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S Suda

Publications and source records attributed to S Suda.

At least 55 records · Page 3Linked to original sources
PubMed1992

Imidazo[1,2-alpha]pyridines. III. Synthesis and bradycardic activity of new 5-imidazo[1,2-alpha]pyridin-6-ylpyridine derivatives.

Structural modification of the cardiotonic agent, loprinone (E-1020, 1), suggested by data that it has a less positive chronotropic effect than milrinone (15), led us to find novel bradycardic agents that were structurally different from homoveratryl amine derivatives. Alkyl-oxy, -thio, and -amino derivatives at the 2-position of the pyridine ring of 1 produced bradycardic activity without a significant effect on blood pressure and myocardial contractility. Aryloxy analogues also decreased heart rate, and members with an electron-withdrawing group at the ortho position of the phenyl ring showed higher activity. Replacement of the imidazo[1,2-alpha]pyridine with pyridine resulted in diminished activity. The mechanism of bradycardic activity of these compounds seems to be direct action on the sinus node.

Animals↗
PubMed1992

[Effects of tiropramide on the activity of lower urinary tract in dogs and its interpretation].

The rhythmic contractions of urinary bladder under constant volume condition were evoked in decerebrate and de-anesthetized dogs, while various myogenic and nerve-mediated electrical and mechanical activities of smooth muscles were recorded from in vivo pelvic viscera. The vesical rhythmic contractions were transiently and partially blocked by intravenous application of tiropromide. This 'partial' block showed a good contrast to the 'complete' block of identical contractions, which was observed after application of oxybutynin, known as a potent anti-muscarinic drug. The bladder voiding cycles were observed in other decerebrate dogs, while the warmed Ringer solution was infused at a steady rate into the dome of the bladder until principal voiding contraction occurred in cystometric recordings. The initiation of voiding contraction was markedly delayed after intravenous injection of tiropramide. The delay of principal contraction was found to be due to successive appearance of falling waves in cystometric recordings. As a evident contrast, terodiline caused a significant reduction of voiding contraction height and shortening of clonic discharge phase of external urethral sphincters during voiding cycle. It is concluded that tiropramide does not reveal anti-muscarinic action which oxybutynin or terodiline does really show, instead tiropramide acts principally on bladder detrusor itself, especially on its relaxation phase of premature contraction to be prolonged. The evidences were also presented for electrophysiological identification of bladder detrusor and urethral smooth muscle.

Action Potentials↗
PubMed1992

[Electrical activities of urethral circular muscle and bladder detrusor and their control, examined by in vivo dogs].

While the micturition reflex was induced in dog by infusion of Ringer solution into the bladder, the following four types of electrical activity were picked up by two bipolar wire electrodes, embedded in the posterior wall of bladder and in the prostatic part of male urethra; 'intravesical ureter potential' and 'detrusor spike' by bladder electrode, and 'slow wave' and 'external sphincter spike' by urethral electrode. The relative size, respective rhythm and timing of discharge during voiding cycle were specific for each of them and they were readily identifiable for their own sources. The 'ureter potential' was not actively related to the voiding cycle but its triphasic wave form was dissociated at the maximum contraction phase of the bladder. Unexpected finding was the 'quasi-synchronization' of discharges between detrusor and external sphincter. The entire discharges in both muscles were consisted of 'initial burst', 'intermittent inhibition' and 'prolonged after-discharge'. The initial burst of detrusor was definitely delayed in comparison with that of external sphincter, but the end of prolonged after-discharges was again synchronized in both muscles. The possible mechanism for synchronization was discussed. The 'slow wave' was sometimes superposed on the tonic discharge of external sphincter recorded by same wire-electrode in urethral wall, therefore, their properties were analyzed under the condition of 'immobilization' of external sphincter. The sustained waxing and waning 'slow waves', observed in all female urethrae and one-fifth of male urethrae, were markedly suppressed by elicitation of isovolumetric rhythmic contractions of bladder with fall of intraurethral pressure. This bladder-dependent behavior of 'slow wave' was interpreted as a sign of 'urinary' sphincteric activity of urethral circular muscle. On the other hand, 'spontaneous' cyclic activation of 'slow wave' which was seen in about four-fifths of male urethrae and was not dependent upon the state of bladder, was interpreted as a sign of 'genital' sphincteric activity of the same circular smooth muscle.

