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1.
The electrophysiological actions of SUN 1165 on isolated guinea pig atrial and papillary muscles, canine Purkinje fibers, and rabbit sinoatrial node were studied using standard microelectrode techniques. SUN 1165 in low (10(-7) g/ml) concentration had little effect on any of the action potential parameters measured. Intermediate (10(-6) g/ml) concentration of the compound shortened the duration of action potential of canine Purkinje fibers and increased ratio of the effective refractory period to the duration of action potential at 90% repolarization in guinea pig atrial muscles. At high (10(-5) g/ml) concentration, the compound reduced the maximum rate of rise of phase 0 in guinea pig atrial, papillary muscles, and canine Purkinje fibers, though the change in the latter was not statistically significant, and also decreased the action potential amplitude in guinea pig atrial muscles and canine Purkinje fibers. At all concentrations (10(-7)-10(-5) g/ml) tested, the compound exerted little effect both on spontaneous action potentials in rabbit sinoatrial node cells and on Ca2+-mediated slow responses in partially depolarized guinea pig papillary muscles. These results indicate that SUN 1165 may selectively inhibit cardiac sodium channels and is likely to be of value in correcting not only ventricular but also supraventricular tachyarrhythmias. 相似文献
2.
Effects of the new potassium channel opener JTV-506 on coronary vessels in vitro and in vivo 总被引:1,自引:0,他引:1
The vascular effects of JTV-506 ((-)-(3S,4R)-2.2-bis(methoxymethyl)- 4-[(1,6-dihydro-l-methyl-6-oxo-3-pyridazinyl)amino]-3-hydroxychroman+ ++-6- carbonitrile hemihydrate, CAS 170148-29-5), a new potassium channel opener, was evaluated in isolated coronary arteries and anesthetized dogs. JTV-506 (1 nmol/l-3 mumol/l) produced a concentration-dependent relaxation in porcine isolated epicardial large coronary arteries precontracted with KCl (30 mmol/l), phenylephrine (3 mumol/l), histamine (3 mumol/l), serotonin (5-HT; 300 nmol/l), prostaglandin F2 alpha (PGF2 alpha; 10 mumol/l), U-46619 (100 nmol/l), endothelin-1 (ET-1; 30 nmol/l) and Bay K-8644 (100 nmol/l). JTV-506 was 2.5-8.5 and 13.3-81.5 times more potent than levcromakalim (CAS 94535-50-9) and nicorandil (CAS 65141-46-0), respectively, but was less potent than nifedipine (CAS 21829-25-4). JTV-506 and levcromakalim produced almost a complete relaxation in arteries precontracted with various kinds of vasoconstrictor, except for KCl. In contrast, nifedipine produced about 80-90% relaxation in arteries, precontracted with PGF2 alpha, U-46619 and ET-1. Thus, this potassium channel opener can be characterized as an agonist-nonselective vasorelaxant. The relaxing effects of JTV-506 and levcromakalim on coronary arteries precontracted with 30 mmol/l KCl was competitively antagonized by 3 mumol/l glibenclamide, an ATP-sensitive potassium (KATP) channel blocker. In canine isolated epicardial large coronary arteries, 10 mumol/l JTV-506, 10 mumol/l levcromakalim, 100 mumol/l nicorandil and 0.1 mumol/l nifedipine eliminated 10 mmol/l 3,4-diaminopyridine-induced rhythmic contractions. In anesthetized dogs, when administered directly into the coronary artery, JTV-506 induced dose-dependent increases in coronary arterial diameter and coronary blood flow. These results suggest that JTV-506 elicits coronary vasorelaxation through activation of the KATP channel. It is expected that JTV-506 might be useful in the treatment of coronary vasospasm in angina pectoris. 相似文献
3.
