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11.
Michael H. Rivner Thomas R. Swift Barbara O. Crout W. Trojaborg A. Moon B. B. Andersen N. S. Trojaborg P. Liam Oey Joe V. Trontelj Erik Stlberg Joe V. Trontelj Betty Soliven Ricardo Maselli Suat Topaktas Sefik Dener Meliha Kenis Turgay Dalkara Kieko Genba Yoshikazu Ugawa Ichiro Kanazawa Ichiro Okutsu Ikki Hamanaka Toshihiko Yoshida Masato Morita Youko Yamanouchi Koichi Okamoto Shunsaku Hirai William Camu Michel Billiard 《Muscle & nerve》1993,16(5):562-570
12.
Anlar Şule Çapan Yilmaz Güven Olgun Göğüş Ahmet Dalkara Turgay Hincal Atillâ 《Pharmaceutical research》1994,11(2):231-236
Buccoadhesive controlled-release systems for the delivery of morphine sulfate were prepared by compression of hydroxypropyl methylcellulose (HPMC) with carbomer (CP), which served as the bioactive adhesive compound. The release behavior of systems containing 30 mg of morphine sulfate and various amounts of the two polymers was found to be non-Fickian. The adhesion force was significantly affected by the mixing ratio of HPMC and CP in the tablet, and the weakest adhesion force was observed at a ratio of 1:1 (HPMC:CP). Interpolymer complex formation was confirmed between HPMC and CP in acidic medium by turbidity, viscosity, and FT-IR measurements. The amount absorbed (percentage of the drug loaded) of the controlled-release buccoadhesive tablets in six healthy volunteers and was 30 ± 5%. 相似文献
13.
VEGF protects brain against focal ischemia without increasing blood--brain permeability when administered intracerebroventricularly. 总被引:5,自引:0,他引:5
Dilaver Kaya Yasemin Gürsoy-Ozdemir Muge Yemisci Ne?e Tuncer Sevin? Aktan Turgay Dalkara 《Journal of cerebral blood flow and metabolism》2005,25(9):1111-1118
Delayed administration of vascular endothelial growth factor (VEGF) promotes functional recovery after focal cerebral ischemia. However, early intravenous injection of VEGF increases blood-brain barrier (BBB) leakage, hemorrhagic transformation and infarct volume whereas its application to cortical surface is neuroprotective. We have investigated whether or not early intracerebroventricular administration of VEGF could replicate the neuroprotective effect observed with topical application and the mechanism of action of this protection. Mice were subjected to 90 mins middle cerebral artery (MCA) occlusion and 24 h of reperfusion. Vascular endothelial growth factor (8 ng, intracerebroventricular) was administered 1 or 3 h after reperfusion. Compared with the vehicle-treated (intracerebroventricular) group, VEGF decreased the infarct volume along with BBB leakage in both treatment groups. Neurologic disability scores improved in parallel to the changes in infarct volume. Independently of the decrease in infarct size, VEGF also reduced the number of TUNEL-positive apoptotic neurons. Phospo-Akt levels were significantly higher in ischemic hemispheres of the VEGF-treated mice. Contrary to intracerebroventricular route, intravenous administration of VEGF (15 microg/kg) enhanced the infarct volume as previously reported for the rat. In conclusion, single intracerebroventricular injection of VEGF protects brain against ischemia without adversely affecting BBB permeability, and has a relatively long therapeutic time window. This early neuroprotective action, observed well before recovery-promoting actions such as angiogenesis, possibly involves activation of the PI-3-Akt pathway. 相似文献
14.
