Home About us Contact
|
Home About us Contact | ||
|
|
||
Ischemic Condition (ischemic + condition)
Selected AbstractsLipid-Like Nanoparticles for Small Interfering RNA Delivery to Endothelial CellsADVANCED FUNCTIONAL MATERIALS, Issue 19 2009Seung-Woo Cho Abstract Here, nanoparticles composed of lipid-like materials (lipidoids) to facilitate non-viral delivery of small interfering RNA (siRNA) to endothelial cells (ECs) are developed. Nanoparticles composed of siRNA and lipidoids with small size (,200,nm) and positive charge (,34,mV) are formed by self-assembly of lipidoids and siRNA. Ten lipidoids are synthesized and screened for their ability to facilitate the delivery of siRNA into ECs. Particles composed of leading lipidoids show significantly better delivery to ECs than a leading commercially available transfection reagent, Lipofectamine 2000. As a model of potential therapeutic application, nanoparticles composed of the top performing lipidoid, NA114, are studied for their ability to deliver siRNA targeting anti-angiogenic factor (SHP-1) to human ECs. Silencing of SHP-1 expression significantly enhances EC proliferation and decreases EC apoptosis under a simulated ischemic condition. [source] Enhanced Connexin 43 immunoreactivity in penumbral areas in the human brain following ischemiaGLIA, Issue 5 2006Taizen Nakase Abstract Astrocytes support neurons not only physically but also chemically by secreting neurotrophic factors and energy substrates. Moreover, astrocytes establish a glial network and communicate through gap junctions in the brain. Connexin 43 (Cx43) is one of major component proteins in astrocytic gap junctions. Heterozygote Cx43 KO mice and astrocyte specific Cx43 KO mice exhibited amplified brain damage after ischemic insults, suggesting a neuroprotective role for astrocytic gap junctions. However, some reports mentioned unfavorable effects of gap junctions in neuronal support. Therefore, the role of astrocytic gap junctions under ischemic condition remains controversial. Since these studies have been performed using animal models, we investigated the Cx43 expression in human brain after stroke. Brain slice sections were prepared from pathological samples in our hospital. Embolic stroke brains sectioned because of the stroke were considered as acute ischemic models. Multiple infarction brains sectioned because of pneumonia or cancer were considered as chronic models. We observed the levels of Cx43 in both lesioned and intact areas, and compared them with acute and chronic models. As the results, astrocytes were strongly activated in penumbral lesions both of acute and chronic ischemic models. The Cx43 immunoreactivity was significantly amplified in the penumbra of chronic model compared to that of the acute model. Neurons were well preserved in chronic model compared to acute model. These findings suggested that the brain may generate neuronal protection by increasing the levels of Cx43 and amplifying the astrocytic gap junctional intercellular communication under hypoxic condition. © 2006 Wiley-Liss, Inc. [source] Retention, Distribution, and Effects of Intraosseously Administered Ibandronate in the Infarcted Femoral Head,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007James Aya-ay Abstract The local distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted femoral heads were studied. Intraosseous administration effectively delivered and distributed ibandronate in the infarcted femoral heads and decreased the femoral head deformity in a large animal model of Legg-Calve-Perthes disease. Introduction: Bisphosphonate therapy has gained significant attention for the treatment of ischemic osteonecrosis of the femoral head (IOFH) because of its ability to inhibit osteoclastic bone resorption, which has been shown to contribute to the pathogenesis of femoral head deformity. Because IOFH is a localized condition, there is a need to explore the therapeutic potential of local, intraosseous administration of bisphosphonate to prevent the femoral head deformity. The purpose of this study was to investigate the distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted head. Materials and Methods: IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject 14C-labeled or unlabeled ibandronate directly into the infarcted head. 14C-ibandronate injected heads were assessed after 48 h, 3 weeks, or 7 weeks later to determine the distribution and retention of the drug using autoradiography and liquid scintillation analysis. Femoral heads injected with unlabeled ibandronate were assessed at 7 weeks to determine the degree of deformity using radiography and histomorphometry. Results: Autoradiography showed that 14C-Ibandronate was widely distributed in three of the four heads examined at 48 h after the injection. Liquid scintillation analysis showed that most of the drug was retained in the injected head, and almost negligible amount of radioactivity was present in the bone and organs elsewhere at 48 h. At 3 and 7 weeks, 