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201.
Nahla Salah Barakat 《AAPS PharmSciTech》2010,11(3):1138-1146
In view of the good skin tolerability, glycofurol was used as a vehicle-based gel, and its effect in the topical penetration
of Naproxen (NAP) was investigated. The aims of this study were to develop a suitable gel with bioadhesive property, spreadability,
and viscosity for topical anti-inflammatory effect. Three gelling and adhesive agents were examined: Carbopol 974P, Gantrez
AN 119, and polyvinylpyrollidone K30. Skin permeation rates and lag times of NAP were evaluated using the Franz-type diffusion
cell in order to optimize the gel formulation. The permeation rate of NAP-based gel across the excised rat skin was investigated.
A significant increase in permeability parameters such as steady-state flux (J
ss), permeability coefficient (K
p), and penetration index (PI) was observed in optimized formulation containing 2% Transcutol as an permeation enhancer. From
skin irritation test, it was concluded that the optimized novel glycofurol-based gel formulation was safe to be used for topical
drug delivery. The developed glycofurol-based gel appeared promising for dermal and transdermal delivery of naproxen and could
be applicable with water-insoluble drugs, which would circumvent most of the problems associated with drug therapy. 相似文献
202.
Amina Bakhchane Majida Charif Sara Salime Redouane Boulouiz Halima Nahili Rachida Roky Guy Lenaers Abdelhamid Barakat 《PloS one》2015,10(9)
Mutations in the TBC1D24 gene are responsible for four neurological presentations: infantile epileptic encephalopathy, infantile myoclonic epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and NSHL (non-syndromic hearing loss). For the latter, two recessive (DFNB86) and one dominant (DFNA65) mutations have so far been identified in consanguineous Pakistani and European/Chinese families, respectively. Here we report the results of a genetic study performed on a large Moroccan cohort of deaf patients that identified three families with compound heterozygote mutations in TBC1D24. Four novel mutations were identified, among which, one c.641G>A (p.Arg214His) was present in the three families, and has a frequency of 2% in control Moroccan population with normal hearing, suggesting that it acts as an hypomorphic variant leading to restricted deafness when combined with another recessive severe mutation. Altogether, our results show that mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco, and that due to its possible compound heterozygote recessive transmission, this gene should be further considered and screened in other deaf cohorts. 相似文献
203.
Craddock TJ St George M Freedman H Barakat KH Damaraju S Hameroff S Tuszynski JA 《PloS one》2012,7(6):e37251
The cytoskeleton is essential to cell morphology, cargo trafficking, and cell division. As the neuronal cytoskeleton is extremely complex, it is no wonder that a startling number of neurodegenerative disorders (including but not limited to Alzheimer's disease, Parkinson's disease and Huntington's disease) share the common feature of a dysfunctional neuronal cytoskeleton. Recently, concern has been raised about a possible link between anesthesia, post-operative cognitive dysfunction, and the exacerbation of neurodegenerative disorders. Experimental investigations suggest that anesthetics bind to and affect cytoskeletal microtubules, and that anesthesia-related cognitive dysfunction involves microtubule instability, hyper-phosphorylation of the microtubule-associated protein tau, and tau separation from microtubules. However, exact mechanisms are yet to be identified. In this paper the interaction of anesthetics with the microtubule subunit protein tubulin is investigated using computer-modeling methods. Homology modeling, molecular dynamics simulations and surface geometry techniques were used to determine putative binding sites for volatile anesthetics on tubulin. This was followed by free energy based docking calculations for halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) on the tubulin body, and C-terminal regions for specific tubulin isotypes. Locations of the putative binding sites, halothane binding energies and the relation to cytoskeleton function are reported in this paper. 相似文献
204.
Dvoriantchikova G Ivanov D Barakat D Grinberg A Wen R Slepak VZ Shestopalov VI 《PloS one》2012,7(2):e31991
Pannexin1 (Panx1) forms large nonselective membrane channel that is implicated in paracrine and inflammatory signaling. In vitro experiments suggested that Panx1 could play a key role in ischemic death of hippocampal neurons. Since retinal ganglion cells (RGCs) express high levels of Panx1 and are susceptible to ischemic induced injury, we hypothesized that Panx1 contributes to rapid and selective loss of these neurons in ischemia. To test this hypothesis, we induced experimental retinal ischemia followed by reperfusion in live animals with the Panx1 channel genetically ablated either in the entire mouse (Panx1 KO), or only in neurons using the conditional knockout (Panx1 CKO) technology. Here we report that two distinct neurotoxic processes are induced in RGCs by ischemia in the wild type mice but are inactivated in Panx1KO and Panx1 CKO animals. First, the post-ischemic permeation of RGC plasma membranes is suppressed, as assessed by dye transfer and calcium imaging assays ex vivo and in vitro. Second, the inflammasome-mediated activation of caspase-1 and the production of interleukin-1β in the Panx1 KO retinas are inhibited. Our findings indicate that post-ischemic neurotoxicity in the retina is mediated by previously uncharacterized pathways, which involve neuronal Panx1 and are intrinsic to RGCs. Thus, our work presents the in vivo evidence for neurotoxicity elicited by neuronal Panx1, and identifies this channel as a new therapeutic target in ischemic pathologies. 相似文献
205.
