLC shows a similar behavior to that of EDLFs or Na(+)-K(+)-adenosinetriphosphatase inhibitors reported in previous publications and may play a role in hypertensive mechanisms in rats with RRM and excess Na intake.

Animals↗
PubMed1994

Participation of ouabainlike compound in reduced renal mass-saline hypertension.

We examined the role of ouabainlike compound in reduced renal mass-saline hypertension using a population of rats immunized with ouabain. To develop ouabain-immunized rats, ouabain-bovine serum albumin conjugates were injected subcutaneously three times at 4-week intervals. Titer determinations were made 2 weeks after the third immunization, and rats with high titers were used in the study. Immunoglobulin G fractions from ouabain-immunized rats effectively inhibited the contractile response of guinea pig aorta to exogenous ouabain (150 nmol). Fourteen ouabain-immunized and seven nonimmunized control rats underwent subtotal nephrectomy. An additional eight ouabain-immunized and six nonimmunized rats served as sham-operated rats. Four groups of rats drank 1% NaCl solution for 3 weeks, and systolic blood pressure was measured weekly by the tail-cuff method. Two groups of sham-operated rats remained normotensive. In contrast, two groups of subtotally nephrectomized rats developed hypertension. However, among these rats, systolic blood pressure was significantly lower in ouabain-immunized rats than in nonimmunized rats (161 +/- 5 versus 180 +/- 3 [+/- SEM) mm Hg, P < .01). The decrease in blood pressure was accompanied by a significant inhibition of aortic hypertrophy (P < .05). These results indicate that chronic blockade of circulating ouabainlike compound partly ameliorates reduced renal mass-saline hypertension and suggest that circulating ouabainlike compound may be involved in the pathophysiology in this model of hypertension.

Adrenal Glands↗
PubMed1994

Role of brain ouabainlike compound in central nervous system-mediated natriuresis in rats.

Intracerebroventricular infusion of artificial sodium-rich cerebrospinal fluid induces increases in blood pressure and urinary sodium excretion. To examine the role of brain ouabainlike compound in these central nervous system-mediated responses, we evaluated the effects of prior intracerebroventricular injection of the Fab fragments of digoxin-specific antibody (Digibind, 10 mg/mL, 10 microL) on changes in blood pressure and urinary sodium excretion after intracerebroventricular infusion of high-sodium (323 mmol/L, 150 microL/kg per 15 minutes) cerebrospinal fluid in anesthetized rats. Antiouabain action of Digibind was revealed by the inhibition of a contractile response to ouabain in guinea pig aorta. Similar significant increases in blood pressure were found in rats that received preinjection of Digibind (n = 14) compared with control rats that received injection of saline (n = 5) or normal sheep IgG (n = 8). In rats pretreated with Digibind the natriuretic responses to central high sodium were significantly diminished by 68% (P < .05) or 82% (P < .05) compared with rats treated with saline or normal IgG, respectively. In contrast, Digibind did not affect either pressor or natriuretic responses to intracerebroventricular angiotensin II (600 ng/30 microL per 10 minutes). These data indicate that Digibind significantly inhibits increases in renal sodium excretion in response to high central sodium and suggest that brain ouabainlike compound may be involved in central nervous system-mediated natriuresis with nonpressor mechanisms.

Animals↗
PubMed1994

Long-term infusion of kallikrein attenuates renal injury in Dahl salt-sensitive rats.

We investigated whether long-term infusion of kallikrein would attenuate renal injury in salt-induced hypertension in Dahl salt-sensitive rats. A subdepressor dose of purified rat urinary kallikrein (700 ng/d IV) was infused by osmotic minipump for 4 weeks in male Dahl salt-sensitive rats fed a high salt (2% NaCl) diet. This dose did not affect the time-dependent elevation of blood pressure; however, urinary protein excretion was significantly decreased, and glomerular filtration rate was increased. These beneficial effects were reflected morphologically by an attenuation of glomerulosclerotic lesions and tubular injury seen in the hypertensive Dahl salt-sensitive rats. Kallikrein infusion increased urinary excretion of bradykinin and stimulated excretion of cyclic GMP, suggesting that the kallikrein-kinin-prostaglandin and nitric oxide axes were enhanced by rat urinary kallikrein infusion. The alterations induced by kallikrein infusion were potentiated by the concomitant administration of the angiotensin-converting enzyme inhibitor alacepril. These studies indicated that long-term replacement with rat tissue kallikrein attenuates renal injury in hypertensive Dahl salt-sensitive rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

A preterm infant with secondary carnitine deficiency due to MCT formula--effective treatment of L-carnitine.

