Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 253 records · Page 14Linked to original sources

PubMed1999

Assessment of lower extremity venous function using foot venous pressure measurement.

BACKGROUND: Measurement of foot venous pressure (FVP) is useful for evaluating chronic venous insufficiency (CVI) functionally, because CVI always causes venous hypertension. In the present study, the various FVP parameters were analysed according to the new classification of venous disorders based on clinical, aetiological, anatomical and pathophysiological data (the CEAP classification). METHODS: During the past 7 years, a total of 257 legs in 196 consecutive patients with CVI have been studied. The following FVP parameters were assessed: the percentage decrease in pressure from rest with manual calf compression, the rate of increase of pressure during 4 s after compression (4SR) and the time to 50 per cent recovery of pressure (RT50) after release of compression. RESULTS: The incidence of skin changes due to venous stasis increased as the percentage pressure drop and RT50 fell. In addition, a pressure drop of less than 72 per cent and an RT50 of less than 20 s could detect legs with skin changes with a sensitivity of 76 per cent and a specificity of 62 per cent. In legs with primary varicose veins, pressure drop, 4SR and RT50 values deteriorated in proportion to the severity of the associated deep venous reflux. CONCLUSION: FVP parameters correlate well with the severity of clinical manifestations and venous reflux, and could be used quantitatively to evaluate the severity of CVI.

Adolescent↗

PubMed1999

Parathyroid hormone gene polymorphisms in primary hyperparathyroidism.

OBJECTIVE: Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analysed the relationship between restriction fragment length polymorphisms of the PTH gene and the development of primary hyperparathyroidism (pHPT) as well as its severity. PATIENTS: Seventy-nine pHPT patients and 104 age-matched healthy controls were analysed. DESIGN AND MEASUREMENTS: PTH genotypes were determined by polymerase chain reaction and BstB I or Dra II restriction fragment length polymorphisms. The presence and absence of BstB I or Dra II restriction sites of the PTH gene were indicated by B and b or D and d, respectively. BMD levels at the lumbar spine and at the radius were measured in all subjects. Serum levels of calcium, phosphorus, alkaline phosphatase and intact PTH were measured in pHPT patients. RESULTS: There were no differences in the frequencies of these PTH genotypes between pHPT patients and controls. In control subjects, lumbar BMD was significantly higher in BB genotype than in Bb/bb genotypes. In pHPT patients, there was no difference of BMD between BB and Bb/bb genotypes. In pHPT patients, serum calcium level was significantly higher in those with the BB genotype than Bb/bb genotypes. On the other hand, there was no association between Dra II polymorphism and BMD in both controls and pHPT patients, but serum intact PTH level was significantly higher in DD genotype than Dd/dd genotype in pHPT patients. Moreover, serum levels of ALP and intact PTH were significantly higher in the PTH BBDD haplotype, compared to those in haplotypes other than BBDD. CONCLUSIONS: The present study suggests that the BstB I polymorphism of PTH gene is closely related to bone mineral density and that PTH gene polymorphisms do not seem to affect the development of primary hyperparathyroidism but may relate to the severity of primary hyperparathyroidism.

Alkaline Phosphatase↗

PubMed1999

Effect of recombinant human growth hormone in elderly osteoporotic women.

