A RECENT REVIEW ON NASAL MICROEMULSION FOR TREATMENT OF CNS DISORDER

Nasal route is found to be valuable for targeting drugs to CNS via a different mechanism. The advantages, disadvantages, various aspects of nasal anatomy and physiology, mechanism of drug transport from nose brain, drug selection criteria to cross BBB/Blood-CSF barrier are discussed briefly. Nowadays many drugs have better systemic bioavailability through nasal route as compared to oral administration. In addition, intranasal drug delivery enables dose reduction, rapid attainment of therapeutic blood levels, quicker onset of pharmacological activity, and fewer side effects. There are various approaches in delivering a therapeutic substance to the target site. One such approach is using microemulsion as a carrier for the drug. The main purpose of this study is the use of microemulsion technology in drug targeting to the brain along with mechanism of the nose to brain transport, formulation and formation of the microemulsion and its characterization

Extraction, Characterization and Evaluation of Okara Mucilage

Mucilage is the thick, gluey substances produced by nearly all plant and some microorganisms. Okra mucilage is extracted from the plant of the malavaceae [A. esculantus]. Which is originally from Egypt, but it also in cropped in southern Asia elsewhere for nutritional purposes. Their use as potential reinforcement in polymer composites requires the understanding of their microstructure and mechanical properties. This work investigates the extraction methods, solubility behavior, TLC, loss on drying, ash value, FTIR spectra, surface tension, organoleptic properties. Extracted mucilage is soluble in warm water while insoluble in organic solvents. This can shows that it safely used in dosage form without causing any adverse effect. Keywords: Okara Mucilage, Pharmaceutical Excipients, Controlled-Release Formulatio

Beta-amyloid deposition and Alzheimer's type changes induced by Borrelia spirochetes

The pathological hallmarks of Alzheimer's disease (AD) consist of P-amyloid plaques and neurofibrillary tangles in affected brain areas. The processes, which drive this host reaction are unknown. To determine whether an analogous host reaction to that occurring in AD could be induced by infectious agents, we exposed mammalian glial and neuronal cells in vitro to Borrelia burgdorferi spirochetes and to the inflammatory bacterial lipopolysaccharide (LPS). Morphological changes analogous to the amyloid deposits of AD brain were observed following 2-8 weeks of exposure to the spirochetes. Increased levels of beta-amyloid presursor protein (A beta PP) and hyperphosphorylated tau were also detected by Western blots of extracts of cultured cells that had been treated with spirochetes or LPS. These observations indicate that, by exposure to bacteria or to their toxic products, host responses similar in nature to those observed in AD may be induced. (C) 2005 Elsevier Inc. All rights reserved

Using regulatory variants to detect gene-gene interactions identifies networks of genes linked to cell immortalization

The extent to which the impact of regulatory genetic variants may depend on other factors, such as the expression levels of upstream transcription factors, remains poorly understood. Here we report a framework in which regulatory variants are first aggregated into sets, and using these as estimates of the total cis-genetic effects on a gene we model their non-additive interactions with the expression of other genes in the genome. Using 1220 lymphoblastoid cell lines across platforms and independent datasets we identify 74 genes where the impact of their regulatory variant-set is linked to the expression levels of networks of distal genes. We show that these networks are predominantly associated with tumourigenesis pathways, through which immortalised cells are able to rapidly proliferate. We consequently present an approach to define gene interaction networks underlying important cellular pathways such as cell immortalisation

A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage

ML, CD, IvL, GP, TM, SD, MS, APF, CT, DL, MAH, KL and SL: project grants from the Swedish Research Council, the Swedish Cancer Society and the Swedish Childhood Cancer Foundation. MHi and JC: Cancer Research UK (C8/A6613). MC, EP and WE: Wellcome Trust (073915). MN and BV: projects MEYS-NPS-LO1413 and GACR P206/12/G151. EMC, MP, MMS, ZF and PG: Norwegian Cancer Society (182735, 732200) and Helse Vest (911884, 911789). RB and SC: NIH (R01 CA95684), the Leukemia and Lymphoma Society and the Waxman Foundation. NW, AH, Ad’H: Cancer Research UK (C21383/A6950) and Engineering and Physical Sciences Research Council Doctoral Training Program. JL and YZ: Cancer Research UK (C240/A15751). MH and BW: SARomics Biostructures ABUY, KF: DDDP SciLife, Sweden. LJ, MHa, RS and A-LG: CBCS, Sweden. VP: SciLife fellowship. AT: Breast Cancer Research Scotland.The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex. Twelve other DHODH inhibitor chemotypes are detailed among the p53 activators, which identifies DHODH as a frequent target for structurally diverse compounds. We observe that HZ compounds accumulate cancer cells in S-phase, increase p53 synthesis, and synergize with an inhibitor of p53 degradation to reduce tumor growth in vivo. We, therefore, propose a strategy to promote cancer cell killing by p53 instead of its reversible cell cycle arresting effect.Publisher PDFPeer reviewe

Feasibility of a walking virtual reality system for rehabilitation: objective and subjective parameters