We report a preterm infant who was prescribed an MCT formula and subsequently developed carnitine deficiency with liver dysfunction and an elevation of serum CK level. A male infant who had been born at 24 weeks' gestation with birth weight 799 g, was fed with an MCT formula containing 76.8% of all kinds of lipids, because of his steatorrhea after the 30th day. On the 100th day, he was noted hepatomegaly and elevation of serum levels of AST, ALT and CK. The needle biopsy of the liver indicated the existence of the liver damage. He showed low serum carnitine with high urinary loss of acylcarnitine and dicarboxylic aciduria. Administration of L-carnitine was an effective treatment. The carnitine deficiency might be exaggerated by an increased urinary loss of acylcarnitine. We should be cautious of the risk of carnitine deficiency in preterm infants during prolonged use of MCT formula.

Carnitine↗
PubMed1994

Mechanistic analysis of renal protection by angiotensin converting enzyme inhibitor in Dahl salt-sensitive rats.

OBJECTIVE: To investigate whether and how renin-angiotensin inhibition attenuates renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl-S) rats. METHODS: Dahl-S rats fed a high-salt (4% sodium chloride) diet for 6 weeks were treated with the angiotensin converting enzyme (ACE) inhibitor alacepril or the angiotensin receptor antagonist losartan for 4 weeks. Functional and morphological alterations in the kidney were investigated. RESULTS: Alacepril decreased systolic blood pressure (SBP). This SBP reduction was associated with the attenuation of cardiac and aortic wall hypertrophy and that of proteinuria and urinary N-acetyl-beta-D-glucosaminidase excretion. Kidney injuries, e.g. glomerular, arterial and tubular damage, were improved with alacepril treatment. Losartan decreased SBP to the same extent as alacepril, but neither renal function nor morphological structure was improved as was the case with alacepril. The response of the renal eicosanoid system to alacepril was inadequate, but cyclic GMP excretion, an indicator of nitric oxide formation, was significantly enhanced and lipid peroxidation in the kidney was decreased. CONCLUSIONS: The beneficial effects of ACE inhibition on the renal injury in Dahl-S rats outrange those induced by the receptor antagonism. This might be due to multiple factors including an increased vasodepressor eicosanoid system, enhanced nitric oxide formation and possible inhibition of oxygen radical generation in the injured renal tissues.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Effects of a calcium antagonist and an angiotensin II receptor antagonist on rat renal arterioles.

The objective of this study was to investigate the effects of a dihydropyridine calcium antagonist, manidipine HCl, and an angiotensin II receptor antagonist, CV-11974, on renal microvasculature in hypertensive rats. Hydronephrosis was induced by ligation of the left ureter in 8-week-old stroke-prone spontaneously hypertensive rats. Two months after the operation, the hydronephrotic kidney was split longitudinally and spread out as a thin sheet, and the renal microvasculature was observed directly under a light microscope. Administration of manidipine HCl (20 micrograms/kg) caused a gradual fall in blood pressure (-34 mmHg). The afferent arterioles were dilated, and maintained the same level of dilatation until 30 min (+20%). The efferent arterioles were also dilated (+8%). Glomerular blood flow was significantly increased (+38%). Administration of CV-11974 (100 micrograms/kg) caused a sharp fall in blood pressure at 2 min (-24 mmHg), with a continuous fall in blood pressure until 60 min (-46 mmHg). The afferent arterioles were gradually dilated (+15%). The efferent arteriole was also dilated until 60 min, but to a lesser extent than the afferent arteriole. Glomerular blood flow was immediately increased (+35%). We conclude that both manidipine HCl and CV-11974 dilated both the afferent and efferent arterioles and increased glomerular blood flow.

Angiotensin Receptor Antagonists↗
PubMed1994

Mechanisms underlying the augmented responses of deoxycorticosterone acetate-salt hypertensive rats to neutral endopeptidase inhibitors.