OBJECTIVE: Bone mineral density and growth hormone (GH) secretion rate both decline during normal human ageing. We evaluated the effects of recombinant human GH on markers of body composition and bone turnover in an open study in 8 elderly osteoporotic women aged 68-75 years (mean age 71 years). DESIGN: Subjects were treated with GH as a single daily subcutaneous injection (0.125 IU/kg/week for the first 4 weeks and subsequently 0.25 IU/kg/week) for 48 weeks. RESULTS: GH treatment caused a rapid (within 2 weeks) increase in serum levels of IGF-I and IGF-binding protein-3 (IGFBP-3) which was sustained throughout the study. Markers of bone formation and resorption were both gradually increased up to 24 weeks of GH treatment. The bone formation markers, osteocalcin (OC) and bone alkaline phosphatase, remained high during GH treatment, while the bone resorption marker, deoxypyridinoline (D-Pyr), tended to return to baseline levels after 24 weeks of GH therapy. GH treatment for 48 weeks caused a significant increase in hand grip and a decrease in waist/hip ratio. The mean percentage changes in bone mineral density (BMD) of mid-radius and lumbar spine were + 2.1% and + 1.2%, respectively, although they were not statistically significant. GH treatment was well tolerated and no major side-effects except mild oedema and joint pain were found. Since GH treatment produced durable increases in bone formation markers, BMD continued to be monitored after discontinuation of GH treatment for another 48 weeks, during which significant increases in radial and lumbar BMD (8.1 +/- 2.1 and 3.8 +/- 1.4% above pre- treatment values, respectively) were recorded. CONCLUSION: These results indicate that GH attenuates the decrease in muscle strength and bone mass as well as the gain of abdominal fat with ageing in elderly women. The present data provide useful information about the application of GH treatment in elderly women.

Aged↗

PubMed1999

Transcriptional regulation of fatty acid synthase gene by insulin/glucose, polyunsaturated fatty acid and leptin in hepatocytes and adipocytes in normal and genetically obese rats.

Transcriptional regulation of the fatty acid synthase (FAS) gene by insulin/glucose, polyunsaturated fatty acids and leptin was investigated in hepatocytes and adipocytes of Wistar fatty rats and their lean littermates. The sequence spanning nucleotides -57 to -35 of FAS gene, which is responsive to insulin/glucose stimulation [Fukuda, H., Iritani, N. & Noguchi, T. (1997) FEBS Lett. 406, 243-248], was linked to a reporter gene containing a heterologous promoter and transfected into rat hepatocytes or adipocytes. The activity of the reporter, chloramphenicol acetyltransferase, in the presence of glucose alone was similar in the primary cultured cells from the lean and obese rats. In the presence of insulin/glucose, however, chloramphenicol acetyltransferase activity was markedly increased in hepatocytes of lean rats, but was not significantly increased in those of obese rats. The stimulation by insulin/glucose was reduced in arachidonic acid-treated cells of lean rats. Similarly, the stimulation by insulin/glucose was reduced in leptin-treated cells and in cells from lean rats containing an expression vector encoding leptin. However, neither polyunsaturated fatty acids nor leptin-treated cells from obese rats responded to insulin-stimulation. The same effects were observed at endogenous FAS mRNA and enzyme levels. Similar results were seen in adipocytes, although the stimulation and suppression were much smaller than in hepatocytes. The insulin-binding capacities of the receptors of liver and adipose tissue were reduced in the presence of leptin or polyunsaturated fatty acids. Leptin and polyunsaturated fatty acids appeared to suppress the insulin stimulation of FAS transcription by reducing the insulin-binding capacities of receptors. Leptin converged on the insulin/glucose response element of FAS gene and suppressed the transcription.

Adipocytes↗

PubMed1999

Involvement of primary afferent C-fibres in touch-evoked pain (allodynia) induced by prostaglandin E2.

Nociceptive primary afferents have the capacity to induce a state of increased excitability in dorsal horn neurons of the spinal cord or central sensitization causing thermal hyperalgesia and touch-evoked pain (allodynia). It is believed that primary afferent C-fibres become hypersensitive and induce hyperalgesia and that low-threshold Abeta-fibres are responsible for induction of allodynia, the mechanisms of which remain elusive. We previously showed that intrathecal administration of prostaglandin E2 (PGE2) and prostaglandin F2alpha (PGF2alpha) induce allodynia in conscious mice. Here we demonstrated that selective elimination of C-fibres by neonatal capsaicin treatment resulted in the disappearance of allodynia induced by PGE2, but not that by PGF2alpha. PGE2-induced allodynia was not observed in N-methyl-D-aspartate (NMDA) receptor epsilon1 subunit knockout mice and was sensitive to morphine. In contrast, PGF2alpha-induced allodynia was not observed in NMDA epsilon4 subunit knockout mice and was insensitive to morphine. Furthermore, while PGF2alpha showed a capsaicin-insensitive feeble facilitatory action on evoked excitatory postsynaptic currents in dorsal horn neurons, PGE2 induced a long-lasting facilitation of evoked excitatory postsynaptic currents in a capsaicin-sensitive manner. Taken together, the present study demonstrates that there are two pathways for induction of allodynia and that capsaicin-sensitive C-fibres may participate in PGE2-induced allodynia.

