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Biomedical subjects

Y Shiokawa

Publications and source records attributed to Y Shiokawa.

At least 91 records · Page 5Linked to original sources
PubMed1994

Agents for the treatment of overactive detrusor. VI. Synthesis and pharmacological properties of acetamide derivatives bearing cyclic amines in N-substituents.

With the aim of improving of the efficacy and decreasing the side effects of oxybutynin (1), N-[(tetrahydro-3- or 4-pyridyl)methyl]-, N-(4-piperidyl)-, and N-(3- or 4-piperidylalkyl)-2-hydroxyacetamides (3a-n, 4a-g) and the related carboxamides (3o-r, 4h-k, 13', 17) were synthesized and evaluated for inhibitory activity against urinary bladder rhythmic contraction in rats and for mydriatic activity in rats. Some of these compounds were superior to oxybutynin in both inhibitory activity against bladder contraction and selectivity between inhibitory activity against bladder contraction and mydriatic activity. Among them, N-[(1,2,3,6-tetrahydro-4-pyridyl)methyl]- and N-[(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)methyl]-2-hydroxy-2,2- diphenylacetamide (3e, 3f) exhibited the most potent inhibitory activity against bladder contraction (ED30 = 0.005 and 0.003 mg/kg i.v., respectively). Judging from the effect of 3e on detrusor contraction in vitro in guinea-pigs, it appeared that the inhibitory activity of 3e against bladder contraction in vivo was related mainly to its inhibitory activity against detrusor contraction in vitro induced with carbachol (antimuscarine-like activity). The selectivity (20-fold) of 3e between inhibitory activity against bladder contraction and mydriatic activity was greatly superior to that (0.48-fold) of oxybutynin. Compound 3e was synthesized by debenzylation (method E or F) of the corresponding N-[[1-(4-methoxybenzyl)-tetrahydro-4-pyridyl]methyl] derivative (3k), which was prepared by acylation (method B) of the corresponding (tetrahydro-4-pyridyl)methylamine (7k) or by reduction (method D) of the corresponding pyridinium chloride (14k) with NaBH4.

Acetamides↗
PubMed1994

Agents for the treatment of overactive detrusor. VII. Synthesis and pharmacological properties of 2,3- and 3,4-diphenylcyclopentylamines, 2,3-diphenyl-2-cyclopentenylamines, and related compounds.

As part of our search for new agents for the treatment of overactive detrusor, 2,3- and 3,4-diphenylcyclopentylamines (3), 2,3-diphenyl-2-cyclopentenylamines (4), and related compounds (5 and 18) were synthesized and evaluated for inhibitory activity (i.v.) against urinary bladder rhythmic contraction in rats. Among them, some compounds involving N-tert-butyl-2,3-diphenyl-2-cyclopentenylamine (4b) exhibited inhibitory activity against bladder contraction superior to that of terodiline (2). Mydriatic activity (i.v.) of compound 4b in rats, an index of its side effects due to antimuscarinic activity, was found to be relatively weak in comparison with its inhibitory activity against bladder contraction. The pharmacological profile of 4b was examined in comparison with that of terodiline. Most of the objective amines (3, 4, 5) were synthesized by preparation of Schiff bases from the corresponding cyclic ketones (6, 7, 8) and amines in the presence of TiCl4 in CH2Cl2 and subsequent reduction with NaBH4 in the presence of MeOH in one pot (method A).

Amines↗
PubMed1994

Studies on nilvadipine. IV. Synthesis of deuteriated and optically active isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4- dihydropyridine-5-carboxylate (nilvadipine).

Nilvadipine, I, has already entered clinical use for the treatment of hypertension. In the process of the developing nilvadipine, we prepared the deuteriated analogue of I as an internal standard for the determination of I in human plasma by capillary column gas chromatography-negative-ion chemical-ionization mass spectrometer. Nilvadipine has an asymmetric center at the C-4 position of the dihydropyridine ring, and characterization of the optical isomers with regard to their activity and bioavailability is of interest. Thus, we synthesized both the enantiomers of I by optical resolution via the 5-carboxy derivative (3), which was previously prepared as one of the metabolites of I.

Antihypertensive Agents↗
PubMed1994

[Evaluation of inhibitory effect of isoflurane on the hypoxic pulmonary vasoconstriction response in dogs].