Kazuhito Nomura Sonoko Sakawaki Eiji Sakawaki Ayumu Yamaoka Wakiko Aisaka Hiroyuki Okamoto Yoshihiro Takeyama Shuji Uemura Eichi Narimatsu 《Medicine》2021,100(19)
Introduction:Malignant catatonia (MC) is a movement disorder syndrome characterized by immobility, rigidity, and consciousness disorders that develops in association with mental and physical diseases. It is often fatal due to hyperthermia, rhabdomyolysis, and acute kidney injury. Its clinical symptoms are similar to those of another disorder, neuroleptic malignant syndrome (NMS), and it is often difficult to distinguish between the 2 disorders.Patient concerns:An Asian woman in her 60s with history of schizophrenia. She was admitted to our hospital because of symptoms such as fever, unconsciousness, and muscle rigidity. Blood tests showed kidney injury and high creatinine kinase levels.Diagnoses:At the time of admission, she had been diagnosed with NMS complicated by pulmonary aspergillosis and was undergoing treatment although there was no improvement.Interventions:Subsequently, the administration of propofol, a gamma-aminobutyric acid A agonist, markedly improved the symptoms, and the diagnosis was corrected to MC. At the beginning of her hospitalization, she received dantrolene, bromocriptine, amantadine, and L-3,4-dihydroxyphenylalanine as treatment for NMS, but her symptoms did not improve. With propofol, which is used for sedation, her catatonic symptoms improved markedly. Quetiapine administration further improved the symptoms, and it eventually resolved completely.Outcomes:The patient''s MC was in remission. Prolonged intensive care management resulted in a decline in activities of daily living, and she required rehabilitation at another hospital.Conclusion:This is the first report of MC with suspected involvement of pulmonary aspergillosis. MC differs from NMS, in that it is treated more effectively with gamma-aminobutyric acid A agonists. Although benzodiazepines are the first choice for the diagnosis and treatment of MC, they are ineffective for majority of patients with schizophrenia. However, even in such cases, propofol and quetiapine are effective, and they facilitate diagnosis and treatment. 相似文献
4.
It is well known that the luteal function in the patients with hyperprolactinemia is much suppressed by high level of serum prolactin. Present study was performed to investigate whether the luteal function in the patients with transient or occulted hyperprolactinemia was affected by the transient increase of serum prolactin level. The circadian changes of serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were examined in seven cases of the transient or occulted hyperprolactinemia whose BBT charts showed biphasic patterns. Serum prolactin levels of these patients were less than 25 ng/ml at daytime and more than 150 ng/ml at 30 minutes after the administration of 500 micrograms of TRH. Blood samplings were taken every two hours through an intravenous indwelling catheter without any disturbances. All of the patients had their breakfast at 7 to 8, lunch at 11 to 12 and dinner at 17 to 18 o'clock and slept from 22 until 6 in the next morning. Serum FSH, LH, prolactin, estrone, estradiol and progesterone levels were determined by RIA and the circadian changes of these hormones were analysed. Then, 5 mg of bromocriptine was administered every day to these patients for more than 30 days and the duration of the luteal phase and the mid-luteal serum estradiol and progesterone levels for the indicators of the luteal function were examined before and after the administration of bromocriptine. The circadian changes of serum prolactin levels in the patients showed significant increase during both daytime and night compared to those of the control (p less than 0.005, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
5.
Nahas SC Marques CF Araújo SA Aisaka AA Nahas CS Pinto RA Kiss DR 《Arquivos de gastroenterologia》2005,42(2):77-82
BACKGROUND: Since the sixties, when the optic fibers were reported, colonoscopy had emerged as the first line imaging investigation of the colon. AIM: To review the results of diagnostic and therapeutic colonoscopy at the Discipline of Coloproctology of the University of S?o Paulo Medical School, S?o Paulo, SP, Brazil, respecting the characteristics of an institution of medical education. METHODS: Retrospective analysis of basis related to 2,567 fibro colonoscopies between 1984 and 2002. The procedure was performed in hospitalized and in outpatients. The most common indications for colonoscopy were investigation of rectal bleeding and anemia (22.4%), change of bowel habit (14.76%), inflammatory bowel disease (8.65%) and carcinoma (7.25%). Bowel preparation with manitol was used by most of the patients. Sedation, when not contra-indicated, was administered. The most common combination was meperidine and benzodiazepine. All the exams were monitored with pulse oximeter. A normal colonoscopy to the point of maximum insertion was reported in 42.42% of procedures. The most common diagnosis was polyps (15.47%), followed by diverticular disease (12.86%). Inflammatory disease was recorded in 11.88% and carcinoma in 10.21%. Polypectomy was undertaken in 397 patients (2.21 polypectomy per patient with polyps). Colonoscopy was considered incomplete (when the colonoscope did not pass to the cecum or terminal ileum) in 181 (7.05%) cases. Perforation was reported in one patient who had a subestenosing retossigmoid tumor. In 0.42%, reasons for failing to complete the procedure included complication related to sedation, with no further prejudice for the patients. CONCLUSIONS: Colonoscopic examination of the entire colon remains the standard for visualization, biopsy and treatment of colonic affections. The incidence of complication of endoscopy of the large bowel is quite low, even in a school hospital. 相似文献
6.