Action Potentials↗
PubMed1991

Imidazo[1,2-a]pyridines. I. Synthesis and inotropic activity of new 5-imidazo[1,2-a]pyridinyl-2(1H)-pyridinone derivatives.

A series of 1,2-dihydro-5-imidazo[1,2-a]pyridinyl-2(1H)-pyridonones was synthesized and evaluated for positive inotropic activity, 1,2-Dihydro-5-imidazo[1,2-a]pyridin-6-yl-6-methyl-2- oxo-3-pyridinecarbonitrile (11a) hydrochloride monohydrate (E-1020) was found to be a potent and selective inhibitor of phosphodiesterase III and a long-acting, potent, orally active positive inotropic agent. Additional imidazo[1,2-a]pyridin-2-yl (3a), -3-yl (16), -7-yl (20) and -8-yl (24a) compounds were also prepared. Altering the pyridine substitution from the 2-position to the 6-position produced a 2-fold increase in the i.v. cardiotonic potency (ED50) from 52 to 23 micrograms/kg, while substitution at the 3-, 7- or 8-position reduced potency. In the 2-positional isomers, introduction of halogen groups enhanced the activity and 3-chloro-1,2-dihydro-5-(6-fluoroimidazo[1,2-a] pyridin-2-yl)-6-methyl-2(1H)-pyridinone (3u) was the most potent (i.v. ED50 11 micrograms/kg) in this series. E-1020 is presently under development for the treatment of congestive heart failure.

Animals↗
PubMed1991

Pharmacokinetics of a novel dopamine DA1 receptor agonist, E4101, and an improvement of its bioavailability in dogs.

Pharmacokinetic parameters of E4101,(-)-(3R,4R)-3-(2-chloro-3-hydroxyphenyl)- 4-(3,4-dihydroxyphenyl)-pyrrolidine hydrochloride, in plasma were determined in conscious beagles. E4101 was extracted from plasma using a Bond Elute C18 cartridge and determined by HPLC connected to a reverse phase ODS column and an electrochemical detector. After an i.v. administration of 1 mg/kg, the plasma level of E4101 decreased according to the three compartment model. The half lives of the alpha, beta and gamma phases were 1.3, 8.1 and 27 min, respectively. The mean residence time (MRT) and total clearance were 14.5 min and 78 ml/min/kg, respectively. When 3 mg/kg of E4101 were administered orally under fasting, E4101 in plasma reached the peak (Cmax: 22.4 ng/ml) 45 min after administration. The bioavailability was 3.6%. When 3 mg/kg of E4101 in combination with 15 mg/kg of ascorbic acid was orally administered in capsule, the area under concentration curve (AUC) was increased 7-fold compared with that in a matched control study. A combination with 15 mg/kg of tartaric acid, citric acid, L-aspartic acid or L-cysteine also increased the AUC, byt they were less effective than ascorbic acid. When 10 mg/kg of E4101 in combination with 25 mg/kg of ascorbic acid as a sustained-release dosage form using oily somisolid matrix orally administered to non-fasted beagles, the duration of effective plasma concentration (2 ng/ml plasma in i.d. administration) was 8.4 +/- 1.0 hr (mean +/- SE, n-4). The Cmax was 16.2 +/- 2.5 ng/ml.

Animals↗
PubMed1991

[Evaluation of CT-guided stereotactic hematoma aspiration in mild cases with putaminal hemorrhage].

