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71.
Hala Bakr El-Nassan Aliaa Nabil ElMeshad Walaa Wadie Rabab H. Sayed 《Pharmaceutical research》2018,35(8):149
Purpose
To assess the gelation power of N-palmitoyl L-alanine derivatives in injectable oils and to use the best chosen organogel as parenteral implant of granisetron for the treatment of emesis.Methods
Twelve N-palmitoyl L-alanine derived organogels were developed and evaluated in terms of morphology, thermal properties and in vivo performance. The ability of the selected formula to form in situ gel upon subcutaneous injection in rats and its biocompatibility were monitored over 2 weeks by histopathological examination of the injection site.Results
The acid derivative (N-palmitoyl L-alanine; PA) was superior to ester derivatives. The chosen formula (PA/safflower oil 10% w/v) was successful in forming an in situ gel of granisetron when subcutaneously injected in rats, lasting for 2 weeks and proved to be biocompatible by histopathological examination. Moreover, it exerted an extended antiemetic activity by decreasing the cisplatin-induced pica for a duration of 96 h and reduced preprotachykinin A mRNA expression and Substance P level for up to 4 days (gastric tissue) or 5 days (medulla oblongata) in rats.Conclusion
Granisetron organogel could be considered as a safe, sustained-release and supportive anticancer treatment in both acute and chronic emesis as well as an accompanying treatment with chemotherapeutics in cancer cases.72.
Högberg C Gidlöf O Deflorian F Jacobson KA Abdelrahman A Müller CE Olde B Erlinge D 《Thrombosis and haemostasis》2012,108(1):119-132
Farnesyl pyrophosphate (FPP) is an intermediate in cholesterol biosynthesis, and it has also been reported to activate platelet LPA (lysophosphatidic acid) receptors. The aim of this study was to investigate the role of extracellular FPP in platelet aggregation. Human platelets were studied with light transmission aggregometry, flow cytometry and [3?S]GTPγS binding assays. As shown previously, FPP could potentiate LPA-stimulated shape change. Surprisingly, FPP also acted as a selective insurmountable antagonist to ADP-induced platelet aggregation. FPP inhibited ADP-induced expression of P-selectin and the activated glycoprotein (Gp)IIb/IIIa receptor. FPP blocked ADP-induced inhibition of cAMP accumulation and [3?S]GTPγS binding in platelets. In Chinese hamster ovary cells expressing the P2Y?? receptor, FPP caused a rightward shift of the [3?S]GTPγS binding curve. In Sf9 insect cells expressing the human P2Y?? receptor, FPP showed a concentration-dependent, although incomplete inhibition of [3H]PSB-0413 binding. Docking of FPP in a P2Y?? receptor model revealed molecular similarities with ADP and a good fit into the binding pocket for ADP. In conclusion, FPP is an insurmountable antagonist of ADP-induced platelet aggregation mediated by the P2Y?? receptor. It could be an endogenous antithrombotic factor modulating the strong platelet aggregatory effects of ADP in a manner similar to the use of clopidogrel, prasugrel or ticagrelor in the treatment of ischaemic heart disease. 相似文献
73.
74.
Aliaa H. Abdelhakim Kristen E. Dunbar Kyle J. Godfrey Cristina Abascal Ananza David N. Silvers Michael Kazim 《Orbit (Amsterdam, Netherlands)》2013,32(4):274-278
Purpose: Dermatofibromas are common cutaneous lesions, but rarely occur in the eyelid skin. The reason for the low incidence in the palpebral skin has not been elucidated. In this study, we analyze the histopathologic features of an illustrative case of dermatofibroma and review previously published cases to determine whether eyelid dermatofibroma develops differently from the prototypical dermatofibroma.Methods: Histopathologic analysis of a new illustrative case of eyelid dermatofibroma and retrospective review of published cases.Results: The distinguishing features of the illustrative lesion included a rounder gross appearance, nonacanthotic epithelium, basophilic staining, cellular character, and a paucity of “collagen trapping.” These features deviated from the typical features associated with classic dermatofibroma. Review of the 11 previously published cases of eyelid dermatofibroma revealed that they were more similar in appearance to the illustrative lesion than to classic dermatofibroma.Discussion: The rarity and histological deviations of the eyelid dermatofibroma suggest that the dermal substrate from which the lesion develops differs from that of the classic dermatofibroma. This difference may be explained microanatomically based on the fact that the dermis of the eyelid is predominantly papillary, whereas the dermis of extrapalpebral skin where dermatofibromas are more common is predominantly reticular.Conclusions: Although related, eyelid dermatofibromas appear to be histologically distinct from classic dermatofibromas, owing to the unique dermal composition of the site of origin. 相似文献
75.
Afaf K. El-Ansary Aliaa M. Kamal Mokhtar AbdHafiz Al-Ghorafi 《Medicinal chemistry research》2013,22(6):2589-2601
Design and synthesis of some new thienopyridazine derivatives as anticancer agents were the goal of this work. Accordingly, a series of novel compounds were synthesized via reacting thienopyridazine carboxylic acid hydrazide with different organic reagents. Twelve novel compounds were selected by National Cancer Institute for a full anticancer screening assay where seven of the investigated compounds showed non-selective broad spectrum and promising activity almost against all cancer cell lines. One of the most active compounds was chosen to be evaluated against 60-cell line panel at five concentration levels and revealed a remarkable growth inhibition activity. 相似文献
76.