[EN] Background: Even though virtual reality (VR) is increasingly used in rehabilitation, the implementation of walking navigation in VR still poses a technological challenge for current motion tracking systems. Different metaphors simulate locomotion without involving real gait kinematics, which can affect presence, orientation, spatial memory and cognition, and even performance. All these factors can dissuade their use in rehabilitation. We hypothesize that a marker-based head tracking solution would allow walking in VR with high sense of presence and without causing sickness. The objectives of this study were to determine the accuracy, the jitter, and the lag of the tracking system and its elicited sickness and presence in comparison of a CAVE system. Methods: The accuracy and the jitter around the working area at three different heights and the lag of the head tracking system were analyzed. In addition, 47 healthy subjects completed a search task that involved navigation in the walking VR system and in the CAVE system. Navigation was enabled by natural locomotion in the walking VR system and through a specific device in the CAVE system. An HMD was used as display in the walking VR system. After interacting with each system, subjects rated their sickness in a seven-point scale and their presence in the Slater-Usoh-Steed Questionnaire and a modified version of the Presence Questionnaire. Results: Better performance was registered at higher heights, where accuracy was less than 0.6 cm and the jitter was about 6 mm. The lag of the system was 120 ms. Participants reported that both systems caused similar low levels of sickness (about 2.4 over 7). However, ratings showed that the walking VR system elicited higher sense of presence than the CAVE system in both the Slater-Usoh-Steed Questionnaire (17.6 +/- 0.3 vs 14.6 +/- 0.6 over 21, respectively) and the modified Presence Questionnaire (107.4 +/- 2.0 vs 93.5 +/- 3.2 over 147, respectively). Conclusions: The marker-based solution provided accurate, robust, and fast head tracking to allow navigation in the VR system by walking without causing relevant sickness and promoting higher sense of presence than CAVE systems, thus enabling natural walking in full-scale environments, which can enhance the ecological validity of VR-based rehabilitation applications.The authors wish to thank the staff of LabHuman for their support in this project, especially José Miguel Martínez and José Roda for their assistance. 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Astrocytes secrete a factor inducing the expression of HT7-protein and neurothelin in endothelial cells of chorioallantoic vessels

Among the most specific markers of the blood-brain barrier phenotype of endothelial cells are the well-characterized immunoglobulin-like surface glycoprotein HT7 and the probably related or identical glycoprotein neurothelin. Both can be induced in chorioallantoic vessels by transplants of embryonic mouse brain. Other blood-brain barrier markers have been shown to be inducible by type-1 astrocytes in endothelial cells of non-neural origin. In the present work we tested the hypothesis that this cellular interaction between astrocytes and endothelial cells is mediated by a soluble factor(s). Chorioallantoic vessels of embryonic day 9 chick embryos were exposed for 4 or 10 days to a constant and localized delivery of astrocyte-conditioned medium by using a piece of gelfoam posed onto the chorioallantoic membrane, as a localized reservoir, which was connected to a miniosmotic pump system delivering astrocyte-conditioned medium at a steady rate. We found that in a significant number of chorioallantoic vessels located near the gelfoam, endothelial cells exposed to astrocyte-conditioned medium for a period of 4 or 10 days, but not to glioma-, fibroblast- or endothelial cell-derived conditioned medium, expressed the HT7 antigen and neurothelin. These results provide evidence that type-1-astrocytes are capable of inducing blood-brain barrier related properties in endothelial cells of non-neural origin through a soluble factor(s

Heterogeneity of Microvascular Endothelial Cells of the Brain: A Comparison of the Effects of Extracellular Matrix and Soluble Astrocytic Factors

Until recently, microvascular endothelial cells of the blood-brain barrier were considered a homogeneous population, whose properties were induced by astrocytes. To address the question of brain endothelial cell heterogeneity, we measured the activity of specific markers of endothelial cells of different origins, including two brain-derived endothelial cell lines grown on plastic or on extracellular matrix (ECM) components secreted either by a glial or a fibroblast cell line, with or without the addition of astrocyte-conditioned medium (ACM). ECM components and ACM conjointly, but differently in each endothelial cell line, increased the uptake of leucine and modulated the expression of the specific markers alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) in both cerebral endothelial lines. ACM decreased the incorporation of thymidine in the pulmonary endothelial cell line, but not in a cerebral cell line. An induction of blood-brain barrier specific GGTP was never observed in endothelial cells of non-cerebral origin. These results demonstrate that subpopulations of cerebral endothelial cells exist, that astrocyte-derived soluble factors and ECM components can modulate the expression and the function of markers of endothelial cells and that astrocyte-derived soluble factors have a selective growth inhibitory effect on endothelial cells of non-cerebral origi

Induction of the blood-brain barrier specific HT7 and neurothelin epitopes in endothelial cells of the chick chorioallantoic vessels by a soluble factor derived from astrocytes.

Some blood-brain barrier properties of microvascular endothelial cells have been shown to be inducible by astrocytes. We tested the hypothesis that this cellular interaction is mediated by a soluble factor(s). Chick chorioallantoic vessels in ovo were constantly exposed to astrocyte-conditioned medium. We found that endothelial cells exposed to astrocyte-derived factors, but not to glioma- or endothelial cell-derived factors, expressed the HT7 antigen and neurothelin, two specific markers of the blood-brain barrier phenotype. These results indicate that a soluble factor(s) secreted by astrocytes is capable to induce specific blood-brain barrier properties in endothelial cells of non-neural origin