[The combined effects of three analgesics in analgesic activity and acute toxicity].
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Analgesics↗
Biomedical subjects
K Shigenobu
Publications and source records attributed to K Shigenobu.
Membrane effects of pronethalol on the mammalian heart muscle fiber.
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Animals↗
Mid-term clinical results of Graf stabilization for lumbar degenerative pathologies. a minimum 2-year follow-up.
BACKGROUND CONTEXT: Spinal fusion has some adverse effects, such as nonunion and pain at the site of grafted bone, and fusion with rigid spinal instrumentation especially may have the possibility of increasing mechanical stress on the segments adjacent to the site of fusion. The theory of the Graf system is that it will decrease adjacent disc deterioration because of maintenance of regional lordosis with flexibility and restriction of the motion of unstable segments without rigid spinal fusion. PURPOSE: To assess the clinical and radiologic results of Graf stabilization for lumbar degenerative disorders with minimal or mild instability. STUDY DESIGN: This is a retrospective study examining the mid-term results of Graf stabilization. PATIENT SAMPLE: In total, 59 patients underwent Graf ligamentoplasty and adequate decompression from April 1993 to September 1997. The subjects were 30 men and 29 women, and the mean age at the time of surgery was 60.6 years, ranging from 23 to 82 years. The average follow-up period was 3 years and 5 months, ranging from 2 years to 5 years and 10 months. OUTCOME MEASURES: We evaluated the surgical results using a scoring system, a visual analog scale, and radiological measurements. METHODS: The results were assessed according to a clinical scoring system established by the Japanese Orthopaedic Association (JOA score) and ratings based on a visual analog scale. Through analysis of x-ray images, the sagittal alignment (regional lordosis) and the range of motion (ROM) of the stabilized segments were measured in all cases, and the percentage of segments slipping and posterior disc height were determined for 29 patients with degenerative spondylolisthesis. RESULTS: Clinical scores and low back pain ratings based on a visual analog scale were significantly improved at the time of final follow-up compared with the preoperative values. Regional alignment of the operative segments was maintained in lordosis at the time of final follow-up. Preoperative ROM was significantly reduced at the time of final follow-up. There were no statistical differences in percentage of slippage or percentage of posterior disc height between the final follow-up values and the preoperative values. CONCLUSIONS: Our clinical results indicate that the Graf system is a suitable treatment option for mild and early lumbar degenerative diseases with minimum flexion instability of less than 10 degrees.
Adult↗
Enhancement of methoxamine-induced contractile responses of rat ventricular muscle in streptozotocin-induced diabetes is associated with alpha1A adrenoceptor upregulation.
AIM: To clarify the time-related changes in cardiac function and the mechanism underlying the cardiac dysfunction present in diabetes mellitus, we studied mechanical responses induced by alpha(1)- and beta-adrenoceptors, the Ca(2+)-entry promoter Bay K 8644- and ryanodine (an agent known to inhibit Ca(2+) release from the sarcoplasmic reticulum) in papillary muscles from streptozotocin (STZ)-induced diabetic and age-matched control rats. METHODS: Male Wistar rats received a single injection of STZ (60 mg kg(-1)) via the tail vein to induce diabetes. For the mechanical studies, papillary muscle preparations were suspended in an organ bath and isometric contractions were measured in 1-, 4-, and 10-week STZ-induced diabetic and age-matched control rats. RESULTS: In 1-week diabetic rats, the contractions induced by isoproterenol, methoxamine and Bay K 8644 were unchanged (vs. age-matched controls). In 4-week diabetic rats, (a) the isoproterenol- and Bay K 8644-induced contractions were impaired, (b) sensitivity to ryanodine was reduced, whereas (c) the methoxamine-induced contraction was unchanged. In 10-week diabetic rats, the isoproterenol- and Bay K 8644-induced contractile responses were impaired and the sensitivity to ryanodine was reduced, but in sharp contrast the methoxamine-induced contraction was enhanced. Both the mRNA level for the alpha(1A) adrenoceptor (but not the alpha(1B) or alpha(1D) mRNAs) and alpha(1A) adrenoceptor protein were increased in 10-week diabetic rats (vs. age-matched controls). CONCLUSION: These results suggest that impairments of beta-adrenergic and Ca(2+)-handling mechanisms occur early in the development of cardiomyopathy in STZ-induced diabetic rats, and that this is followed by augmentation of alpha(1A) adrenoceptor-mediated inotropy due to alpha(1A) adrenoceptor upregulation.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Utility of (99m)Tc-HM-PAO SPECT hippocampal image to diagnose early stages of Alzheimer's disease using semiquantitative analysis.