Correlation of pH probe-measured laryngopharyngeal reflux with symptoms and signs of reflux laryngitis 总被引:12,自引:0,他引:12
OBJECTIVES/HYPOTHESIS: Laryngitis secondary to gastric acid reflux is a prevalent, yet incompletely understood, otolaryngological disorder. Further characterization of the relationship between symptoms and signs and reflux severity is needed. STUDY DESIGN: Prospective clinical trial. METHODS: Forty-two consecutive, nonsmoking patients with one or more reflux laryngitis symptoms were recruited to complete a symptom questionnaire, videostrobolaryngoscopy, and 24-hour, dual-sensor pH probe testing. Twenty-nine patients had more than four episodes of laryngopharyngeal reflux, and the remaining 13 served as control subjects. Symptom scores were produced by multiplying the severity by the frequency for the following: hoarseness, throat pain, "lump-in-throat" sensation, throat clearing, cough, excessive phlegm, dysphagia, odynophagia, and heartburn. Endoscopic laryngeal signs included erythema and edema of the vocal folds and arytenoids, and interarytenoid irregularity. RESULTS: Symptom scores varied significantly, with throat clearing being greater than the rest. None of the symptoms, except heartburn, correlated with reflux (laryngopharyngeal and esophageal) severity. Patients with worse laryngopharyngeal reflux were found to have worse esophageal reflux. Endoscopic laryngeal signs were rated as mild, on average, and did not correlate with laryngopharyngeal reflux severity. The number of laryngopharyngeal reflux episodes (per 24 h) ranged from 0 to 40 (mean number, 10.6 episodes). CONCLUSIONS: Throat clearing was the most intense symptom in the present group of patients with proven reflux laryngitis. Dual-sensor pH probe testing could not predict the severity of patient's reflux laryngitis symptoms or signs. Only the heartburn symptom correlated with laryngopharyngeal and esophageal reflux. 相似文献
77.
The gastrointestinal uptake of different crystal structures of TiO2 was investigated using Caco-2 intestinal cells. Caco-2 monolayers exhibited time-dependent, saturable uptake of Ti from TiO2 exposures of 1 mg l−1 over 24 h, which was influenced by crystal type. Initial uptake rates were 5.3, 3.73, 3.58 and 4.48 nmol mg−1 protein h−1 for bulk, P25, anatase and rutile forms respectively. All exposures caused elevations of Ti in the cells relative to the control (ANOVA P < 0.05). Electron micrographs of the Caco-2 monolayer showed the presence of particles inside the cells, and energy dispersive spectroscopy (EDS) confirmed the composition as TiO2. Incubating the cells with 120 IU nystatin (putative endocytosis inhibitor) or 100 μmol l−1 vanadate (ATPase inhibitor) caused large increases in Ti accumulation for all crystal types relative to controls (ANOVA P < 0.05), except for the rutile form with vanadate. Incubating the cells with 90 μmol l−1 genistein (tyrosine kinase inhibitor) or 27 μmol l−1 chloropromazine (clathrin-mediated endocytosis inhibitor) caused a large decrease in Ti accumulation relative to the controls (ANOVA P < 0.05). Cell viability measures were generally good (low LDH leak, normal cell morphology), but there were some changes in the electrolyte composition (K+, Na+, Ca2+, Mg2+) of exposed cells relative to controls. A rise in total Ca2+ concentration in the cells was observed for all TiO2 crystal type exposures. Overall, the data shows that Ti accumulation for TiO2 NP exposure in Caco-2 cells is crystal structure-dependent, and that the mechanism(s) involves endocytosis of intact particles. 相似文献
78.
Shahira M. Ezzat Maha M. Salama Aliaa N. ElMeshad Mahmoud H. Teaima Laila A. Rashad 《Archives of pharmacal research》2016,39(7):912-925
The anti-wrinkle activity of defatted rosemary extract (DER) was assessed, and its effect was optimized by encapsulation in transferosomes (TFs). DER was standardized to a rosmarinic acid content of 4.58 ± 0.023 mg% using reversed-phase high performance liquid chromatography (Rp-HPLC), and its components were identified by HPLC-diode array detection-tandem mass spectrometry. In vitro free radical scavenging assays showed DER had high free radical scavenging activity against 2,2-diphenyl-2-picryl hydrazyl, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and superoxide radicals. DER also inhibited bleaching of β-carotene with high Fe(III) and Fe(II) chelating ability. In vivo anti-wrinkle activities of topically applied DER (20, 50, and 100 mg) and a TF formulation (TF4, 20 mg of DER) were evaluated in UVB-irradiated mice using a wrinkle scoring method, metalloproteinase (MMP) expression, and histopathology. Among the nanovesicles, TF4 was the most deformable, and had an acceptable size and encapsulation efficiency and enhanced permeation of DER through rat skin compared with unencapsulated DER. DER (50 and 100 mg) and TF4 significantly inhibited MMP-2 and MMP-9 expression and improved wrinkle scores. DER and TF4 moderately decreased epidermal thickness without pigmentation. DER is a potent natural antioxidant for combating skin aging. Moreover, encapsulation of DER in TFs will enhance its skin permeation and anti-wrinkle activity. 相似文献