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11.
12.
A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles. 总被引:2,自引:0,他引:2
Alf Lamprecht Hiromitsu Yamamoto Hirofumi Takeuchi Yoshiaki Kawashima 《Journal of controlled release》2005,104(2):337-346
Nanoparticles (NP) are known to accumulate at the site of inflammation in inflammatory bowel disease. In order to avoid premature uptake or degradation of NP during their passage through the small intestine, it appeared necessary to devise a form of local delivery system for NP. Tacrolimus (FK506) loaded poly(lactic-co-glycolic acid) NP entrapped into pH-sensitive microspheres (NPMS) were designed to achieve greater selectivity to their site of action when administered orally. The therapeutic efficacy of this drug delivery system was tested in an experimental colitis in rats. The in vitro characterization showed a successful incorporation of FK506-NP and strongly pH-sensitive release kinetics of both NP and drug. During the in vivo studies, clinical activity, colon/body weight index, and myeloperoxidase activity were determined to assess the severity of inflammation. Systemic availability of a fluorescent dye entrapped in the microspheres was measured in order to determine possible adverse effects. The NPMS as well as the controls of NP and MS formulations exhibited significant mitigating effects in the clinical activity index after 3 days of treatment with similar levels for the various therapies. When observing colon/body weight index and myeloperoxidase activity, only the NPMS group reached statistically significant differences (P<0.05) compared to the colitis control group while other groups did not (colitis control: 21.94+/-4.97; FK506 solution: 15.81+/-3.42; FK506-NP: 17.03+/-5.52; FK506-MS: 15.17+/-7.81; and FK-NPMS: 10.26+/-7.76 U/mg tissue). Moreover, the NPMS system reduced the systemic absorption of the entrapped dye compared to the dye solution or simple NP formulation (relative biovailability-solution: 100+/-14.9%; NP: 46.8+/-8.6%; and NPMS: 29.4+/-3.3%). The results suggest that the NPMS system can provide selective delivery of NP in the colon and develop a significant mitigating effect, while the control group treatments appeared to be insufficient. 相似文献
13.
Y Moriyama Y Morishita H Toyohira S Shimokawa Y Umebayashi H Saigengi S Kawashima A Taira 《Kyobu geka. The Japanese journal of thoracic surgery》1990,43(7):538-542
Four patients with descending thoracic aortic aneurysm were successfully operated on under temporary bypass with an antithrombogenic tube and a Bio-Medicus centrifugal pump. The bypass flow ranged from 1.0 to 2.4 l/min with the mean femoral artery pressure of 50 to 70 mmHg. No complications such as paraplegia, hepatic dysfunction or renal failure were encountered in all the patients. Temporary increment of the serum amylase level occurred in all the patients, but any apparent clinical symptoms were not present. The temporary bypass method with an antithrombogenic tube and a centrifugal pump is useful and reliable for surgical treatment of descending thoracic aortic aneurysm. 相似文献
14.
Tetsumori Yamashima Takaomi C. Saido Masatoshi Takita Atsuo Miyazawa Jun Yamano Atsuo Miyakawa Hisashi Nishijyo Junkoh Yamashita Seiichi Kawashima Taketoshi Ono Tohru Yoshioka 《The European journal of neuroscience》1996,8(9):1932-1944
To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP2) and Ca2+ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP2. Activated μ-calpain and PIP2 were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca2+ mobilization with increased PIP2 immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca2+ and PIP2 breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death. 相似文献
15.
Goichi Yotsumoto Koki Tanaka Naoki Ishizaki Akira Ikoma Sumihiro Kawashima Akira Taira 《Surgery today》1997,27(7):657-660
We report herein a case of spontaneous subcapsular hepatic hemorrhage which occurred in a 33-year-old woman 1 day after she
had been delivered of her second child by cesarean section following an uneventful pregnancy. She complained of right upper
quadrant pain on the 1st postoperative day, and computed tomography (CT) showed subcapsular low-density masses in both liver
lobes, while extravasation was demonstrated by CO2 intraarterial digital subtraction angiography (IADSA). The hemorrhage was successfully controlled by transcatheter arterial
embolization (TAE). However, on the 3rd day after TAE, an exploratory laparotomy was performed to establish an exact diagnosis
to explain the persistent abdominal pain and abnormal liver function tests. Subcapsular hematomas in both lobes were confirmed
and no visible laceration was present. The patient recovered gradually by spontaneous absorption of the hematomas and was
discharged on the 22nd postoperative day. Spontaneous hepatic hemorrhage associated with pregnancy is a very rare complication,
and establishing a correct diagnosis and initiating appropriate therapy are essential for this life-threatening disease. 相似文献
16.