Cerebrovascular alterations in mice lacking neuronal nitric oxide synthase gene expression. 总被引:6,自引:0,他引:6 下载免费PDF全文
K Irikura P L Huang J Ma W S Lee T Dalkara M C Fishman T M Dawson S H Snyder M A Moskowitz 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(15):6823-6827
Nitric oxide (NO) is known to mediate increases in regional cerebral blood flow elicited by CO2 inhalation. In mice with deletion of the gene for neuronal NO synthase (NOS), CO2 inhalation augments cerebral blood flow to the same extent as in wild-type mice. However, unlike wild-type mice, the increased flow in mutants is not blocked by the NOS inhibition, N omega-nitro-L-arginine, and CO2 exposure fails to increase brain levels of cGMP. Topical acetylcholine elicits vasodilation in the mutants which is blocked by N omega-nitro-L-arginine, indicating normal functioning of endothelial NOS. Moreover, immunohistochemical staining for endothelial NOS is normal in the mutants. Thus, following loss of neuronal NOS, the cerebral circulatory response is maintained by a compensatory system not involving NO. 相似文献
15.
The imidazole ring in nafimidone [1-(2-naphthyl)-2-(1-imidazolyl)ethanone] was substituted with various groups to investigate the significance of the imidazole ring in anticonvulsant activity. For this purpose, some 2-acetylnaphthalene derivatives and their reduction products were synthesized. Several N-alkylation methods were used to prepare 2-acetylnaphthalenes. NaBH4 was used to synthesize their reduction products. Anticonvulsant activities of these compounds were determined by phase I tests of Antiepileptic Drug Development Programme. 相似文献
16.
The objective of our study was to prepare and characterize basic fibroblast growth factor (bFGF)-loaded nanoparticles. Protein-loaded chitosan nanoparticles were obtained by ionotropic gelation process based on the interaction between chitosan and tripolyphosphate (TPP). The protein-loading capacity and encapsulation efficiency were 0.021% and 27.388%, respectively. The bFGF-loaded nanoparticles have a mean diameter of 424 nm, a narrow size distribution, spherical shape and positive surface charges. In vitro release showed that the extent of release was 68% at 24 hr. The protein integrity was investigated by SDS-PAGE analysis that confirmed protein integrity was not affected by the encapsulation procedure and release conditions. 相似文献
17.
Didem Dayangac-Erden Gamze Bora-Tatar Sevim Dalkara Ayhan S. Demir Hayat Erdem-Yurter 《Archives of Medical Science》2011,7(2):230-234
Introduction
Proximal spinal muscular atrophy (SMA) is a common autosomal recessively inherited neuromuscular disorder. It is caused by homozygous absence of the survival motor neuron 1 (SMN1) gene. SMN2, which modulates the severity of the disease, represents a major target for therapy. The aim of this study was to investigate whether SMN2 expression can be increased by caffeic acid, chlorogenic acid and curcumin, which are designed by modifications of the carboxylic acid class of histone deacetylase (HDAC) inhibitors.Material and methods
Using quantitative real-time PCR, we analysed the levels of full-length SMN2 and Δ7SMN2 mRNA. We performed LDH cytotoxicity assay to analyse whether SMN2 activating concentrations of caffeic acid, chlorogenic acid and curcumin were cytotoxic to fibroblasts.Results
We found that caffeic acid and curcumin were more efficient than chlorogenic acid and increased full-length SMN2 mRNA levels 1.5 and 1.7-fold, respectively. Δ7SMN2 mRNA levels were measured to investigate alternative splicing of exon 7. We also found that cytotoxicity was not observed at SMN2 activating concentrations.Conclusions
Our data suggest that carboxylic acid derivatives including phenolic structure and symmetry could be a good candidate for SMA treatment. 相似文献18.
Pericytes are located at periphery of the microvessel wall and wrap it with their processes. They communicate with other cells
of the neurovascular unit by direct contact or through signaling pathways and regulate several important microcirculatory
functions. These include development and maintenance of the blood–brain barrier (BBB), distribution of the capillary blood
flow to match the local metabolic need of the nearby cells, and angiogenesis. Pericytes also exhibit phagocytic activity and
may function as pluripotent stem cells. Increasing evidence suggests a role for pericytes in a wide range of CNS diseases.
