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51.
Type V phosphodiesterase expression in cerebral arteries with vasospasm after subarachnoid hemorrhage in a canine model 总被引:4,自引:0,他引:4
Cyclic GMP (cGMP) mediates smooth muscle relaxation in the central nervous system. In subarachnoid hemorrhage (SAH), decreases in intrinsic nitric oxide (NO) cause cerebral vasospasms due to the regulation of cGMP formation by NO-mediated pathways. As phosphodiesterase type V (PDE V) selectively hydrolyzes cGMP, we hypothesized that PDE V may function in the initiation of vasospasm. This study sought to identify the altered PDE V expression and activity in the vasospastic artery in a canine SAH model. We also used this system to examine possible therapeutic strategies to prevent vasospasm. Using a canine model of SAH, we induced cerebral vasospasm in the basilar artery (BA). Following angiographic confirmation of vasospasm on day 7, PDE V expression was immunohistochemically identified in smooth muscle cells of the vasospastic BA but not in cells of a control artery. The isolation of PDE enzymes using a sepharose column confirmed increased PDE V activity in the vasospastic artery only through both inhibition studies, using the highly selective PDE V inhibitor, sildenafil citrate, and Western blotting. Preliminary in vivo experiment using an oral PDE V inhibitor at 0.83 mg kg(-1) demonstrated partial relaxation of the spastic BA. PDE V activity was increased from control levels within the BA seven days after SAH. PDE V expression was most prominent in smooth muscle cells following SAH. These results suggest that clinical administration of a PDE V inhibitor may be a useful therapeutic tool in the prevention of vasospasm following SAH. 相似文献
52.
Ken-ichi Nibu M.D. Ken Nakagawa M.D. Shin-etsu Kamata M.D. Kazuyoshi Kawabata M.D. Munenaga Nakamizo M.D. Tomohiko Nigauri M.D. Katufumi Hoki M.D. 《American journal of otolaryngology》1997,18(6):391
Purpose: As locoregional control of head and neck cancer has improved, distant metastases have become increasingly common problems.Patients and Methods: To determine the role of surgical treatment, we reviewed 32 patients with squamous cell carcinoma (SCC) of the head and neck who underwent thoracotomy for pulmonary metastases.Results: The overall 5-year survival rate was 32%. The 5-year survival rate of the patients with SCC of the oral cavity was significantly poorer than that of the patients with other primary site (15.4% v 45.2%; P = .01). In the patients with single nodule, extent of the tumor was a significant prognostic factor (P = .007). Mediastinal lymph node involvement (P = .004) and pleural invasion (P = .04) also correlated with survival.Conclusion: TNM classification of the primary tumor did not have an impact on survival in this study. Further studies of a large series should be performed to determine the indications and modalities of the surgical treatment for pulmonary metastases of the SCC of head and neck. 相似文献
53.
Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons 总被引:4,自引:0,他引:4
Kanki R Nakamizo T Yamashita H Kihara T Sawada H Uemura K Kawamata J Shibasaki H Akaike A Shimohama S 《Brain research》2004,1015(1-2):73-81
Glutamate-induced excitotoxicity is implicated as playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), and mitochondrial dysfunction is also found in ALS patients. We investigated the relationship between glutamate excitotoxicity and mitochondrial dysfunction elicited by rotenone (a complex I inhibitor), malonate (a complex II inhibitor), or antimycin (a complex III inhibitor), in primary cultures of the embryonic rat spinal cord. Rotenone and malonate induced relatively selective toxicity against motor neurons as compared to non-motor neurons, whereas antimycin caused non-selective toxicity. The toxicity of rotenone was prevented by a non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not by an NMDA receptor antagonist, 5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). The toxicity of malonate was blocked by both CNQX and MK-801. The toxicity of antimycin was affected by neither CNQX nor MK-801. When mitochondrial complex I was mildly inhibited by a sub-lethal concentration of rotenone, AMPA-induced motor neuron death was significantly exacerbated. A sub-lethal concentration of malonate exacerbated both NMDA- and AMPA-induced motor neuron death. These data suggest that mitochondrial dysfunction predisposes motor neurons to ionotropic glutamate receptor-mediated excitotoxicity. 相似文献
54.