Afferent Pathways↗

PubMed1999

Pharmacokinetics of NS-105, a novel cognition enhancer. 1st communication: absorption, metabolism and excretion in rats, dogs and monkeys after single administration of 14C-NS-105.

The absorption, metabolism and excretion of NS-105 ((+)-5-oxo-D-prolinepiperidinamide monohydrate, CAS 110958-19-5), a novel cognition enhancer, were studied in rats, dogs and monkeys after intravenous or oral administration of 14C-NS-105. The protein binding of this drug was also investigated in vivo and in vitro. After the intravenous and oral administrations of 14C-NS-105, the unchanged drug accounted for most of the plasma radioactivity in all the species tested. After the intravenous injection, the plasma concentration of NS-105 decreased monoexponentially with respective elimination half-lives of 0.67, 2.1 and 1.3 h for the rats, dogs and monkeys. After the oral administration, the plasma concentration of NS-105 reached a maximum within 1 h, then decreased as in intravenous administration in all the species tested. NS-105 was almost completely absorbed from the small intestine, and first-pass metabolism was very limited. As a result, its systemic availability was high; 97% in the rats, 90% in the dogs and 79% in the monkeys. No significant sex-related differences in the plasma concentration profiles of radioactivity were observed in the rats after the oral administration of 14C-NS-105 (p > 0.05). Food affected the absorption of NS-105. The Cmax and AUC0-infinity of radioactivity concentration were proportional to the dose for 1-100 mg/kg of 14C-NS-105. There were no marked differences between the intravenous and oral routes in the compositions of urinary radioactivity for any of the species tested. In the urine of dogs, LAM-162 (oxidative metabolite with C-N cleavage of the piperidine ring), LAM-79 (metabolite with 4-hydroxylated piperidine ring), LAM-163 (metabolite with 3-hydroxylated piperidine ring) and M1 (not identified) accounted for 20%, 3%, 6% and 1% of the urinary radioactivity, respectively. In the urine of rats and monkeys, LAM-162 and LAM-79 accounted for 1-6% of the urinary radioactivity, but LAM-163 and M1 were not detected. After the intravenous and oral administrations, NS-105 was primarily eliminated by renal excretion in all the species tested, approximately 90% of the dose being excreted unchanged in the urine for rats and monkeys and 60% of it for dogs. Excretions of radioactivity in the bile and exhaled air in rats were less than 1.4% of the dose, and lymphatic absorption of radioactivity was only 0.3% of the dose. The percentage of 14C-NS-105 bound to serum proteins was less than 3.3% in all the animal species tested, including humans.

Administration, Oral↗

PubMed1999

Metabolic fate of a new histamine H2-receptor antagonist, Z-300, in rat.

1. The metabolisms of (N-[3-[3-(piperidinomethyl)-phenoxy]-propyl]-2-(2-hydroxyethyl-1-t hio) acetamide.2-(4-hydroxy benzoyl) benzoate) (Z-300) in rat have been studied. 2. Five metabolites were identified, namely as sulphoxide (SO), sulphone (SO2), phenol (PH), propionic acid (PA) and thioglycolic acid (TH) derivatives. Furthermore, two metabolites, M1 and M2, were proposed as PH conjugated to sulphate and glucuronic acid respectively. 3. There were several metabolites in the plasma samples after oral administration of 14C-Z-300. The main metabolites were PH (mainly existing as the conjugates), PA and SO, and Z-300 was present as <10% of plasma radioactivity. SO2 and TH were barely detected in plasma. In the urine, the composition of metabolites was similar to that in the plasma. In the bile, the main metabolites were PH (mainly existing as the conjugates) and SO, and very little Z-300 was detected. In the faeces, the main compounds were Z-300 and TH, and very little SO. 4. During in vitro metabolism experiments, Z-300 was metabolized mainly in the liver, and a little in the kidney and lung. PH or its conjugates were produced little on the in vitro metabolism; this was different from that found in the in vivo experiment. The metabolism of Z-300 to SO appeared to be catalysed by cytochrome P450 rather than the flavin-containing monooxygenase. Both hepatic clearance calculated from the in vitro metabolism experiment (28.9 ml/min/kg) and from the liver perfusion metabolism experiment (33.2 ml/min/kg) were lower than the total clearance from the in vivo experiment (119 ml/min/kg). 5. After administration of 14C-SO into the caecum of rat, SO was converted to Z-300 and excreted in the faeces. 14C-SO was reduced by incubation for 4 h within the caecal content of rat under an anaerobic condition in vitro. The results suggest that SO was reduced to Z-300 by gut flora in the lower intestine.