OBJECTIVE: To explore the mechanisms for augmented neutral endopeptidase inhibitor-induced natriuresis in deoxycorticosterone acetate (DOCA)-salt rats. METHODS: We examined effects of a neutral endopeptidase-inhibitor, candoxatril, on plasma and urinary brain natriuretic peptide (BNP) levels, the influence of a specific atrial natriuretic peptide (ANP) receptor antagonist, HS-142-1, on the response to candoxatril, and the renal neutral endopeptidase activity in DOCA-salt rats. RESULTS: Candoxatril decreased blood pressure and increased urinary sodium excretion, both of which were greater in DOCA-salt rats than in normotensive control rats. These effects were associated with a significant rise in the plasma BNP level and the plasma ANP level in DOCA-salt rats. Urinary ANP excretion also increased, but urinary BNP excretion was not changed by candoxatril. Pretreatment with a specific ANP receptor antagonist (HS-142-1) diminished the effect of candoxatril on urinary sodium excretion, blood pressure and urinary cyclic GMP excretion. Urinary neutral endopeptidase-like activity was greater in DOCA-salt rats than in control rats. Northern blot analysis revealed that the ratio of renal neutral endopeptidase messenger RNA (mRNA) to beta-actin mRNA was comparable between the two groups. CONCLUSIONS: The neutral endopeptide inhibitor exerted its hypotensive and natriuretic effects mainly via the potentiation of the endogenous natriuretic peptides, including BNP. The augmented response of DOCA-salt rats also seems to be mediated by both the downregulation of clearance receptors and an increase in renal neutral endopeptidase activity.

Animals↗
PubMed1994

[Efficacy of combination therapy against MRSA in Ibaraki Prefecture].

Clinical efficacies of fosfomycin (FOM) or arbekacin (ABK) plus beta-lactam combination therapies against methicillin-resistant Staphylococcus aureus (MRSA) infections were examined in 15 major hospitals in Ibaraki Prefecture. The subjects were 54 inpatients from January 1991 to April 1993, and most of them showed moderate to severe infections with underlying diseases. MRSA alone was isolated from 23 patients and the other 31 patients had polymicobes including MRSA. Pseudomonas aeruginosa was the most frequent among the co-isolated strains. The number of patients treated with FOM and cefmetazole (CMZ) was 22 (Group C) and that with FOM and flomoxef (FMOX) was 25 (Group F). CMZ or FMOX was administrated 60 minutes after FOM administration. To 8 nonresponding patients in Groups C and F and 7 nonresponders to the other therapies, ABK and ceftazidime (CAZ) or ABK and piperacillin (PIPC) were treated simultaneously (Group A). The clinical efficacies of Groups C and F were 63.6% and 64%, respectively. The bacteriological efficacies (eradication rates) of both groups including microbial substitutions were 42.9% in the former and 56.5% in the latter. No statistical differences were observed in the clinical and the bacteriological efficacies between Groups C and F. The clinical and bacteriological efficacies in Group A were 66.7% and 46.2%, respectively. No side effects were observed in any cases. Mild disturbances of hepatic functions were observed in 2 cases of Groups C and F, and there were no abnormal laboratory test results in Group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

A case of polypoid cavernous hemangioma of the sigmoid colon excised by colonoscopic polypectomy.

A 28-year-old Japanese man was admitted to our institute because of sharp anal pain and a mass that prolapsed from the anus after defecation. After spinal anesthesia for emergency operation, the mass spontaneously withdrew into the anus and the pain disappeared. Surgery was postponed. Barium enema and colonoscopy revealed a pedunculated polyp in the sigmoid colon, which was removed by snare polypectomy with electrocautery. The resected polyp was granular and reddish, and measured 33 x 22 x 14 mm. Histological examination of the polyp revealed a cavernous hemangioma. Hemangioma of the colon is rare; only 52 cases have been reported in Japan. Of these patients, eight underwent endoscopic polypectomy. The present lesion is the largest thus treated that has been documented. Endoscopic polypectomy seems to be a safe and preferable procedure for the diagnosis and treatment of small, solitary polypoid hemangiomas of the colon.

Adult↗
PubMed1993

Digitalis-like factors from human urine.

We isolated two candidates for endogenous digitalis-like factors from human urine based on the inhibition of [3H]ouabain binding to intact human erythrocytes. The more-polar ouabain-displacing compound-1 (ODC-1) closely resembled ouabain in biological, physicochemical, and chromatographic properties. Moreover, anti-ouabain IgG dose-dependently neutralized the action of ODC-1. The less-polar ODC-2 behaved identically to digoxin in three analytical high-performance liquid chromatography and thin layer chromatography systems. Fast atom bombardment mass spectrum and proton nuclear magnetic resonance spectrum supported the notion that ODC-2 may be indistinguishable from digoxin. The possibility that substances quite similar to cardenolides are synthesized in the mammalian body must be seriously considered.