The effect of isoflurane on hypoxic pulmonary vasoconstriction (HPV) was examined using the separately ventilated left lower lobe lung model in dogs. When the HPV was induced with anoxic gas ventilation of the left lower lobe, the magnitude of HPV inhibition by isoflurane of 2 MAC was predominant, as assessed by the index of pressure-flow curve which is a novel indicator of pulmonary vascular tone in the left lower lobe. However, isoflurane 2 MAC attenuated the HPV by only 16%, as assessed by indices of the changes in left lower lobe blood flow rate and PaO2. This weak HPV inhibition, as shown by the latter parameters, may result from the net effect of isoflurane-induced HPV inhibition and secondary HPV enhancement due to decreases in cardiac output and pulmonary arterial pressure by isoflurane. However, none of the parameters showed inhibition of HPV when the HPV was induced by collapse of the left lower lobe. This discrepancy in the results may be caused by a lack of isoflurane reaching the hypoxic lobe when the HPV is induced with atelectasis. These results show that potency of HPV inhibition with isoflurane depends on the method of induction or evaluation of HPV, and that inhibition of HPV response with isoflurane at clinical concentrations is negligible in an atelectasis-induced HPV, in which no isoflurane is directly reaching the hypoxic lobe.

Animals↗
PubMed1994

[Practical CT classification for thalamic hemorrhage: relationship between localization of hematoma and prognosis].

It is not easy to predict functional outcome in patients with acute-stage thalamic hemorrhage. We analysed 100 cases of hypertensive thalamic hemorrhage less than 4 cm in diameter, and devised a practical CT classification for predicting the patients' prognoses. On an axial CT scan at the level of the pineal body, four lines were drawn as follows: line (a) between the lateral edge of the anterior horn and the midpoint of the third ventricle; line (b) vertical line to the sagittal line from the midpoint of the third ventricle; line (c) between the lateral edge of the trigone and the midpoint of the third ventricle; line (d) between the lateral edge of the anterior horn and the lateral edge of the trigone. The location of hematoma was divided into three types according to lateral extension as follows: type A (anterior type), center of hematoma located between line (a) and line (b); type P (posterior type), center of hematoma located between line (b) and line (c), and external margin of hematoma localized medial to line (d); type PL (postero-lateral type), center of hematoma located between line (b) and line (c), and showing lateral extension beyond line (d). Then, the correlation between hematoma location and severity of motor paresis at onset and its prognosis was investigated. Severe hemiparesis (MMT: 0-2) was observed in 15.3% of patients with type A, 21.8% with type P, and 59.3% with type PL hematoma in the acute stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Reoperation for transposition of the great arteries: mid-term results and reoperation after arterial switch operation].

The arterial switch operation for transposition of the great arteries is now widely accepted as the therapeutic method of choice. As of December 1993, a total of 162 patients underwent the arterial switch. There were 100 patients with transposition and intact ventricular septum, 48 with a ventricular septal defect, 14 with ventricular septal defect and arch anomalies (coarctation: 11, interruption: 3). Early and late mortality were 3.7% (6 patients) and 4.5% (7 patients), respectively. Postoperative pulmonary stenosis (> 30 mmHg) was noted in 33 patients (22%), aortic regurgitation (> mild) in 20 (13%), supravalvular aortic stenosis (> 20 mmHg) in 5 (3%) and mitral regurgitation (> mild) in 5 (3%). Reoperation was performed in 27 patients with no mortality. Mean interval between the switch and the reoperation was 30 months. Twenty-three patients with pulmonary stenosis underwent patch plasty of pulmonary artery. Two children with severe aortic regurgitation underwent aortic valve replacement. Two patients who had undergone one-staged repair for interruption complex were reoperated due to supravalvular aortic stenosis and pulmonary stenosis. Actuarial survival and freedom from reoperation at 9 years were 90% and 69%, respectively.

Aortic Valve Stenosis↗
PubMed1993

The problem of macular sparing after unilateral occipital lesions.

Whether or not unilateral occipital damage produces sparing of central vision, namely macular sparing, is controversial. We tested two subjects with left occipital lesions by means of fundus perimetry combined with fundus image analysis. This method made it possible to measure the distance of the stimulus projected on the retina from the foveal centre defined as the centre of the foveal reflex. The results indicated that macular sparing, if it exists, must be less than 0.4 degree wide. Two of the four eyes during the stimulus presentation often but not always showed eccentric fixation of a small magnitude, whose mean was less than 0.6 degree from the foveal centre in the right hemiretina.

Cerebral Infarction↗
PubMed1993

Brain stem haemorrhage during transsphenoidal surgery. Possible risk of the manoeuvre of increasing the endexpiratory pressure in a case of pituitary adenoma associated with dural arteriovenous malformation. Case report.