We describe an extremely rare case of subcapsular rupture of the liver associated with hemophilia A in a neonate. Although, the neonate was in good condition after birth, at 13 hours, he became pale and his abdomen distended. At 17 hours after birth, an emergency laparotomy was performed. The subcapsular rupture of the left side of the liver was found. The ruptured area was closed with a continuous suture, and additional mattress sutures with pledget provided satisfactory hemostasis. On the second day after the operation, relaparotomy was done because recurrent bleeding was suspected. There was no bleeding from the sutured liver. Oozing was found at the suture line on the abdominal wall. An additional postoperative observation was a decrease of factor VIII less than 1%, and hemophilia A was confirmed. 相似文献
55.
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57.
A comparison of the endocrine effects of hypotension induced by nicardipine with those by sodium nitroprusside in dogs 总被引:2,自引:0,他引:2
S Takeda Y Inada N Nakamizo N Nomura T Tomaru H Negishi A Hosoyamada 《Masui. The Japanese journal of anesthesiology》1991,40(7):1063-1069
Plasma catecholamines, plasma renin activity, plasma aldosterone and plasma cortisol during hypotension induced by sodium nitroprusside and nicardipine were studied in 27 mongrel dogs under 0.87% halothane in oxygen. They were randomly divided into three groups: sodium nitroprusside (group S: n = 8), nicardipine (group N: n = 8) and controls (group C: n = 9). Group C received no vasodilator therapy and served as a control. Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes in hypotensive groups. No changes were noted in plasma catecholamines and plasma cortisol in group C throughout the experiment, but plasma renin activity and plasma aldosterone decreased progressively. During hypotension induced by sodium nitroprusside and nicardipine, plasma epinephrine was significantly higher than the control value. However, after the hypotensive drugs were discontinued, plasma epinephrine decreased slightly. During and after induced hypotension, plasma renin activity of group N and group S were significantly higher than the control values. The highest levels of plasma renin activity 36.7 ng.ml-1.hr-1 in group N and 23.2 ng.ml-1.hr-1 in group S were observed. Plasma aldosterone concentration was significantly higher than the control value in group N. The maximum increase occurred 30 minutes after discontinuation of the nicardipine and the highest concentration of plasma aldosterone was three times control value. In contrast, in group S, plasma aldosterone was unchanged from the control value. Plasma cortisol concentration of group N was significantly increased than the control value. However, in group S, plasma cortisol concentration showed a slight but not significant increase.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
58.
K Ohmori H Ishii T Hirayama K Shuto N Nakamizo 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1982,80(3):251-260
The present experiment was an attempt to clarify the pharmacological properties of oxatomide. Oxatomide administered i.v. was found to be as active as disodium cromoglycate (DSCG) in inhibiting the IgE-mediated 48 hr homologous PCA in rats. In contrast to DSCG, oxatomide was also effective when administered p.o. Oxatomide inhibited the IgG-mediated 4 hr heterologous PCA in guinea pigs. However, DSCG did not prevent this reaction. In an attempt to determine at what stage in the PCA reaction oxatomide was effective, the experiment was performed utilizing a double sensitization technique with two different IgE antibodies, anti-dinitrophenylated-ascaris extract and anti-egg albumin. When the same antigen was challenged twice in sequence, the second antigen challenge did not produce the PCA regardless of the presence or absence of oxatomide at the initial antigen challenge. However, the presence of oxatomide during the period of the first challenge preserved completely the PCA responsiveness of the tissue to the second challenge with the other antigen. Similar results were obtained with DSCG. These results suggest that oxatomide may not impair the antigen-antibody combination, but it probably prevents the release of chemical mediators in a manner similar to DSCG. 相似文献
59.
4-(2-Hydroxy-3-[(1-methyl-3-phenylpropyl)amino] propoxy)benzeneacetamide (KF-4317) differs from conventional adrenoceptor antagonists in producing a competitive blockade at both alpha- and beta 1-adrenoceptors. In blocking beta 1-adrenoceptors, KF-4317 is as active as labetalol in both in vitro and in vivo experiments, and 22 times less potent (in vitro) and 2 times less potent (in vivo) than propranolol. In blocking beta 2-adrenoceptors, KF-4317 is 776 times less potent (in vitro) and 83 times less potent (in vivo) than propranolol. The ratio of beta 1-blocking activity to beta 2-blocking activity is 33 to 145 for practolol, 37 for KF-4317, 1 for propranolol and 0.16 to 1 for labetalol, respectively. In blocking alpha-adrenoceptors, KF-4317 is 55 times less potent than phentolamine and 6 times less potent than labetalol in in vitro experiments, but as active as labetalol in in vivo experiments. These results show that KF-4317 possesses a novel type of adrenoceptor antagonistic property. 相似文献