Binding Sites↗
PubMed1993

Effects of BMY-21502 on anoxia in mice.

The protective effects of BMY-21502 (1-[[1-[2-(trifluoromethyl)-4-pyrimidinyl]-4-piperidinyl]methyl]-2- pyrrolidinone) against cerebral anoxia were investigated using various models in mice, in comparison with those of other cerebroactive drugs. Oral administration of BMY-21502 (10-100 mg/kg) significantly prolonged the survival time in KCN (2.4 mg/kg, i.v.)-induced anoxia. Oxiracetam and idebenone exerted similar but weak protection at doses above 100 mg/kg, p.o. and only at a dose of 100 mg/kg, p.o., respectively. Significant protection by BMY-21502 against moderate hypobaric hypoxia was observed at doses of 30 and 100 mg/kg, p.o. Idebenone (100 and 300 mg/kg, p.o.) significantly prolonged the survival time of mice in this model, but oxiracetam (30-300 mg/kg, p.o.) did not. Oral administration of all of these drugs (BMY-21502, 3-300 mg/kg; Oxiracetam, 100-1000 mg/kg; Idebenone, 100-1000 mg/kg) failed to increase the number of gasps and the duration of gasping in the decapitated head of mice as a complete ischemic model. The anti-anoxic effect of BMY-21502 in the KCN-anoxia model was blocked by pretreatment with scopolamine. These findings suggest that BMY-21502 has an anti-anoxic action superior to those of the other cerebroactive drugs used, and activation of the CNS cholinergic system is involved as one of the causative mechanisms for the anti-anoxic effect of BMY-21502.

Animals↗
PubMed1993

Comparison of the anticonflict effect of buspirone and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in rats.

The anxiolytic effects of buspirone and its major metabolite, 1-(2-pyrimidinyl)-piperazine (1-PP) have been investigated with a conflict (shock-induced suppression of drinking) paradigm in rats. Buspirone (10 mg/kg, p.o.) showed an anticonflict activity with a bell-shaped dose-response relationship without any effect on spontaneous water consumption. Higher doses of buspirone reduced the punished response. Diazepam (20 and 40 mg/kg, p.o.) also showed an anticonflict activity in a dose-dependent manner, but animals with diazepam showed an increase in spontaneous water consumption at these doses. On the other hand, 1-PP (6.25-200 mg/kg, p.o.) showed a weak anticonflict activity with a significant effect at 25 mg/kg without any effect on spontaneous water consumption. In the 7-day treatment test, buspirone (5 and 10 mg/kg, p.o.), 1-PP (5 and 25 mg/kg, p.o.) and diazepam (10 and 40 mg/kg, p.o.) did not develop the tolerance to the anticonflict activity. Conversely, the anticonflict activity of diazepam was increased by the repeated treatment. Diazepam (10 mg/kg, p.o.) showed an anticonflict activity without any effect on spontaneous water consumption in this test. These results demonstrated that buspirone clearly exhibited an anticonflict effect similar to that of diazepam in a Vogel-type conflict test, and its real anxiolytic effect may not be always based on 1-PP, the main metabolite of buspirone.

Animals↗
PubMed1993

Encapsulation of chicken egg yolk immunoglobulin G (IgY) by liposomes.

Encapsulation of antibodies isolated from chicken egg yolk (IgY) in egg lecithin/cholesterol liposomes was attempted. IgY was successfully encapsulated into the liposomes by using the dehydration-rehydration method. Electron microscopic observation demonstrated that the liposomes prepared by this method were large multilamellar vesicles with a diameter of several microns. The encapsulation efficiency was improved by increasing the rehydration temperature to 60 degrees C. The cholesterol/lecithin ratio also affected the efficiency, giving the highest value at a ratio of 1/4 (mol/mol). Some efflux of glucose through the liposomal membranes was observed, particularly for the liposome with a low cholesterol content, but that of IgY was not detected, irrespective of the cholesterol content. Encapsulation reduced the activity loss of the IgY antibodies under acidic conditions. IgY encapsulated in the liposomes was also markedly resistant to pepsin hydrolysis, which usually results in complete loss of activity with unencapsulated IgY, suggesting that liposomal encapsulation is an effective means for protecting IgY under gastric conditions.

Animals↗