Effects of sitting position on uterine activity during labor 总被引:1,自引:0,他引:1
To determine which components of uterine activity are affected by different positions of labor, 116 intrauterine pressure records in the sitting and supine positions were analyzed in order to measure resting, contraction, and bearing down pressures. The resting pressure in the sitting position showed consistent elevation compared to the supine position, while the contraction pressure did not differ strikingly in the two positions. The bearing down pressure in the sitting position for nulliparas during the second stage and for multiparas at the time of the 8- to 10-cm dilation was significantly higher than that in the supine position. Also, the sitting position led to a significantly shorter duration of the second stage in nulliparas and the 5- to 10-cm dilation period in multiparas. These findings suggest that the maternal position does not affect uterine contractility, that the increased resting pressure in the sitting position is of some importance in supplementing the downward delivery force, and that the increased bearing down pressure in the sitting position could help to significantly shorten the duration of labor. 相似文献
7.
Suzuki Y Kanada A Okaya Y Kurahashi Y Kogayu M Kobayashi T Aisaka K 《BJU international》2000,85(4):542-550
OBJECTIVE: To evaluate the effect of JTH-601-G1, an active metabolite and glucuronide conjugate of JTH-601 (an alpha1-adrenoceptor antagonist), on smooth muscle contraction in canine prostate and artery, and to examine the effect of JTH-601-G1 on prostatic urethral pressure and blood pressure in anaesthetized dogs. Materials and methods Male beagle dogs were used in both an in vitro and an in vivo study. In the former, the prostate and right common carotid artery were isolated, and smooth muscle strips from the prostate and open-ring strips from the carotid artery prepared. The effects of JTH-601-G1 on phenylephrine- and noradrenaline-induced contraction were assessed in these tissues. In the in vivo study, four dogs were anaesthetized and the change in urethral pressure, blood pressure and heart rate measured continuously. Vehicle (saline) and JTH-601-G1 were then infused intravenously in increasing doses (0.33-3.3 microg/kg/min for 30 min). In three other dogs, the effect of JTH-601-G1 infusion at a higher rate (25 microg/kg/min for 3 h) on blood pressure was evaluated, and the plasma concentration of JTH-601-G1 measured using high-performance liquid chromatography-mass spectrometry. RESULTS: Of the distinct metabolites of JTH-601, JTH-601-G1 had the most potent alpha1-adrenoceptor antagonistic effect in isolated canine prostate. JTH-601-G1 also antagonized alpha1-adrenoceptor agonist-induced contraction in common carotid artery, but the pA2 value in the artery was approximately 25 times higher than that in the prostate. In anaesthetized dogs, JTH-601-G1 decreased urethral pressure in a dose-dependent manner; at the highest dose, urethral pressure decreased by 24.5% and blood pressure by 7.0%. However, there was no significant change in heart rate at any dose. The plasma concentration of JTH-601-G1 increased with the dose of JTH-601-G1, but the concentration of both JTH-601 and other metabolites was below the detection limit. The higher JTH-601-G1 infusion rate caused blood pressure to decrease by only 6-10% even at JTH-601-G1 plasma concentrations of approximately 1500 ng/mL during the infusion. Although there was a negative correlation between mean blood pressure and plasma JTH-601-G1 concentration, the decrease in blood pressure was small compared with the reduction in urethral pressure. CONCLUSION: JTH-601-G1 appears to be a major active metabolite of JTH-601 but with a higher selectivity for canine prostate than artery. The results also indicate that in addition to the alpha1A-adrenoceptor, the alpha1L-adrenoceptor plays an important prostatic selective role in smooth muscle contraction via the alpha1-adrenoceptor. 相似文献
8.