Acetamides↗

PubMed1999

Pharmacokinetics of a new histamine H2-receptor antagonist, Z-300, in rat and dog.

1. The plasma level of Z-300 reached a maximum (Cmax) at 30 min after the oral administration of Z-300 to dog, and disappeared from the systemic circulation with a half-life of 8-9 h. The bioavailability of Z-300 was 52% after the oral administration of Z-300, 3 mg/kg. At doses ranging from 3 to 30 mg/kg, Cmax and AUC (area under the plasma concentration-time curve) were proportional to the dose. 2. The plasma level of Z-300 reached Cmax at 10 min after the oral administration of Z-300 to rat, and disappeared from the systemic circulation with a half-life of 0.8-1.6 h. The bioavailability of Z-300 was 39% after the oral administration of Z-300, 10 mg/kg, and there was a non-linear relationship between the plasma level-time profile of Z-300 and the administered dose (3-50 mg/kg). 3. The binding of Z-300 to plasma protein was 92% in man, 65% in dog and 25% in rat. It is suggested that these species differences were due to the content of alpha1-acid glycoprotein (alpha1-AG), because Z-300 bound more strongly to alpha1-AG than to albumin.

Acetamides↗

PubMed1999

Oral triacylglycerols regulate plasma glucagon-like peptide-1(7-36) and insulin levels in normal and especially in obese rats.

In a previous study of glucose tolerance, plasma insulin levels were greatly elevated in genetically obese Wistar fatty rats but not lean rats fed a diet containing polyunsaturated fatty acids. In the present study, triacylglycerol-regulation of levels of circulating insulin and glucagon-like peptide-1 (7-36) (GLP-1) has been investigated in these rats. In the glucose tolerance test, the two plasma insulin peaks appeared in obese and lean rats intubated with glucose + corn oil, at 15- 30 min and 4 h, whereas only the first peak appeared in rats intubated with glucose alone, although the glucose response did not differ. After intubation of corn oil only, the insulin peak at 15 min was not detected but the peak at 4h was large. The two plasma GLP-1 peaks appeared 15 min and 4 h after intubation of glucose + corn oil similarly to the insulin responses, although the first peak was small and the second peak was very large. A small peak at 15 min was not significant in rats intubated glucose alone and no peak was seen at 4 h. The GLP-1 concentrations were significantly higher in the following order: portal vein > inferior vena cava > tail vein. The plasma GLP-1 increment in response to oral triacylglycerols was significantly higher in obese rats than in lean rats as was the insulin increment. Thus, oral triacylglycerols (possibly polyunsaturated) appeared to act at the gut lumen to stimulate GLP-1 secretion, which may be responsible for the second (4 h) insulin peak.

Administration, Oral↗

PubMed1999

Facile degradation of apolipoprotein B by radical reactions and the presence of cleaved proteins in serum.

A facile cleavage of peptide bonds of apolipoprotein B (apoB) by radical reaction is reported. When human LDL was subjected to oxidative damage using Cu2+, extensive degradation of apoB was observed based on immunoblotting. The degradation of apoB was inhibited by radical scavengers (beta-mercaptoethanol, butylated hydroxytoluene, and probucol) and promoted by a radical initiator [2, 2'-azobis(2-amidinopropane)dihydrochloride]. When human serum was treated with Cu2+, a similar cleavage pattern of apoB was observed. The cleaved apoB proteins were also detected in normal serum on the basis of immunoblots. These results suggest that apoB is highly reactive toward radicals in vitro and in vivo, with reaction resulting in the cleavage of peptide bonds.

