Biomedical subjects

Y Sakuma

Publications and source records attributed to Y Sakuma.

At least 145 records · Page 8Linked to original sources

PubMed1991

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist. Effects on microvascular permeability, hypotension and nephrosis.

The effects of a newly synthesized platelet-activating factor (PAF) antagonist, (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123, CAS 131614-02-3) on microvascular permeability, systemic hypotension and nephrosis were investigated. E-6123 inhibited PAF injection-induced microvascular permeability (edema) in guinea pigs after oral administration at 3 micrograms/kg. The inhibitory effects of E-6123 were very potent compared to those of other PAF antagonists. E-6123 reversed PAF and/or endotoxin injection-induced hypotension in rats after intravenous administration at 3 micrograms/kg. The increase in urinary protein excretion of rats in which nephrosis had been induced by intraperitoneal injection of aminonucleoside was not inhibited by oral administration of E-6123 at 10 mg/kg/d.

Animals↗

PubMed1991

Activity of a novel thienodiazepine derivative as a platelet-activating factor antagonist in guinea pig lungs. Effects on platelet-activating factor and allergen induced eosinophil accumulation.

Platelet-activating factor (PAF) inhalation in guinea pigs caused a significant increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). Oral administration of (S)-(+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] [1,2,4]triazolo[4,3-a][1,4]diazepine (E-6123), a novel PAF antagonist, at the dose of 100 micrograms/kg completely inhibited the PAF-induced eosinophil accumulation. Antigen inhalation in passively sensitized guinea pigs caused a significant increase in lung contents of PAF at 5 min, and accumulation of eosinophils in the bronchi 1 and 2 days thereafter, E-6123 inhibited the antigen-induced eosinophil accumulation and the maximum inhibition was approximately 65%. On the other hand, methylprednisolone completely inhibited the antigen-induced eosinophil accumulation. The results suggest that PAF is a potent attractant of eosinophils and is involved in antigen-induced eosinophil infiltration into bronchi. The results also suggest that E-6123 may be of therapeutic value in the treatment of asthma exhibiting eosinophil recruitment in airways.

Aerosols↗

PubMed1991

[Influence of location for jugular venous blood sampling to cerebral circulatory index (CCI)].

When cerebral circulatory index (CCI) expressed as inverse of arterial-jugular venous oxygen content difference is measured, venous sampling at the internal jugular bulb needs to be done in order to avoid mixture with extra-cerebral perfusion blood. To estimate the validity of this point, difference of values calculated with blood obtained simultaneously at the jugular superior bulb, the inferior region and the cerebral sinus were examined in monkeys. As a result, no significant differences were found to result from location of the sampling, and significant correlation between PaCO2 and CCI was recognized. These findings supported the idea that CCI reflects the cerebral blood flow due to PaCO2 changes.

Animals↗

PubMed1991

Pancreatic pseudocyst in the left hepatic lobe: a report of two cases.

The ultrasound and computed tomographic imaging features in a rare pancreatic pseudocyst of the liver are described in two patients. The pseudocysts occurred in the left lobe in both cases, one after a traumatic injury and the other after alcoholic pancreatitis. The possible topographical sequences with which pancreatic secretions entered the left hepatic lobe to form a cyst are discussed.

Adult↗

PubMed1990

Estrogen-induced suppression of female rat forebrain neurons with axons to ventral midbrain.

In estrogen-treated and non-treated ovariectomized female rats under urethan anesthesia, 278 neurons were antidromically identified in the medial preoptic and other basal forebrain areas by electrical stimulation of their terminals in the ventral tegmental area. Responses from the estrogen-treated rats had a significantly higher threshold, longer latency and absolute refractory period than those from the non-treated rats. Estrogen may decrease excitability of the preoptic axons along its length.

Action Potentials↗

PubMed1990

Hydrolysis and acyl migration of a catechol monoester of L-dopa: L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine.