Reported here is the effectiveness of surgical management in mild cases with putaminal hemorrhage (neurological grading 1 or 2, described by Kanaya, et al.). Ten cases were treated by CT-guided stereotactic hematoma aspiration (aspiration group), and another 10 cases were treated by only medical therapy (conservative group). The mean interval from the onset to operation was 7.2 days. In both groups, serial change in the motor function of the upper extremity was examined and the neuropsychological function was also evaluated at 2 weeks after onset. Perifocal low-density area around the hematoma was estimated on CT scan at 2 weeks after onset. Mean hemispheric cerebral blood flow (mCBF) was measured at 5-days, 2 weeks and 6 months after onset, respectively in each group. The activity of daily life (ADL) was evaluated at 6 months after onset. There was no statistically significant difference in age, neurological grading and CT findings on admission between the 2 groups. At 2 weeks after onset, no case had deteriorated in motor function in the aspiration group. On the other hand, 2 cases had deteriorated in the conservative group. The neuropsychological function was considerably improved in the majority of cases in the aspiration group. Perifocal low area was significantly narrow on CT scan in the aspiration group. At 2 weeks after onset, the mCBF of the affected side was 53.8 +/- 6.0 ml/100g/min in the aspiration group, whereas it was 42.0 +/- 5.7 ml/100g/min in the conservative group. This difference was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Ganglia Diseases↗
PubMed1991

[Prognostic value of spectral analysis of electroencephalogram in patients with severe head injury].

To determine the prognostic value of electroencephalogram (EEG) in patients with severe head injury, fifteen adult patients were examined for three months after trauma. All patients (age: 16-74 years old) remained comatose (Glasgow Coma Scale: less than 8) for more than 72 hours. Ten out of 15 cases were surgically treated. Barbiturates were not used in any patient for the sake of controlling the increased intracranial pressure. Three months after trauma, the clinical outcome of each patient was evaluated using Glasgow Outcome Scale (GOOD: good recovery/moderate disability, POOR: severe disability/persistently vegetative/dead). EEG was examined repeatedly for 3 months after trauma; 56 EEG recordings were performed on 15 cases. Each EEG recording was never for less than 12 hours and EEG was recorded from the bilateral parietal electrodes. Using EEG TREND MONITOR (NIHONKODEN), the spectral analysis of EEG was performed in five frequency bands (delta, theta, alpha-1, alpha-2, beta) and the EEG power of each frequency band was shown as the percentage of total EEG power (% FREQ BAND). The findings of each % FREQ BAND was classified into the following four groups. 1) slow-monotonous: The EEG power was comprised invariably and almost exclusively of low frequency bands (i.e. delta and theta), and the "slow-fast constant" which is the power of slow waves (delta and theta) divided by the power of fast waves (alpha-1, alpha-2, and beta) was stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[A case of hypertrophic cranial pachymeningitis].

A case of hypertrophic cranial pachymeningitis was reported. A 58-year-old female presented the symptoms of headache and vomiting. At the age of 27, she had suffered from tuberculosis. Neurological examination on admission revealed bilateral papilledema, bilateral hearing disturbance, right hypoglossal nerve palsy, ataxic gait, and bilateral intentional tremor. CT scan showed dilatation of the lateral and third ventricles, and compression of the fourth ventricle with marked enhancement of cerebellar tentorium. A ventriculoperitoneal shunt was installed bringing about improvement in bilateral papilledema, ataxic gait, and bilateral intentional tremor. One month later, ataxic gait and bilateral intentional tremor recurred, and monoparesis of the left upper extremity developed. MRI demonstrated hypertrophic dura mater in the posterior fossa and compressed cervical spinal cord. Decompressive surgery was performed bringing about remarkable clinical improvement. The pathological specimen showed thickening of the dura mater with concentric layers of dense fibrous tissue infiltrated with plasma cells. A diagnosis of hypertrophic cranial pachymeningitis was established. Three years later, the clinical features were found unchanged, but contrast enhancement of cerebellar tentorium had progressed markedly. Hypertrophic pachymeningitis is a uncommon disease. But it should be noted that intracranial involvement is very rare. The etiology, symptomatology, neuroradiology, and treatment are discussed and the literature is reviewed.