Adult↗

PubMed1999

Preischemic and postischemic treatment with a new Na+/H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion.

This study describes the pharmacologic profile of a new Na+/H(+)-exchange inhibitor, FR183998, in anesthetized rats. FR183998 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes with median inhibitory (IC50) value of 0.3 nM. Treatment with FR183998 (0.01-0.32 mg/kg, i.v.) reduced or completely abolished ventricular fibrillation and mortality induced by 5-min ischemia followed by reperfusion, when it was administered not only 5 min before ischemia but also 1 min before reperfusion. Myocardial infarct size induced by 30-min ischemia and 60-min reperfusion was reduced significantly in a dose-dependent manner by FR183998 (0.1-1.0 mg/kg, i.v.) when the drug was administered preischemically or at an early phase of ischemia. The ventricular tachycardia and the ventricular fibrillation observed during the ischemic period also were suppressed significantly. These results indicate that FR183998 has a strong inhibitory effect on Na+/H+ exchange and suggest that treatment with FR183998 either before or immediately after the onset of ischemia can prevent the occurrence of arrhythmias and myocardial cell necrosis in situations of ischemia and reperfusion.

Anesthesia↗

PubMed1999

Outcome of epilepsy surgery in the first three years of life.

PURPOSE: We analyzed our experience over a 6-year period with early-childhood patients who had undergone epilepsy surgery, and investigated the surgical outcomes. METHOD: We reviewed the medical records of 23 children, ages 0-3 years, who underwent epilepsy surgery between 1991 and 1996. RESULTS: Twenty children had partial seizures; two had infantile spasms; and one had generalized tonic-clonic seizures at onset. The mean age at onset of seizures was 4.7 months, and the mean age at time of surgery was 15.3 months. A total of 32 operations (21 focal cortical resections and 11 hemispherectomies) was performed. Five of 12 children with seizures secondary to a neuronal migration disorder had reoperations, including three who ultimately underwent complete hemispherectomy. The pathology consisted of hemimegalencephaly in three patients, focal cortical dysplasia (FCD) in eight, tuberous sclerosis in one, Sturge-Weber syndrome (SWS) in five, infarction in two, low-grade glioma (LGG) in three, and post-herpes simplex virus encephalitis (HSE) in one. The follow-up period ranged from 1 to 6.5 years (mean, 3.2 years) from patients' last operation. The seizure outcome according to Engel's criteria was class I in 12 patients, class II in three, class III in six and class IV in two. CONCLUSIONS: Seizure outcomes after surgery were less favorable in infants with FCD than in those with SWS and LGG. Seizure outcome for the patients with hemispherectomies was excellent, compared with those who had focal cortical resections.

Age Factors↗

PubMed1999

Massive gastrointestinal hemorrhage in systemic lupus erythematosus: successful treatment with corticosteroid pulse therapy.

Although mesenteric vasculitis due to systemic lupus erythematosus (SLE) is relatively uncommon, it is the most dangerous manifestation associated with high mortality. We describe the case of a SLE patient with life-threatening gastrointestinal hemorrhage due to mesenteric vasculitis in whom methylprednisolone pulse therapy was quite effective in controlling the hemorrhage and resulted in a satisfactory long term outcome. A 47-yr-old woman presenting with high fever, rash, and melena was diagnosed with SLE from positive antinuclear antibodies, anti-dsDNA, and low complement titers. Although fever and rash subsided with administration of prednisolone, massive hematemesis appeared with melena. Endoscopy demonstrated bleeding ulceration of the antrum, which was intractable despite intensive antiulcer therapy and transfusion. Surgical exploration revealed ileal penetration, and multiple bleeding ulcerations were observed over the resected ileum as well as the antral ulceration. However, bleeding persisted after surgery and surgical findings prompted us to select methylprednisolone pulse. Hemorrhage responded promptly to the therapy, and the patient has remained well since then for >10 yr. Our report indicates that corticosteroid pulse may serve as one of the therapeutic options for SLE with massive hemorrhage due to widespread mesenteric vasculitis.