Second Primary Cancers Following Non-Hodgkin's Lymphoma in Japan: Increased Risk of Hepatocellular Carcinoma 总被引:1,自引:0,他引:1
Hideo Tanaka Hideaki Tsukuma Hirofumi Teshima Wakiko Ajiki Yohko Koyama Noriko Kinoshita Tohru Masaoka Akira Oshima 《Cancer science》1997,88(6):537-542
We evaluated the risk of development of second primary cancers, with particular reference to subsequent hepatocellular carcinoma (HCC), in 592 patients diagnosed as non-Hodgkin's lymphoma (NHL), at Osaka Medical Center for Cancer and Cardiovascular Diseases. During 1978–1994, 2,163 person-years of observation were accrued, and 27 of the patients developed a second primary cancer, yielding an observed-to-expected ratio (O/E) of 1.53 [95% confidence interval (CI) = 1.01–2.23]. Significant excess risk was noted for primary liver cancer (PLC; O/E=4.36, 95% CI=1.99–8.28; O =9) and non-lymphocytic leukemia (O/E=26.17, 95% CI=5.26–76.46; O=3). The excess risk of PLC was relatively constant within the first 10 years after the NHL diagnosis. Patients who received chemotherapy as the NHL treatment had a significantly increased risk of PLC (O/E=5.91, 95% CI =2.70–11.23; O=9). Their clinical reports indicated that all nine patients with PLC were diagnosed as HCC, and eight of them had clinical and/or histologic evidence of cirrhosis at the time of HCC diagnosis. None of the nine patients had a history of blood transfusion between the first NHL treatment and the diagnosis of HCC. These findings suggested that Japanese NHL patients might have an increased risk of developing HCC, and they indicated the importance of medical surveillance for liver malignancies, as well as subsequent leukemias. Possible explanations for the excess risk of subsequent HCC are discussed. 相似文献
9.
Cancer mortality is generally high in people of low socioeconomic status compared with people of high socioeconomic status (SES). Although these differences in mortality may be caused by differences in cancer incidence and survival, analysis of these factors has rarely been conducted. The objective of our cross-sectional ecological study was to analyze socioeconomic differences in cancer incidence, mortality and survival in a metropolitan area of Japan. The age-adjusted cancer incidence rates, age-adjusted mortality rates, relative 5-year survival, and proportions of early stage cancer were calculated for 67 municipalities in Osaka, Japan. For area-based socioeconomic variables, we used the percentages of male unemployment, college or graduate school graduates, home ownership, households receiving government assistance, and households below the subsistence habitation level in each municipality. We performed linear regression taking each municipality's population as weight to examine the relationships between measurements relating cancer and socioeconomic variables. Factor analysis of socioeconomic variables was carried out to determine whether a particular socioeconomic variable tended to be associated with another. Cancer incidence, cancer mortality, 5-year cancer survival, and proportion of early stage cancer were highly correlated with each socioeconomic variable at the municipality level. Five area-based socioeconomic variables could be explained by three factors: economic status, housing characteristics and educational attainment. Despite the major limitation of a lack of individual information about socioeconomic characteristics and outcomes related to cancer, we hypothesize that a municipal area's socioeconomic status might be a predictor of individual incidence, mortality, and survival of cancer. 相似文献
10.
T Ohkura S Yamada A Tohma R Kimura K Aisaka 《Biological & pharmaceutical bulletin》1999,22(7):687-690
In vitro, ex vivo and in vivo alpha1-adrenoceptor binding of JTH-601 (3-[N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethyl]-N-methylaminometh yl]-4-methoxy-2,5,6-trimethyl-phenol hemifumarate), a novel alpha1L-adrenoceptor antagonist, in rat tissues was investigated. JTH-601 competed in a concentration-dependent manner with [3H]prazosin for binding sites in the prostate, submaxillary gland and spleen of rats in vitro, and the inhibitory effect was not largely different among these tissues, as shown by the Ki values of 2-3 nM. At 0.25, 0.5 and 3 h after oral administration of JTH-601 (6.5 micromol/kg) in rats, there was a significant (57, 64 and 28%, respectively) increase in the apparent dissociation constant (Kd) for prostatic [3H]prazosin binding, compared to the control value. The administration of a higher dose (21.8 micromol/kg) of this agent produced greater (67-99%) increases in Kd values for prostatic [3H]prazosin binding at 0.5-12 h later. Similar significant increases in Kd values, as with the prostate, were seen in the submaxillary gland and heart 0.25-12 h after the oral administration of JTH-601 (6.5 and 21.8 micromol/kg), but significant increases in the spleen and cerebral cortex were seen only at 0.25-3 h and 0.5 h, respectively. At 10 min of i.v. injection of [3H]JTH-601 in rats, in vivo specific binding was observed in the prostate, cerebral cortex, submaxillary gland, spleen and heart but not in the aorta. The binding in the prostate, submaxillary gland and heart, but not in the cerebral cortex and spleen, lasted until 120 min. It is concluded that JTH-601 may exert a considerably sustained blockade of alpha1-adrenoceptors in the prostate of rats. This finding may be important in characterizing the therapeutic effect of JTH-601 for bladder outlet obstruction in patients with benign prostatic hyperplasia. 相似文献