Hydrolysis and acyl migration studies on L-3-(3-hydroxy-4-pivaloyloxyphenyl)alanine (1, NB-355), which produced long-lasting plasma L-dopa levels after oral dosing, have been conducted. Compound 1 exists as pure 4-O-pivaloyl-L-dopa in the solid state, but it converts rapidly to a mixture of the 3- and 4-O-isomers in solution. The rate of acyl migration increased with increases in pH and temperature, and the content of the 4-O-isomer in the equilibrium state was 53-59%. The hydrolysis rate of 1 to L-dopa (6) also increased with increases in pH and temperature, and accelerated steeply at neutral and alkaline pH. The rapid hydrolysis at neutral pH was not observed with O-pivaloyl-L-tyrosine (3), di-O-pivaloyl-L-dopa (4), or L-dopa methyl ester (5). Because of this chemical lability, 1 was hydrolyzed in rat plasma far faster than the other tested catechol esters. However, in rat intestinal homogenate at pH 6.0, 1 was hydrolyzed at the slowest rate among the tested esters, predominantly by a diisofluorophosphate (DFP)-sensitive esterase. Thus, 1 showed a unique in vitro profile on hydrolysis and acyl migration due to the existence of a neighboring hydroxyl group. The stability of 1 in the intestine might be essential for the long-lasting plasma L-dopa profile after oral dosing of 1.

Acylation↗

PubMed1990

Effects of a novel PAF antagonist, E6123, on PAF-induced biological responses.

E6123 is a new member of the benzodiazepine class of PAF antagonists. Although it has similar activity in vitro to the two representative antagonists WEB2347 and Y24180, in vivo it is far more active than these compounds. Thus E6123 was effective in inhibiting dose-dependently PAF-induced bronchoconstriction when administered orally or intravenously (IC50 1.0 and 1.3 micrograms/Kg, respectively, at 3 hr), and had a minimum effective dose of 10 micrograms/Kg and 3 micrograms/Kg, respectively, against PAF-induced hematoconcentration and edema at 3 hr after oral administration. Furthermore, E6123 protects mice from PAF-induced death dose-dependently (ED50 7 micrograms/Kg at 3 hr). In conclusion, E6123 should prove valuable in pharmacological and clinical research into the roles of PAF, and in therapy of diseases such as asthma, in which PAF is assumed to play a pathological role.

Animals↗

PubMed1990

Effects of a novel PAF antagonist, E6123, on passive anaphylaxis.

E6123 inhibited antigen-induced bronchoconstriction, the development of bronchial hyperreactivity and eosinophil infiltration in the airway in passively sensitized guinea pigs and protected mice from anaphylactic death. The inhibitory effects of E6123 on anaphylactic response were very potent compared with those of WEB 2347 and Y-24180.

Anaphylaxis↗

PubMed1990

Involvement of leukotriene C4 in PAF-induced death in mice.

The role of leukotrienes (LTs) in the pathogenesis of platelet-activating factor (PAF)-induced death in mice was reinvestigated, since previously reported results are in conflict. A novel 5-lipoxygenase inhibitor, E6080, and a leukotriene antagonist, LY17883, protected mice from PAF-induced death in a dose-dependent manner, while the well-known 5-lipoxygenase inhibitor, AA861, was less effective than E6080. After the intravenous injection of PAF in mice, immunoreactive leukotriene C4 (i-LTC4), which was co-eluted with authentic LTC4 in HPLC, was significantly increased in bronchoalveolar lavage fluid (BALF). Oral administration of E6080 suppressed the increase in i-LTCM4. The results suggest that LTs may play an important role in PAF-induced lethality in mice.

Acetophenones↗

PubMed1990

Estrogen-induced modulation of hypothalamic osmoregulation in female rats.