Anti-Inflammatory Agents↗

PubMed1999

(123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson's disease.

OBJECTIVES: (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is clinically used to estimate local myocardial sympathetic nerve damage in some forms of heart disease, autonomic nerve disturbance in diabetic neuropathy, and disturbance of the autonomic nervous system in neurodegenerative disease. In the present study, examinations were performed to clarify (1) the proportion of cardiac sympathetic nerve disturbance in Parkinson's disease, (2) the usefulness of (123)I-MIBG myocardial scintigraphy to detect sympathetic nerve disturbances compared with autonomic function tests, (3) cardiac function in patients who have a decreased MIBG uptake in (123)I-MIBG myocardial scintigraphy, (4) the usefulness of (123)I-MIBG myocardial scintigraphy to differentiate Parkinson's disease from the other neurological diseases mimicking it. METHODS: (123)I-MIBG myocardial scintigraphy was performed, together with autonomic function tests and cardiac examinations in 46 patients with Parkinson's disease and 25 patients with vascular parkinsonism, essential tremor, or multiple system atrophy. RESULTS: In an anterior image study, the average count per pixel in heart to mediastinum (H/M) ratio decreased in 80% of the patients with Parkinson's disease in the early phase and 84% in the late phase. The mean H/M ratio in Parkinson's disease was significantly lower than that in controls and the other diseases. The H/M ratio tended to decrease with the disease progression. In almost half of the patients in Hoehn and Yahr stage I, the H/M ratio was already decreased. The sympathetic skin response in upper and lower limbs, head up tilt test, and coefficient of variation of R-R interval were abnormal in 17%, 31%, 30%, and 17% of the patients, respectively. All the patients with abnormal autonomic functions were in Hoehn and Yahr stage III, IV, or V. Echocardiography showed normal left ventricular function. Twenty four hour Holter electrocardiography detected no serious arrhythmias except for one patient with non-sustained ventricular tachycardia. CONCLUSION: (123)I-MIBG myocardial scintigraphy might detect early disturbances of the sympathetic nervous system in Parkinson's disease and might give useful diagnostic information to differentiate vascular parkinsonism, essential tremor, and multiple system atrophy from Parkinson's disease.

3-Iodobenzylguanidine↗

PubMed1999

Monomorphic agranular natural killer cell lymphoma/leukemia with no Epstein-Barr virus association.

The conceptual view of natural killer (NK) cell malignancies has recently undergone a significant evolution. The majority of such diseases are associated with Epstein-Barr virus (EBV), while only a limited number of EBV-negative cases has been reported. We report an unusual case of NK cell lymphoma/leukemia showing a monomorphic histology, absence of intracytoplasmic azurophilic granules, and no EBV association. The patient was a 57-year-old woman who died 26 months after the diagnosis. Autopsy revealed tumor infiltration in the liver, spleen, lymph node, blood, and bone marrow. There was no involvement of the skin or nasal cavity throughout the clinical course. The tumor showed the monotonous proliferation of medium-sized cells without intracytoplasmic azurophilic granules. Phenotypic analysis showed CD2+, CD3/Leu4-, cytoplasmic CD3epsilon+, CD4-, CD5-, CD7+, CD8-, CD16-, CD38+, CD56+, CD57-, TdT-, granzyme B-, and TIA1+ phenotype. There were no detectable rearrangements of T cell receptor genes or immunoglobulin heavy chain genes. Furthermore, there were no EBV-encoded small RNAs. These findings provide information to improve the understanding of poorly defined entities, i.e. aggressive NK cell lymphoma/leukemia and blastic NK cell lymphoma/leukemia.

Colonic Neoplasms↗

PubMed1999

Role of nitric oxide-cGMP pathway in adrenomedullin-induced vasodilation in the rat.