50% and 30% of the 14C-drug were found to be retained in the infarcted heads, respectively. Radiographic and histomorphometric assessments showed significantly better preservation of the infarcted heads treated with intraosseous administration of ibandronate compared with saline (p < 0.001). Conclusions: This study provides for the first time the evidence that local intraosseous administration is an effective route to deliver and distribute ibandronate in the infarcted femoral head to preserve the femoral head structure after ischemic osteonecrosis. In a localized ischemic condition such as IOFH, local administration of bisphosphonate may be preferable to oral or systemic administration because it minimizes the distribution of the drug to the rest of the skeleton and bypasses the need for having a restored blood flow to the infarcted head for the delivery of the drug. [source] 2423: Compartment syndrome in glaucoma damage, a new hypothesis?ACTA OPHTHALMOLOGICA, Issue 2010S ORGUL Purpose To evaluate the potential similarities in pathophysiology between non-arteritic anterior ischemic optic neuropathy (AION) and primary open-angle glaucoma (POAG). Methods The currently accepted views of the pathophysiology of AION and general understanding of the clinical picture of this ischemic condition were reviewed. Based on the hypothesis of the group in Wisconsin, who postulated a compartment syndrome of the anterior optic nerve within the tight anatomical structures of the lamina cribrosa, parallels were drawn for glaucomatous optic neuropathy, and a new hypothesis for the pathogenesis of the latter condition was suggested. Results The tight structures around, but also within the "disk at risk" observed in a majority of patients with AION are well compatible with the hypothesis of a compartment syndrome. Similar conditions may result from the restructuring process within the lamina cribrosa in POAG and lead to locally limited, but repeated "AION-like" processes, explaining why some patients progress despite reduced intraocular pressure. Conclusion The pathophysiology of POAG, especially in advanced cases, and AION seem to present similarities, which need to be better understood. [source] Microvascular Perfusion and Transport in the Diabetic HeartMICROCIRCULATION, Issue 3 2000PAUL F. McDONAGH ABSTRACT Diabetes is a chronic disease of metabolic dysfunction that is increasing worldwide. The hyperglycemia associated with diabetes causes significant protein alterations and an oxidative stress. In the heart, all cell types are affected by diabetes; the myocyte, the vasculature and the blood cells. Four out of five diabetics die from ischemic heart disease and stroke, suggesting that the diabetic is quite vulnerable to ischemic injury. It is important to understand the pathophysiologic changes that occur in the diabetic heart in order to develop thoughtful treatments to limit this serious complication. This review focuses on the anatomical and functional alterations that occur in the diabetic circulation of the heart, with emphasis on the coronary microcirculation. Coronary microvascular dysfunction combined with blood cellular alterations are presented to explain the amplified oxidative stress that occurs in the diabetic heart under ischemic conditions. [source] Metabolic costs of force generation for constant-frequency and catchlike-inducing electrical stimulation in human tibialis anterior muscleMUSCLE AND NERVE, Issue 3 2002Aivaras Ratkevicius PhD Abstract Metabolic costs of force generation were compared for constant-frequency and catchlike-inducing electrical stimulation. Repetitive catchlike-inducing trains consisted of 2 interpulse intervals (IPIs) at 12.5 ms, 1 IPI at 25 ms, and 5 IPIs at 50 ms. Constant-frequency trains consisted of 8 IPIs at 37.5 ms. One train was delivered to the peroneal nerve every 2.5 s for 36 times under ischemic conditions. Anaerobic adenosine triphosphate (ATP) turnover was determined using 31-phosphorus magnetic resonance spectroscopy (P-MRS) of the human tibialis anterior muscle. Compared with constant-frequency trains, catchlike-inducing trains produced a faster force generation and were more effective in maintaining the force,time integral as well as peak force. However, ATP costs of force generation were similar for the catchlike-inducing and constant-frequency stimulation (6.7 ± 1.1 and 6.6 ± 1.0 ,mol ATP/kg wet weight/N·s, respectively, P = 0.601). This suggests that the positive effects of catchlike-inducing stimulation on force maintenance are mediated by potentiated Ca2+ release from the sarcoplasmic reticulum rather than by lower metabolic costs of muscle force generation. Our findings also suggest that catchlike-inducing stimulation produces larger forces in fatigued muscle than constant-frequency trains and thus may be beneficial for muscle training or rehabilitation when muscle loading needs to be maintained in repetitive contractions. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source] | ||||||||||