Estrogen treatment of ovariectomized female rats for a week decreased plasma osmolality from 294 to 278 mosmol/kgH2O, but recordings from the whole animal preparation under urethan anesthesia failed to detect any change in the activity of 76 vasopressinergic neurons in the supraoptic nucleus (SON) of the hypothalamus. In brain slice preparations, neuronal discharge of 74 presumed vasopressinergic SON cells increased linearly as the osmolality of the perfusate was increased from 278 to 320 mosmol/kgH2O, each 10 mosmol/kgH2O fraction corresponding to a 0.7-Hz change. This osmolality-neuronal activity relationship was similar in the slices taken from the estrogen-treated and the control ovariectomized animals, except that the neurons in the former fired twice as frequently as those in the control throughout the osmolality range. This difference explains the estrogen-induced decrease in the osmolality threshold to elicit antidiuresis and the resultant water retention in estrogen-treated animals. It was reasoned that the estrogen-induced neuronal activation was offset by the decreased plasma osmolality in the animal as a whole.

Animals↗

PubMed1990

Cleavage line patterns of the skin in the horse.

In 6 equine specimens of both sexes, the morphological features of the cleavage lines of the skin over the entire body were examined using a metal probe with a sharp conical point. Wounds were produced on the skin with the probe and painted with Chinese white or Indian ink. The direction of running of the cleavage lines was determined from their relationship to the long axis of each region or area of the physical structure. The cleavage lines of the head and face revealed a fixed pattern in all specimens. They were similar to those of equine fetuses of 6 to 7 months of age. A transverse pattern was found on the skin of the neck, trunk (abdomen), roots of the ear and tail, and external genital labium, except in some localized areas. The cleavage lines of the free extremities of the appendages already displayed a strikingly longitudinal pattern. A horizontal pattern was found in the middle costal region. It was clearer in the adult horse than in the equine fetus. The cleavage lines were annular in arrangement on the skin around the nares, eyes, and preputial orifice. They showed a convergent pattern on the skin of the metacarpal and metatarsal calcars, the umbilicus and anus. Some aspects of the skin tension were compared between the horse and certain other animals.

Age Factors↗

PubMed1990

[A case of adenocarcinoma in the renal pelvis and urinary bladder in a patient with chronic renal failure].

The patient was a 61-year-old male who had undergone right nephrectomy for nephrolithiasis 35 years before. He had been on hemodialysis for 6 years for chronic renal failure caused by left renal staghorn calculus and hydronephrosis. He was admitted to our hospital because of macroscopic hematuria and sense of residual urine which had persisted for 3 months. Cystoscopic examination showed an extensive papillary tumor in the urinary bladder, which histologically was an adenocarcinoma. Giant left hydronephrosis associated with staghorn calculus noted by KUB and CT scan. Total cystectomy, intraoperative radiotherapy, and left nephrostomy were performed under the diagnosis of adenocarcinoma of the urinary bladder and left hydronephrosis. The bladder tumor was found to be a mucinous adenocarcinoma. The patient died from a cerebral hemorrhage on the 17th postoperative day. At autopsy, tumors were found in the pelvis of the left kidney and the middle and lower regions of the ureter, which were adenocarcinoma like the bladder tumor. Adenocarcinoma occurring simultaneously in the renal pelvis and bladder has not been previously reported to our knowledge, in Japan or elsewhere.

Adenocarcinoma, Mucinous↗

PubMed1990

Pharmacological activities of a novel thienodiazepine derivative as a platelet-activating factor antagonist.