T Ohashi F Yamamoto H Yamamoto H Ichikawa T Shibata Y Shimada T Ishikawa K Kagisaki Y Kumada Y Kawashima 《[Zasshi] [Journal]. Nihon Kyōbu Geka Gakkai》1992,40(11):1998-2004
The effects of potassium in reperfusion solution (RS) and the influence of sodium on this effect were studied. Experimental time course was as followed: 20 min working perfusion, 3 min cardioplegic infusion with St. Thomas Cardioplegic Solution followed by global ischemia for 33 or 35 min at 37.5 degrees C, 15 min early Langendorff reperfusion with several different potassium concentration modified with Krebs Henseleit Bicarbonate Buffer (KHBB) containing 145 mM and 110 mM sodium and 5 min late reperfusion with KHBB, followed by 20 min working perfusion. Potassium in RS possessed bell shaped dose response nature with optimal concentration of 10 mM in the condition of 145 mM sodium but 6 m in the condition of 110 mM in terms of percent recovery of aortic flow. Although higher potassium reperfusion produced less Creatine Kinase leakage. 相似文献
17.
László Prónai Hiroe Nakazawa Kohji Ichimori Yoshinori Saigusa Tomoichi Ohkubo Kazuko Hiramatsu Shigeru Arimori János Fehér 《Inflammation》1992,16(5):437-450
This study was performed to examine the pattern of Superoxide (O
2
–
·) generation from leukocytes using the O
2
–
· specific chemiluminescence (CL) method.Cypridina luciferin analog, 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA) was used as a CL probe. The appropriate conditions of the MCLA method was first determined for the evaluation of the time course of O
2
–
· generation by leukocytes. The time course of O
2
–
· generation obtained by the MCLA-CL system was compared with that by the luminol-dependent CL, electron spin resonance (ESR)/spin trapping, and cytochromec systems. Following stimulation by three different stimulants (PMA, OZ, FMLP), leukocytes continuously generated O
2
–
· for up to 5 h in the MCLA-CL system, irrespective of the kind of stimulation. The curves obtained by generation ceased more rapidly in the luminol-CL, ESR/spin trapping, and cytochromec systems. A 50% activity of the initial value was observed at 70 min in the MCLA-CL system, but 30, 10 and 35 min in the other systems, respectively. The CL or O
2
–
· generation value decreased to less than 1% (possible termination) at 300, 90, 120 and 180 min, respectively. With the exception of ESR studies with OZ, the cell viability was not significantly affected in any of the trials. These results indicate that leukocytes can generate O
2
–
· much longer than previously estimated and that the MCLA-CL-system is the most suitable system for the measurement of the O
2
–
· generation by leukocytes. 相似文献
18.
19.
M Nakaya K Kawazoe K Ohara Y Kosakai Y Kito Y Kawashima 《[Zasshi] [Journal]. Nihon Kyōbu Geka Gakkai》1992,40(9):1764-1766
The authors reported the first case of acute spinal epidural hematoma (SEH) developed after open heart surgery. The patient was noticed that her legs felt weak and numb on the first postoperative day evening. On the next day morning, neurological examination revealed that flaccid paralysis of both legs and also loss of all sensory perception below the level of Th-6 spine bilaterally. The prolonged effect of anesthesia and painless onset made delayed recognition of the lesion. SEH (Th5-7) was diagnosed with MRI and decompressive surgery was immediately done, sixty hours after the beginning of cardiac operation. But in this case neurological deficits were not changed. We concluded that a routine diagnostic approach was very important procedure to find out this serious complication for all patients underwent open heart surgery in early period of its onset. 相似文献
20.
Koibuchi Yukio; Iino Yuichi; Joshita Takashi; Yokoe Takao; Shinkai Hiroko; Kawashima Kenji; Kobayash Junya; Tanaka Sunao; Oyama Tetsunari; Hikino Toshiaki; Morishita Yasuo 《Japanese journal of clinical oncology》1995,25(6):273-277
A 66-year-old woman time of 10 days. One month after radicalmastectomy, there was local recurrence, followed by multiplepulmonary metastases, and the patient died of respiratory failure5 months after surgery. The gray-white-colored tumor measured13x12x;10 cm, and its border was well defined. The tumor wascomposed of diffusely growing round or polygonal cells withvesicular nuclei, prominent nucleoli, and ample cytoplasm containingeosinophilic inclusions. Lymph node involvement was widespread.Both vimentin and keratin were clearly demonstrated by immunohistochemicalstaining. Ultrastructural studies revealed that the MRT cellscontained cytoplasmic whorls of intermediate filaments. 相似文献