We previously reported that adrenomedullin (AM), a potent vasodilator peptide discovered in pheochromocytoma cells, stimulates nitric oxide (NO) release in the rat kidney. To further investigate whether the NO-cGMP pathway is involved in the mechanisms of AM-induced vasodilation, we examined the effects of E-4021, a cGMP-specific phosphodiesterase inhibitor, on AM-induced vasorelaxation in aortic rings and perfused kidneys isolated from Wistar rats. We also measured NO release from the kidneys using a chemiluminescence assay. AM (10(-10) to 10(-7) mol/L) relaxed the aorta precontracted with phenylephrine in a dose-dependent manner. Denudation of endothelium (E) attenuated the vasodilatory action of AM (10(-7) mol/L AM: intact (E+) -25.7+/-5.2% versus denuded (E-) -7. 8+/-0.6%, P<0.05). On the other hand, pretreatment with 10(-8) mol/L E-4021 augmented AM-induced vasorelaxation in the intact aorta (-49. 0+/-7.9%, P<0.05) but not in the denuded one. E-4021 also enhanced acetylcholine (ACh)-induced vasorelaxation in the rat intact aorta (10(-7) mol/L ACh -36.6+/-8.4% versus 10(-8) mol/L E-4021+10(-7) mol/L ACh -62.7+/-3.1%, P<0.05). In perfused kidneys, AM-induced vasorelaxation was also augmented by preincubation with E-4021 (10(-9) mol/L AM -15.4+/-0.6% versus 10(-8) mol/L E-4021+10(-9) mol/L AM -23.6+/-1.2%, P<0.01). AM significantly increased NO release from rat kidneys (DeltaNO: +11.3+/-0.8 fmol. min-1. g-1 kidney at 10(-9) mol/L AM), which was not affected by E-4021. E-4021 enhanced ACh-induced vasorelaxation (10(-9) mol/L ACh -9.7+/-1.7% versus 10(-8) mol/L E-4021+10(-9) mol/L ACh -18.8+/-2.9%, P<0.01) but did not affect ACh-induced NO release from the kidneys. In the aorta and the kidney, 10(-4) mol/L of NG-nitro-L-arginine methyl ester, an NO synthase inhibitor, and 10(-5) mol/L of methylene blue, a guanylate cyclase inhibitor, reduced the vasodilatory effect of AM. These results suggest that the NO-cGMP pathway is involved in the mechanism of AM-induced vasorelaxation, at least in the rat aorta and kidney.

Adrenomedullin↗

PubMed1999

Progressive sensorineural hearing impairment in professional fishery divers.

There have been many reports of a high rate of hearing impairment in divers. A prospective study was performed to determine whether sensorineural hearing acuity in the same divers deteriorated faster than in a normal population as they continued diving. After an observation period of approximately 5 years, audiometric examination was performed on a group of professional fishery divers who had normal hearing or sensorineural hearing loss at the time of initial study. Thirty-three ears of 18 divers were included in statistical analyses. The average hearing deterioration in the divers in 5 years, after elimination of the aging effect, was 6.6 dB (SD 4.5) and was statistically significant. We concluded that the hearing acuity of our subjects deteriorated faster than that of normal Japanese.

Adult↗

PubMed1999

Profiles of aprindine, cibenzoline, pilsicainide and pirmenol in the framework of the Sicilian Gambit. The Guideline Committee for Clinical Use of Antiarrhythmic Drugs in Japan (Working Group of Arrhythmias of the Japanese Society of Electrocardiology).

The Vaughan Williams classification has been used widely by clinicians, cardiologists and researchers engaged in antiarrhythmic drug development and testing in many countries throughout the world since its initial proposal in the early 1970s. However, a major criticism of the Vaughan Williams system arose from the extent to which the categorization of drugs into classes I-IV led to oversimplified views of both shared and divergent actions. The Sicilian Gambit proposed a two-dimensional tabular framework for display of drug actions to solve these problems. From April to December 1996, members of the Guideline Committee met to discuss pharmacologic profiles of 4 antiarrhythmic drugs (aprindine, cibenzoline, pilsicainide, and pirmenol) that were not included in the original spreadsheet but are used widely in clinical practice in Japan. The discussion aimed to fit the drug profiles into the Gambit framework based on all the important literature published to date regarding the actions of the 4 drugs. This report is a summary of that deliberation.

Animals↗