OBJECTIVE: Examination of the utility of (99m)Tc-hexamethylpropylene amine oxide ((99m)Tc-HM-PAO) SPECT hippocampal image to diagnose early stages of Alzheimer's disease (AD) using semiquantitative analysis. SUBJECTS: 10 early-stage AD patients and 8 normal sex-matched elderly controls. SETTING: Outpatient division of the Ehime University Hospital. METHOD: We performed (99m)Tc-HM-PAO SPECT perfusion imaging in each subject. A semiquantitative method of assessing regional variation was used. The regions of interest for temporal regions were set at images parallel to the long axis of the hippocampal formation which were reconstructed at 30 degrees negative to the orbitomeatal line and those for other regions were set on ordinary transaxial images. RESULTS: The regional cerebral blood flow ratio of the bilateral medial temporal lobe at the hippocampal image was significantly lower in the AD subjects than in the normally aged controls without any other differences in ordinary transaxial images. CONCLUSION: This study suggests that (99m)Tc-HM-PAO SPECT hippocampal images might be a helpful tool for the diagnosis of very-early-stage AD.
Aged↗
Relationship between blood flow kinetics and severity of Alzheimer's disease: assessment of severity using a questionnaire-type examination, Alzheimer's disease assessment scale, cognitive sub-scale (ADAS(cog)).
We assessed hemokinetics associated with changes in Alzheimer's disease (AD) severity in 90 AD patients by researching the relationship between AD Assessment Scale, cognitive sub-scale (ADAS(cog)) scores and regional cerebral blood flow (rCBF). In the present study, we employed the questionnaire-type ADAS(cog) examination to accurately assess the severity of AD. Between five groups classified on the basis of ADAS(cog) score, significant differences were observed in parietal, lateral temporal and superior frontal rCBF. In addition, in parietal and lateral temporal regions, significant correlations were also observed between ADAS(cog) score and rCBF. In superior frontal rCBF, significant differences were noted only between group 5 (> or =40 ADAS(cog) points) and each of the other groups; there was no significant correlation between rCBF and ADAS(cog) score. Thus, we propose the following mechanism for blood flow kinetics associated with changed severity: In an early stage of AD, blood flow in the medial temporal cortex is impaired, and gradually involves the temporoparietal regions. While the medial temporal impairment of blood flow reaches a plateau, temporoparietal blood flow continues to be impaired well into a severe stage, at which point blood flow impairment in the frontal region is initiated.
Aged↗
Frontotemporal lobar degeneration: a study in Japan.
Frontotemporal lobar degeneration is the most common form of cortical dementia occurring in the presenium after Alzheimer's disease. We analyzed two types of frontotemporal dementia (FTD) and semantic dementia (SD) selected from a consecutive series of outpatients based on neuropsychological symptoms, psychiatric symptoms and abnormal behavior. In our series of 134 patients with primary degenerative dementia, there were 16 cases of FTD and 6 cases of SD. Patients with subgroups of FTD and patients with SD were distinguishable only by the presence of aphasia in the latter group. They were not distinguishable from one another by other neuropsychological examinations, behavioral abnormalities or psychiatric symptoms assessed with the Neuropsychiatric Inventory.
Aged↗
Vasorelaxing and receptor binding properties of NZ-105, a novel dihydropyridine derivative, in isolated rabbit aorta.
The vasorelaxing and dihydropyridine receptor binding properties of NZ-105, a new dihydropyridine derivative, were studied using isolated rabbit aorta, and compared with those of nicardipine, nifedipine and diltiazem. NZ-105 (3 x 10(-10)-3 x 10(-9) M), nicardipine (3 x 10(-10), 10(-9) M), and diltiazem (3 x 10(-7), 10(-6) M) selectively relaxed aortic strips precontracted with high-K+ solution (50 mM) with little effect on strips precontracted with phenylephrine (10(-5) M) or clonidine (10(-6) M). The relaxation produced by NZ-105 was of very slow onset, and no recovery was observed after a 2 hr washout with high-K+ or normal bathing solution. NZ-105 (3 x 10(-10)-3 x 10(-9) M) caused a non-parallel depression of the concentration-response curve for the CaCl2-induced contraction in high-K(+)-depolarized rabbit aorta, whereas nicardipine (10(-10), 3 x 10(-10) M), nifedipine (10(-9), 3 x 10(-9) M) and diltiazem (10(-7), 3 x 10(-7) M) all produced a concentration-related rightward displacement of the curve. The depression induced by NZ-105, but not by nicardipine, became greater as the period of preincubation with the drug was prolonged. NZ-105, nicardipine and diltiazem, at the very high concentration of 10(-6) M, caused a slight and noncompetitive inhibition of the concentration-response curves for norepinephrine, prostaglandin F2 alpha, angiotensin II and 5-hydroxytryptamine. NZ-105 displaced 3H-nitrendipine binding to rabbit aortic membranes in a manner similar to that of nicardipine and nifedipine, and this was also incubation time-dependent. These results indicate that NZ-105 possesses selective calcium antagonist properties, with respect to the rabbit isolated vascular smooth muscle, which are of very slow onset and long-lasting. The slow onset of the vasorelaxation may be due to a slow association rate to dihydropyridine receptors. These pharmacological properties of NZ-105 may, at least in part, be responsible for the slow onset and long duration of its antihypertensive action in vivo.