The authors report a case of pituitary adenoma associated with dural arteriovenous malformation (AVM), which caused brain stem haemorrhage during transsphenoidal surgery. The manoeuvre of increasing the endexpiratory pressure in order to push the suprasellar component of the adenoma down to the sella turcica could be the reason of this bleeding. The authors therefore recommend that in cases of such a combination any manoeuvres which are likely to increase the intracranial venous pressure or otherwise affect the intracranial pressure, are avoided. The dural AVM spontaneously regressed after haemorrhage.

Adenoma↗
PubMed1993

Effect of spantide, a substance-P antagonist, on cerebral vasospasm in primates.

Experimental SAH in the squirrel monkey induces an angiographically demonstrable late spasm of about 23% at six days post subarachnoid haemorrhage (SAH). The late spasm is associated with a generalized reduction in cerebral blood flow (CBF) of about 30%. Intracisternal administration of the substance P (SP) antagonist spantide two hours and three days post SAH significantly reduces the degree of late spasm and also decreases the degree of CBF reduction. The findings suggest that SP is involved in the development of both angiographical spasm and CBF changes post SAH.

Analgesics↗
PubMed1993

Cerebral blood flow and glucose metabolism in the squirrel monkey during the late phase of cerebral vasospasm.

A double-isotope autoradiography technique was used to evaluate cerebral blood flow (CBF) and cerebral glucose metabolism (CMRglu) during the late phase of vasospasm in a squirrel monkey subarachnoid haemorrhage (SAH) model. Cisternal blood injections induced both global and focal changes in CBF and CMRglu six days following SAH, the timepoint of maximal late spasm in this model. There was a global decrease in CBF of about 30% accompanied by an increase in deoxyglucose uptake of about 50%. Four of seven animals also had foci with flow decreased to 40% of control and deoxyglucose uptake increased to 300% of control. There was an altered but still present interdependence between flow and metabolism post SAH.

Animals↗
PubMed1993

Revised technique of cardiopulmonary bypass in one-stage repair of interrupted aortic arch complex.

Twenty infants with interrupted aortic arch associated with various intracardiac anomalies underwent primary complete repair using pulsatile high-flow cardiopulmonary bypass with a short period of circulatory arrest. Age at repair ranged from 11 to 126 days (mean age, 43 days). Weight ranged from 2.2 to 5.5 kg (mean weight, 3.4 kg). Associated cardiac lesions included ventricular septal defect (14 patients), truncus arteriosus (3), transposition of the great arteries (2), and aortopulmonary window (1 patient). Left ventricular outflow tract obstruction was relieved in 2 patients. The aortic arch was reconstructed with a polytetrafluoroethylene graft in 7 patients and by direct anastomosis in the most recent 11 patients. An arterial cannulation method has been devised to facilitate direct anastomosis between the ascending aorta and the descending aorta, to lessen circulatory arrest time, and to prevent dangerous laceration and postoperative narrowing of the thin, small ascending aorta at the cannulation site. Two patients died, a surgical mortality rate of 10%. There has been one late death, which was due to severe truncal valve insufficiency. The other patients are doing well with a mean follow-up of 3 years 6 months. Restenosis of the direct anastomosis has not been noted in any patient. However, subaortic stenosis with pressure gradients of 30 to 40 mm Hg developed in 3 patients. In conclusion, one-stage repair including direct anastomosis for the aortic arch reconstruction and repair of all coexisting intracardiac defects is thought to be the treatment of choice.

Anastomosis, Surgical↗
PubMed1993

Effect of sevoflurane on hypoxic pulmonary vasoconstriction in the perfused rabbit lung.

BACKGROUND: In vitro studies have shown that isoflurane, enflurane, and halothane inhibit the hypoxic pulmonary vasoconstriction (HPV) with essentially the same potency. The aim of this study is to compare the effects of sevoflurane and isoflurane on HPV in constant-flow perfused rabbit lungs. METHODS: Constant-flow perfused lungs from Japanese white rabbits were tested. The lungs were divided into three groups: isoflurane alone (n = 6), sevoflurane alone (n = 6), and sevoflurane with ibuprofen pretreatment (n = 6). Baseline HPV responses were measured as the pulmonary arterial pressure increased after changing inspired oxygen concentration from 95% for 15 min to 3% (with 5% CO2) for 5 min without anesthetic administration. Next, three different concentrations of anesthetics were added to the inspired gas for 15 min in random order. The HPV response in the presence of anesthetic was expressed as a percentage of the pressor response in the absence of anesthetics, and dose-response relationships were calculated using the nonlinear least-squares method. RESULTS: Isoflurane and sevoflurane both depressed the HPV response in a dose-related manner. The half-inhibition values (ED50) of HPV with isoflurane and sevoflurane were 0.85 +/- 0.22 MAC and 1.00 +/- 0.12 MAC (mean +/- SD), respectively, and were not statistically different. Ibuprofen pretreatment did not alter ED50 and slope of dose-response curve, although the absolute value of pressor response in the sevoflurane group with ibuprofen pretreatment was greater than that in the sevoflurane alone group at every concentration of sevoflurane. CONCLUSIONS: Sevoflurane inhibits the HPV response in a dose-related manner, and its potency is similar to that of isoflurane in vitro. Cyclooxygenase products do not mediate the inhibition of HPV by sevoflurane.