(S)-(+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11- dimethyl - 2,3,4,5 - tetrahydro - 8H - pyrido[4',3':4,5] thieno[3,2-fl-[1,2,4]triazolo]4,3-a][1,4]diazepine (E-6123) is a newly synthesized platelet-activating factor (PAF) antagonist. The effects of E-6123 on in vitro and in vivo PAF-induced responses were investigated. The IC50 values of E-6123 on 3H-PAF binding to human and guinea pig platelets were 2.7 and 3.0 nmol/l, respectively, and those on PAF-induced platelet aggregation in platelet-rich plasma of human, guinea pig and beagle dog were 10.1, 14.7 and 16 nmol/l, respectively. Oral administration of E-6123 at 3 and 10 micrograms/kg to dogs inhibited ex vivo PAF-induced platelet aggregation in a dose-dependent manner. In guinea pigs, E-6123 at 3 micrograms/kg completely inhibited ex vivo PAF-induced platelet aggregation up to 8 h and the inhibition was still significant at 24 h after administration. Occupancy of the platelet PAF receptor by E-6123 at 3 h and 24 h after administration amounted to 80% and 56%, respectively. Bronchoconstriction induced by PAF injection in guinea pigs was inhibited dose-dependently by oral or intravenous administration of E-6123 at similar doses. The IC50 value of E-6123 at 3 h after oral administration was 1 microgram/kg. Oral administration of E-6123 at 3 micrograms/kg inhibited the bronchoconstriction by more than 90% up to 8 h. Hemato-concentration induced by PAF injection in guinea pigs was inhibited by oral administration of E-6123 at 10 micrograms/kg. E-6123 also protected mice from PAF injection-induced death in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1990

[Dentist's understanding on dental anesthesiology--on the basis of a questionnaire on post-graduation study].

We set out a questionnaire for 400 participants of the seminar, to investigate the thoughts of dental practitioners and dentists on duty with regard to the post-graduation study and training in particular, to dental anesthesiology. The results obtained were as follows. 1. Almost all of the dental practitioners felt necessary to receive the post-graduation study and training to brush up their techniques. 2. The dental practitioners felt defective in actual techniques prepared by post-graduation trainings now under way, and they desired a particular training in an actual technique specific to an emergency therapy. 3. Seminars for re-education they desired to attend were those related to anesthesia in majority, followed by prosthetics, maintenance and periodontosis, orthodontics, and surgery, implantodontics, and pedodontics. 4. Major curriculums of anesthesiology they desired to receive were systemic management, resuscitation, how to apply the first-aid medicine, and treatment for shock states. The number of those participants who desired to receive these curriculums was help or above of all members, followed by those in dental psychosomatic disease, treatment for senile patients and acupuncture anesthesia. 5. It was unexpected that those who had been aware of the concept of authorized dental anesthesiologist were confined to 54% of the participants. This led us to consider that clinical dentist should be re-educated regarding the system for authorized anesthesiologist. 6. Major participants answered nothing with regard to the advocated curriculums we questioned, so that it was postulated that none felt unsatisfactory of the advocated curriculums at present.

Anesthesia, Dental↗

PubMed1990

[Judgement on students' exercise for resuscitation using a manikin for CPCR exercise (1st report)].

We performed the training for resuscitation using dental students and used a manikin for CPCR Exercise before and after the training to investigate the result obtained. The results were as follows. 1. Although cases in which too much or too little ventilation in amount was judged showed no significant changes before and after the training, those judged too much in ventilation amounted to approx. 1/5 and those judged too little were approx. 1/2 of the total subjects. This suggests that it is preferable to instruct the students to maintain sufficient ventilation when allowing them to exercise artificial breathing of CPCR. But the instruction is somewhat difficult to take because inhibition of gastric distention should be taken into account. 2. Although no changes were shown before and after the training by cases judged too deep in the depth of thoracic oppression, the number of those cases amounted to approx. 4/5 of the total subjects. Cases judged too shallow in depth of thoracic oppression, on the other hand, were significantly decreased from approx. 4/5 before training to approx. 2/3 after training, suggesting that improvement of the shallow oppression initially made is easy rather than to improve the oppression unduly deepened. Accordingly, it appears effective for students to avoid undue oppression when they are trained. 3. Thoracic oppression at a correct position was increased significantly to approx. 1/5 of the total cases, although most of the subjects were in error to choose a correct position for thoracic oppression before training.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary Resuscitation↗

PubMed1989

Brain aromatase activity and behavioral consequences in the male rat treated in utero with 4-hydroxy-androstenedione.