A Mutation in PNPT1, Encoding Mitochondrial-RNA-Import Protein PNPase,Causes Hereditary Hearing Loss
Simon von?Ameln Geng Wang Redouane Boulouiz Mark?A. Rutherford Geoffrey?M. Smith Yun Li Hans-Martin Pogoda Gudrun Nürnberg Barbara Stiller Alexander?E. Volk Guntram Borck Jason?S. Hong Richard?J. Goodyear Omar Abidi Peter Nürnberg Kay Hofmann Guy?P. Richardson Matthias Hammerschmidt Tobias Moser Bernd Wollnik Carla?M. Koehler Michael?A. Teitell Abdelhamid Barakat Christian Kubisch 《American journal of human genetics》2012,91(5):919-927
206.
Thirkill TL Hendren SR Soghomonians A Mariano NF Barakat AI Douglas GC 《Cell communication and signaling : CCS》2004,2(1):4
Background
In human and non-human primates, migratory trophoblasts penetrate the uterine epithelium, invade uterine matrix, and enter the uterine vasculature. Invasive trophoblasts show increased expression of β1 integrin. Since trophoblast migration within the uterine vasculature involves trophoblast attachment to endothelial cells lining the vessel walls, this raises the possibility that cell-cell contact and/or factors released by endothelial cells could regulate trophoblast integrin expression. To test this, we used an in vitro system consisting of early gestation macaque trophoblasts co-cultured on top of uterine microvascular endothelial cells. 相似文献207.
Ye Z Guo L Barakat KJ Pollard PG Palucki BL Sebhat IK Bakshi RK Tang R Kalyani RN Vongs A Chen AS Chen HY Rosenblum CI MacNeil T Weinberg DH Peng Q Tamvakopoulos C Miller RR Stearns RA Cashen DE Martin WJ Metzger JM Strack AM MacIntyre DE Van der Ploeg LH Patchett AA Wyvratt MJ Nargund RP 《Bioorganic & medicinal chemistry letters》2005,15(15):3501-3505
A novel isoquinuclidine containing selective melanocortin subtype-4 receptor small molecule agonist, 3 (RY764), is reported. Its in vivo characterization revealed mechanism-based food intake reduction and erectile activity augmentation in rodents. 相似文献
208.
Extensive duplication and reshuffling in the Arabidopsis genome 总被引:15,自引:0,他引:15
Systematic analysis of the Arabidopsis genome provides a basis for detailed studies of genome structure and evolution. Members of multigene families were mapped, and random sequence alignment was used to identify regions of extended similarity in the Arabidopsis genome. Detailed analysis showed that the number, order, and orientation of genes were conserved over large regions of the genome, revealing extensive duplication covering the majority of the known genomic sequence. Fine mapping analysis showed much rearrangement, resulting in a patchwork of duplicated regions that indicated deletion, insertion, tandem duplication, inversion, and reciprocal translocation. The implications of these observations for evolution of the Arabidopsis genome as well as their usefulness for analysis and annotation of the genomic sequence and in comparative genomics are discussed. 相似文献
209.
210.
Hamid Barakat Anne-Marie Geneviere-Garrigues Philippe Schatt Andr Picard 《Biology of the cell / under the auspices of the European Cell Biology Organization》1994,81(3):205-213
Summary— Shortening of aster-nucleated microtubules is a mitotic feature, which is proportional to the M-phase promoting factor kinase activity. We have taken advantage of this characteristic to appraise the mitotic status of cytoplasmic territories in polyspermic starfish oocytes. In early prometaphase, asters are small in the nuclear area, where cyclin B accumulated before GVBD, while in the remaining of the oocytes asters are large. In metaphase all asters are small. This coincides with a change in behaviour of cyclin B, whose association with microtubules increases in late prometaphase. We discuss the possibility that uneven distribution of cyclin B-dependent kinase is a general feature of mitosis and that it allows the cell to build the convenient spindle at the right place. 相似文献