Dura Mater↗
PubMed1990

Influence of plasma glucose concentration on lumped constant of the deoxyglucose method: effects of hyperglycemia in the rat.

The lumped constant of the deoxyglucose method was determined by the steady-state, model-independent method in the brain of normal conscious rats with arterial plasma glucose concentrations varying from normoglycemia (i.e., 8 mM) to hyperglycemia (i.e., 31 mM). The lumped constant for brain was found to decrease very gradually with increasing arterial plasma glucose concentration from a value of approximately 0.45 in the midnormoglycemic range (i.e., 7-8 mM) to approximately 0.38 at 28-31 mM. 3-O-[14C]Methylglucose was used to assess the distribution of glucose within the brain structures in hyperglycemia; the results indicated that the glucose concentration, and therefore also the values for the lumped constant, remain relatively uniform in hyperglycemia with arterial plasma glucose concentrations as high as 34 mM. The values for the lumped constant for rat brain determined in the present studies were combined with those previously determined in this laboratory for hypoglycemia and normoglycemia by the same method to provide a single source for the values for the lumped constant to be used over the full range of arterial plasma glucose concentrations. In several rats the lumped constant for cephalic extracerebral tissues was also evaluated in parallel with those for the brain. The lumped constant for the cephalic extracerebral tissues was found to be about twice that for brain and to be unaffected by changes in arterial plasma glucose levels.

Algorithms↗
PubMed1990

The lumped constant of the deoxyglucose method in hypoglycemia: effects of moderate hypoglycemia on local cerebral glucose utilization in the rat.

The applicability of the [14C]deoxyglucose method for measuring local cerebral glucose utilization (lCMRglc) has been extended for use in hypoglycemia by determination of the values of the lumped constant to be used in rats with plasma glucose concentrations ranging from approximately 2 to 6 mM. Lumped constant values were higher in hypoglycemia and declined from a value of 1.2 at the lowest arterial plasma glucose level (1.9 mM) to about 0.48 in normoglycemia. The distribution of glucose, and therefore also of the lumped constant, was found to remain relatively uniform throughout the brain at the lowest plasma glucose levels studied. lCMRglc in moderate, insulin-induced hypoglycemia (mean arterial plasma glucose concentration +/- SD of 2.4 +/- 0.3 mM) was determined with the appropriate lumped constant corresponding to the animal's plasma glucose concentration and compared with the results obtained in six normoglycemic rats. The weighted average rate of glucose utilization for the brain as a whole was significantly depressed by 14% in the hypoglycemic animals, i.e., 61 mumols/100 g/min in hypoglycemia compared to 71 mumols/100 g/min in the normoglycemic controls (p less than 0.05). lCMRglc was lower in 47 of 49 structures examined but statistically significantly below the rate in normoglycemic rats in only six structures (p less than 0.05) by multiple comparison statistics. Regions within the brainstem were most prominently affected. The greatest reductions, statistically significant or not, occurred in structures in which glucose utilization is normally high, suggesting that glucose delivery and transport to the tissue became rate-limiting first in those structures with the greatest metabolic demands for glucose.

Algorithms↗
PubMed1990

[Computed tomography in diagnosis of diffuse axonal injury].

Diffuse axonal injury (DAI) has been described in instances of prolonged traumatic coma on the basis of the neuropathological findings, but the same findings are also found in patients with cerebral concussion. Experimental studies confirm that the quality of survivors following trauma is directly proportional to the amount of primarily injured-axon. When the injured axon lies in a widespread area of the brain, outcome for the patient is always poor. In a series of 260 severely head-injured patients, based on their poor outcome, 69 (27%) were diagnosed as DAI. Because of their relatively good outcome, eighty-two patients (32%) were classified into non-DAI group. The predominant CT finding of DAI patients was intraparenchymal deep-seated hemorrhagic lesion. This was observed in 28 patients (41%). Normal CT was also observed in 11 patients (16%). On the other hand, 8 of the non-DAI group (10%) manifested deep-seated lesions. Diffuse cerebral swelling (DCS) appeared in both groups in the same incidence. Subarachnoid hematoma in the perimesencephalic cistern (SAH (PMC] and intraventricular hematoma (IVH) were observed in 64% of the DAI group, and in 23% of the non-DAI group. The available evidence indicates that various types of hematoma seen in the deep-seated structures of the brain do not have an absolute diagnostic value, but the frequency of hematoma is thought to increase in proportion to the amount of injured-axon.