Pregnant female rats were given daily injections of a potent aromatase inhibitor, 4-hydroxy-delta 4-androstenedione (4OHA), throughout the latter half of the pregnancy (days 11 to 22; the day of insemination was designated as Day O) and male fetuses and pups were obtained. Control animals were male offspring of mothers treated with oil vehicle. When measured by the tritium-water method, significant reductions in the aromatase activity were detected in the hypothalamic and preoptic continuum (HPOA) of the male fetuses and pups, over a period from day 16 of the pregnancy until a day after birth. All parturitions in the experimental as well as control animals occurred on day 22 of the pregnancy. Behavioral and anatomical consequences of the prenatal treatment were examined in adulthood. When mounted by stud male rats, the male litters of the 4OHA-treated mother showed lordosis at a significantly higher frequency both in terms of the number of positive test sessions (each consisted of a 20-min period in which the subject showed lordosis at least once) and the lordosis quotient (percent lordosis occurrence per 10 mounts). When placed with receptive female rats, the experimental animals were no less active in mounting or ejaculating than the control. No significant difference existed between the experimental and control animals in the weight of the testes or the accessorial genitalia, or the serum testosterone levels. Partial but significant intervention of behavioral defeminization of the brain was associated with decreased HPOA aromatase activity during the prenatal period.

Androstenedione↗

PubMed1989

[Clinical study on the prognosis of complete denture wearers covering 10 years. 4. Masticatory efficiency].

The purpose of this study was to estimate masticatory efficiency of complete denture wearers. The subjects were 72 patients, treated before 5-10 years at students' clinic of Tsurumi University, School of Dental Medicine. The masticatory efficiencies with peanuts and Kamaboko were calculated. Results 1. The mean masticatory efficiency with peanuts for 63 patients was 35.8%, and with Kamaboko (steamed fishpast) for 64 patients was 94.5%, in comparison with natural dentition. 2. The mean masticatory efficiency with peanuts was 124.3%, and with Kamaboko was 99.6%, for complete denture wearers. 3. Comparing the measured value of masticatory efficiency with 5 to 10 years wearing period, there was significant difference in the masticatory efficiency between peanuts and Kamaboko. 4. There was significant difference in the masticatory efficiency with peanuts between the group needed new denture and the group not needed but there was not significant difference with Kamaboko.

Denture, Complete↗

PubMed1989

[Inhibitory effect of AA-673 eye drops on ocular provocation for Japanese cedar pollinosis].

The inhibitory effect of 0.25% AA-673 eye drops on histamine release in tears was examined by an ocular provocation test with antigen in 11 patients with Japanese cedar pollinosis during the off-season. AA-673 eye drops were administered into the right eye, while the left eye was given placebo eye drops. Five minutes later, a cedar antigen solution at 1:20 w/v was applied to the eyes. Levels of histamine in collected tears were determined by radioimmunoassay. Histamine levels in tears before, and 5 min and 10 min after provocation amounted to 0.2 +/- 0.2 ng/ml, 1.2 +/- 1.3 ng/ml and 1.3 +/- 1.6 ng/ml, respectively, while they were 0.2 +/- 0.2 ng/ml, 3.4 +/- 2.4 ng/ml and 3.6 +/- 3.6 ng/ml in the placebo-treated eyes at the same time points, showing a significant inhibitory effect of the drug on histamine release in the eyes treated with AA-673 (p less than 0.01 at 5 min; p less than 0.05 at 10 min). Inhibition rates of AA-673 eye drops on histamine release were 73.0% at 5 min and 69.6% at 10 min after provocation, indicating the excellent effect of this preparation in inhibiting histamine release. From the above findings it is considered that 0.25% AA-673 eye drops are an effective new therapeutic agent for Japanese cedar pollinosis.

Adolescent↗