They appear to be vulnerable to oxygen and nitrogen radical toxicity and have been shown to contract during cerebral ischemia
and remain contracted despite reopening of the occluded artery. This causes impaired re-flow and may diminish the benefit
of re-canalization therapies in stroke patients. Hyperglycemia-induced dysfunction of the signaling pathways between pericytes
and endothelia is thought to play an important role in diabetic retinopathy, a common cause of blindness. Amyloid deposits
detected within degenerating pericytes in the brains of patients with Alzheimer’s disease suggest that pericyte dysfunction
may play a role in cerebral hypoperfusion and impaired amyloid β-peptide clearance in Alzheimer’s disease. This exciting possibility
may reveal a novel temporal sequence of events in chronic neurodegeneration, in which microvascular dysfunction due to pericyte
degeneration initiates secondary neurodegenerative changes. Identification of molecular mechanisms by which pericytes regulate
BBB integrity in inflammatory conditions as well as in vasogenic brain edema may lead to new treatments. Pericytes may also
take part in tissue repair and vascularization after CNS injury. In conclusion, although the evidence is just emerging and
mostly preliminary, disclosing pericytes’ role in the pathophysiology of CNS diseases may yield exciting developments and
novel treatments. 相似文献
19.
Turgay Dalkara Ethem Murat Arsava 《Journal of cerebral blood flow and metabolism》2012,32(12):2091-2099
Substantial experimental data and recent clinical evidence suggesting that tissue reperfusion is a better predictor of outcome after thrombolysis than recanalization necessitate that patency of microcirculation after recanalization should be reevaluated. If indeed microcirculatory blood flow cannot be sufficiently reinstituted despite complete recanalization as commonly observed in coronary circulation, it may be one of the factors contributing to low efficacy of thrombolysis in stroke. Although microvascular no-reflow is considered an irreversible process that prevents tissue recovery from injury, emerging evidence suggests that it might be reversed with pharmacological agents administered early during recanalization. Therefore, therapeutic approaches aiming at reducing microvascular obstructions may improve success rate of recanalization therapies. Importantly, promoting oxygen delivery to the tissue, where entrapped erythrocytes cannot circulate in capillaries, with ongoing serum flow may improve survival of the underreperfused tissue. Altogether, these developments bring about the exciting possibility that benefit of reperfusion therapies can be further improved by restoring microcirculatory function because survival in the penumbra critically depends on adequate blood supply. Here, we review the available evidence suggesting presence of an ‘incomplete microcirculatory reperfusion'' (IMR) after focal cerebral ischemia and discuss potential means that may help investigate IMR in stroke patients after recanalization therapies despite technical limitations. 相似文献
20.
Didem Dayangaç‐Erden Gamze Bora Peruze Ayhan Çetin Kocaefe Sevim Dalkara Kemal Yelekçi Ayhan S. Demir Hayat Erdem‐Yurter 《Chemical biology & drug design》2009,73(3):355-364
Spinal muscular atrophy is an autosomal recessive motor neuron disease that is caused by mutation of the survival motor neuron gene (SMN1) but all patients retain a nearly identical copy, SMN2. The disease severity correlates inversely with increased SMN2 copy. Currently, the most promising therapeutic strategy for spinal muscular atrophy is induction of SMN2 gene expression by histone deacetylase inhibitors. Polyphenols are known for protection against oxidative stress and degenerative diseases. Among our candidate prodrug library, we found that (E )‐resveratrol, which is one of the polyphenolic compounds, inhibited histone deacetylase activity in a concentration‐dependent manner and half‐maximum inhibition was observed at 650 μm . Molecular docking studies showed that (E )‐resveratrol had more favorable free energy of binding (?9.09 kcal/mol) and inhibition constant values (0.219 μm ) than known inhibitors. To evaluate the effect of (E )‐resveratrol on SMN2 expression, spinal muscular atrophy type I fibroblast cell lines was treated with (E )‐resveratrol. The level of full‐length SMN2 mRNA and protein showed 1.2‐ to 1.3‐fold increase after treatment with 100 μm (E )‐resveratrol in only one cell line. These results indicate that response to (E )‐resveratrol treatment is variable among cell lines. This data demonstrate a novel activity of (E )‐resveratrol and that it could be a promising candidate for the treatment of spinal muscular atrophy. 相似文献