Angiotensin II↗
Cardiac and vascular effects of NZ-105, a novel dihydropyridine derivative, in vitro.
The cardiovascular selectivity of NZ-105, a novel dihydropyridine derivative, was studied in vitro in comparison with nicardipine and other calcium antagonists. NZ-105 and nicardipine (10(-9), 10(-8) M) decreased the spontaneous contraction rate of the isolated guinea-pig right atrium. On the other hand, NZ-105, even at concentrations as high as 10(-6) M, slightly diminished the contractile force of the electrically driven left atrium, while nicardipine strongly and dose-dependently decreased the contractile force at a concentration of 10(-7) M by 39.9% and at 10(-6) M by 72.1%. NZ-105, nicardipine and diltiazem, at concentrations below 10(-6) M, caused no or only a slight depression of isoproterenol-induced increases in the contractile force of the driven left atrium. In left atrium partially depolarized with high K+ (22 mM) in the presence of 10(-6) M of isoproterenol, NZ-105 (10(-8)-10(-6) M), nicardipine (10(-9)-10(-7) M) and diltiazem (10(-7), 10(-6) M) produced both a concentration-related displacement of the concentration-response curves for CaCl2 to the right and a depression of the maximum response to CaCl2. In various rabbit blood vessels depolarized with high K+ (100 mM) (coronary, superior mesenteric, renal and femoral arteries and saphenous vein). NZ-105 (3 x 10(-10)-10(-8) M) caused a non-parallel depression of the concentration-response curves for CaCl2-induced contractions. The calcium-antagonizing effect of NZ-105 was strongest in the basilar artery. NZ-105 displaced the [3H]-nitrendipine binding to rabbit cardiac and aortic membranes in a manner similar to nicardipine and nifedipine. The Ki values of these compounds, with respect to cardiac membranes, were several times larger than in the case of aortic membranes. The Ki value of NZ-105, but not of nicardipine, grew smaller as the preincubation period with the drug increased. These findings indicate that NZ-105 possesses selective calcium-antagonizing properties in vascular smooth muscle, especially in the basilar artery, when compared with cardiac muscle. The negative chronotropic action of NZ-105 was more potent than its inotropic action. On the basis of these pharmacological properties, NZ-105 is considered to be a useful drug for the treatment of cardiovascular disorders.
Animals↗
Antihypertensive and diuretic effects of NZ-105, a novel dihydropyridine derivative.
Studies on the antihypertensive and diuretic actions of NZ-105, a new dihydropyridine derivative, were performed in comparison with nicardipine. NZ-105 and nicardipine (5, 10 and 20 mg/kg, p.o.) dose-dependently decreased systolic blood pressure in three types of experimentally hypertensive rats, including spontaneously hypertensive rats, renal hypertensive rats and deoxycorticosterone acetate-salt hypertensive rats and normotensive Wistar-strain rats. The hypotensive effects were larger in hypertensive rats than in normotensive Wistar rats. The hypotensive actions of NZ-105 were very slow in onset and long-lasting in all models, e.g., the hypotension by NZ-105 (10 mg/kg, p.o.) reached a peak (-52 mmHg) at 3 hr and lasted for more than 9 hr in spontaneously hypertensive rats. The hypotensive action in spontaneously hypertensive rats was reproducible after repeated dosing twice a day for 29 days. The hypotensive action after i.v. injection of NZ-105 (0.1 mg/kg) in spontaneously hypertensive rats was also slow in onset (peak time: 10 min) and long-lasting (more than 120 min). The hypotensive potency of NZ-105 was about the same as that of nicardipine, but the increment in heart rate was smaller than in the case of nicardipine. Both NZ-105 and nicardipine showed diuretic and natriuretic actions in spontaneously hypertensive rats. After repeated administration, these actions of NZ-105 were unchanged, whereas those of nicardipine were reduced. These results suggest that NZ-105 is a useful antihypertensive drug with concomitant diuretic effects.
Animals↗
Effect of beraprost sodium on changes in action potentials during hypoxia as compared with propranolol, diltiazem and glibenclamide in guinea-pig ventricular muscle.
The inhibitory effect of beraprost on the transmembrane action potentials was compared with other cardioprotective drugs during hypoxia in guinea-pig isolated right ventricular muscle. Glibenclamide, like beraprost, inhibited the decrease of the action potential duration, but propanolol and diltiazem did not affect this decrease during hypoxia. In beraprost-treated preparations, the decrease of the myocardial K+ content during hypoxia was inhibited. Furthermore, beraprost prevented the action potential shortening during metabolic inhibition by 2,4-dinitrophenol. It is suggested that beraprost may inhibit the hypoxia- and 2,4-dinitrophenol-induced shortening of the action potential duration by preserving the muscular ATP level. Accordingly, beraprost may have beneficial effects both during hypoxia and metabolic inhibition.
2,4-Dinitrophenol↗