Anesthetics↗
PubMed1993

Agents for the treatment of overactive detrusor. IV. Synthesis and structure-activity relationships of cyclic analogues of terodiline.

A series of pyrrolidine derivatives were synthesized and examined for inhibitory activity on detrusor contraction in vivo. Among those compounds, 5,5-dimethyl-2-(2,2-diphenylethyl)-3-isopropylidenepyrrolidine+ ++ hydrochloride (41.HCl), 2-(2,2-di(4-fluorophenyl)ethylene)-5,5-dimethyl-3-isopropylidenepyrro lidine hydrochloride (42.HCl), (+)-5,5-dimethyl-2-(N,N-diphenylaminomethyl)-3-isopropylidenepy rrolidine hydrochloride (+)-(43a.HCl), (-)-5,5-dimethyl-2-(N,N-diphenylaminomethyl)-3-isopropylidenepy rrolidine hydrochloride (-)-(43a.HCl), and 2-(N,N-di(4-fluorophenyl)aminomethyl)-5,5-dimethyl-3-isopropylidenepy rrolidine methanesulfonate (43b.MsOH) showed stronger inhibitory activity on detrusor contraction than terodiline.

Animals↗
PubMed1993

Cerebrovascular changes following administration of gammaglobulins against substance P or calcitonin gene related peptide in monkey with subarachnoid haemorrhage.

Cerebrovascular changes after intrathecal (ith) administration of gammaglobulins against substance P (SP) or calcitonin gene-related peptide (CGRP) were investigated before and following a simulated subarachnoid haemorrhage (SAH) in the squirrel monkey. The SAH was produced by injection of homologous blood into the interpeduncular fossa and the cisterna magna. The gammaglobulins were given both prior to the blood injections and daily in 5 days post-SAH. The effect of the gammaglobulins was examined by angiography pre-SAH and at 10 min and at 6 days post-SAH, i.e. the time points for maximal acute and late spasm in the present model. Cerebral blood flow (CBF) was measured under general anesthesia at day 6 post-SAH with an autoradiographic technique. Five of nine animals treated with CGRP antigammaglobulin died from respiratory failure. Four animals received SP antigammaglobulin and two control animals received normal globulin. SP antigammaglobulin per se had no effect on baseline arterial diameter, while CGRP antigammaglobulin significantly reduced the diameter of the arteries. SP antigammaglobulin prevented the occurrence of acute spasm and significantly reduced the degree of late spasm. Moreover, the reduction in CBF noted in the control SAH animals was significantly reduced. In contrast, CGRP antigammaglobulin treatment had no effect on the degree of spasm and did not cause any change in CBF as compared to controls. The finding that CGRP but not SP antigammaglobulin significantly reduces the arterial diameter in conjunction with our previous demonstration that a post-, but not preganglionic trigeminal lesion reduces the baseline arterial diameter, indicates that CGRP could be the transmitter involved in a peripheral axon reflex. The function of SP might be as a neurotransmitter conveying information to the brainstem. The transmitter role is supported by the effect of SP antigammaglobulin impairing SP containing neurons and, in that way, mimicking a bilateral trigeminal rhizotomy.

Analysis of Variance↗
PubMed1993

Intramuscular metastasis of carcinoma.

Four cases of intramuscular metastasis of carcinoma are reported. The preoperative clinical diagnosis of all four cases was soft-tissue sarcoma. Definitive diagnoses, made by open biopsy, were uterine carcinoma, gastric carcinoma, lung carcinoma, and hypopharyngeal carcinoma. All patients died from lung, liver, or brain metastasis several months after open biopsy despite surgery, chemotherapy, or radiation therapy. Case reports of macroscopic metastases to muscle are rare, and the authors report four such cases experienced during a 15-year period.

Adenocarcinoma↗