Adolescent↗
PubMed1990

Oscillatory potentials recorded from walls of anal canal and urethrae in dogs.

1. Oscillatory potentials were recorded from internal anal sphincters and from internal urethral sphincters in similarity and difference in their characteristics. similarity and difference in their characteristics. 2. Unexpected finding was the appearance of burst-and-pause alternation in male urethrae in contrast to continuous oscillation in female urethrae. 3. Stimulation experiments revealed that the internal anal sphincter was controlled by reciprocal spinal outflow; lumbar accrelation and sacral inhibition. But the recto-anal reflex, constantly observable in decerebrate dogs, was predominantly inhibitory, which was identical with sacral action. 4. The effect of ventral root stimulation upon urethral oscillation was 'identical' for lumbar and for sacral activations, even if it was excitatory or inhibitory, depending upon ongoing level of activity and upon stimulus parameters. Nevertheless, reciprocal activation between detrusor spike and urethral oscillation was observed during 'isometric voiding contractions'. The reason for this inconsistency was discussed.

Anal Canal↗
PubMed1989

Possible contribution of green tea drinking habits to the prevention of stroke.

Among 5910 nondrinking and nonsmoking women (of greater than or equal to 40 years of age) in a prefectural city of Sendai, and two villages of Taijiri and Wakuya in Miyagi prefecture, Japan, medical history of stroke was less frequently observed among those who took more green tea in daily life. No relation with tea drinking was observed for hypertension history. The uneven distribution of stroke history was detectable even after the effects of age, location of residence, and high salt intake were ruled out. The incidence of stroke and cerebral hemorrhage during a 4-year follow-up of the study population was twice or more times higher in those who took less green tea (less than 5 cups a day) than in those who took more (greater than or equal to 5 cups daily).

Adult↗
PubMed1989

[Simultaneous, multiple hypertensive intracerebral hematomas: report of 5 cases and review of literature].

Five cases of multiple hypertensive intracerebral hematomas which occurred simultaneously but in different locations were described in this report. The diagnoses of all five cases were established by computed tomography, and the location of the hematomas was as follows; case 1. bilateral putamen, case 2. bilateral thalamus and right parietal subcortex, case 3. cerebellum and left thalamus, cases 4 and 5. cerebellum and right putamen. These represented 0.7% of all the patients (679 cases) who suffered from hypertensive intracerebral hematoma and were admitted to our two institutions in the last five years. We also reviewed the other 11 cases which have been reported in literature, and the total 16 cases were analyzed with respect to clinical characteristics, pathogenesis of multiple hematomas, indication of operation and prognosis. 1. The age distribution had a peak in the 70's and was similar to that of single hematoma. 2. Sixteen cases had 34 intracerebral hematomas. Eleven cases had bilateral supratentorial lesions. Four cases had cerebellar and supratentorial lesions. The remaining had two supratentorial lesions ipsilaterally. The distribution of 34 hematomas (16 in cerebral basal ganglia, 10 in thalamus, 4 in cerebellum, 4 in cerebral subcortex and none in pons) was well correlated to the distribution of usual hypertensive intracerebral hematomas. 3. The clinical symptoms were characterized by severe consciousness disturbance and severe neurological deficits. Their outcome was poor. 4. As for the possible mechanism of simultaneous multiple hemorrhages, we suspected either that two or more primary bleedings occurred simultaneously in the different regions, or that a primary bleeding was followed a short time after by a secondary bleeding in the other site.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