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161.
Mohammed Ali Kassem Mona Hassan Aboul-Einien Mai Magdy El Taweel 《AAPS PharmSciTech》2018,19(5):2155-2173
Felodipine has a very low bioavailability due to first-pass metabolism. The aim of this study was to enhance its bioavailability by transdermal application. Felodipine-loaded transferosomes were prepared by thin-film hydration using different formulation variables. An optimized formula was designed using statistical experimental design. The independent variables were the used edge activator, its molar ratio to phosphatidylcholine, and presence or absence of cholesterol. The responses were entrapment efficiency of transferosomes, their size, polydispersity index, zeta potential, and percent drug released after 8 h. The optimized formula was subjected to differential scanning calorimetry studies and its stability on storage at 4°C for 6 months was estimated. This formula was improved by incorporation of different permeation enhancers where ex vivo drug flux through mice skin was estimated and the best improved formula was formulated in a gel and lyophilized. The prepared gel was subjected to in vivo study using Plendil® tablets as a reference. According to the calculated desirability, the optimized transferosome formula was that containing sodium deoxycholate as edge activator at 5:1 M ratio to phosphatidylcholine and no cholesterol. The thermograms of this formula indicated the incorporation of felodipine inside the prepared vesicles. None of the tested parameters differed significantly on storage. The lyophilized gel of labrasol-containing formula was chosen for in vivo study. The relative bioavailability of felodipine from the designed gel was 1.7. In conclusion, topically applied lyophilized gel containing felodipine-loaded transferosomes is a promising transdermal delivery system to enhance its bioavailability. 相似文献
162.
Ibrahim M. Abdel‐Salam Abeer M. Ashmawy Amany M. Hilal Omayma A. Eldahshan Mohamed Ashour 《化学与生物多样性》2018,15(8)
Breast cancer constitutes the second most prevalent cancer in Egypt, the problem needs more trends in treatment and treatment development either by regimen modification or introducing new drugs, and the main objective of this study is to screen the effects of the aqueous ethanol herbal extract of Luffa cylindrica leaves on different types of breast cancer cell lines representing different molecular subtypes of the disease. The major active constituents of the extract were tentatively identified by LC/MS which revealed the presence of phenolic compound derivatives and saponin that may be responsible in part for the activity of the extract. The emphasis was laid on the main apoptotic pathways as well as the extract effect on the normal cell line. Results of phytochemical investigation, cell cycle analysis, and molecular analysis of apoptotic and proliferative markers have shown effective anticancer activity against MCF‐7, BT‐474, and MDA‐MB‐231 cell lines which represent three subtypes of breast cancer, luminal A, luminal B, and triple negative, respectively. On the other hand, the effects on normal lung fibroblast cell line are less prominent at the dose used for treating breast cancer cell lines. 相似文献
163.
MIF‐173G/C (rs755622) polymorphism as a risk factor for acute lymphoblastic leukemia development in children
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Background
Macrophage inhibitory factor (MIF) is a pro‐inflammatory cytokine modulating monocyte motility and a pleiotropic regulator of different biological and cellular processes. The MIF‐173G/C (rs755622) polymorphism is found in the promoter region and affects its activity. The present study investigated the MIF polymorphism as a risk factor for the development of acute lymphoblastic leukemia (ALL) in Egyptian children.Methods
We analyzed the MIF‐173G/C (rs755622) polymorphism in 180 ALL cases and 150 healthy control children by amplification of the gene using a polymerase chain reaction followed by restriction endonuclease digestion and running on an agarose gel for visualization of the product.Results
We found a significant incidence of the homozygous polymorphic (CC) genotype and the combined polymorphic genotypes (GC + CC) in ALL patients compared to healthy controls (p = 0.001 and p = 0.007, respectively), whereas the wild‐type genotype (GG) was more common in healthy controls (p = 0.006). Multivariate logistic regression analysis adjustment for MIF different genotypes and other potential risk factors such as age, sex and parental smoking indicated that the CC genotype is the only significant risk factor for the test (p = 0.02). We also noted that, by increasing the C‐allele representation within the gene [GC, CC], there was an increase in total leukocytic count (p = 0.09 and p = 0.001, respectively) that may reflect the bad prognostic impact of the polymorphic allele, although further studies are needed.Conclusions
The results of the present study indicate that the MIF‐173G/C (rs755622) polymorphism is a risk factor for childhood ALL development with respect to both homozygous and combined polymorphic genotypes. In addition, the increased leukocytic count in synchronization with the increased representation of the polymorphic C‐allele may reflect its bad prognostic impact. 相似文献164.
Liquid chromatographic and spectrofluorimetric assays of empagliflozin: Applied to degradation kinetic study and content uniformity testing
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Stability‐indicating high‐performance liquid chromatography (HPLC) and spectrofluorimetric methods were developed for determination of empagliflozin (EGF). EGF was subjected to oxidation, wet heat, photo‐degradation, acid hydrolysis and alkali hydrolysis. The alkaline degradation pathway was subjected to a kinetics study as the major product obtained after stress conditions. Arrhenius plots were constructed and the activation energies of the degradation process were calculated. HPLC was used for the kinetic study as it enabled simultaneous determination of EGF and the degradation product while the spectrofluorimetric assay was applied to content uniformity testing due to its higher sensitivity and lower limit of detection (LOD). Isocratic chromatographic elution was attained for HPLC on a Intersil® C18 column (150 mm × 4 mm, 5 μm), using a mobile phase of acetonitrile–potassium dihydrogen phosphate buffer pH 4, (50:50, v/v) at a flow rate of 1 ml/min with ultraviolet (UV) detection at 225 nm. The relative fluorescence intensity was recorded by spectrofluorimeter applying synchronous mode using ?λ = 70 nm at 297.6 nm. Linearity ranges were found to be 5–50 μg/ml and 50–1000 ng/ml for HPLC and spectrofluorimetric methods, respectively. 相似文献
165.
Utility of Von Pechman synthesis of coumarin reaction for development of spectrofluorimetric method for quantitation of salmeterol xinafoate in pharmaceutical preparations and human plasma
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Mohamed Awad Mohamed A. Hammad Ahmed M. Abdel‐Megied Mahmoud A. Omar 《Luminescence》2018,33(5):913-918
Simple, precise and selective spectrofluorimetric technique was evolved for quantitation of selective β2 agonist drug namely salmeterol xinafoate (SAL). Utilizing its phenolic nature, a method was described based on the reaction of the studied drug with ethyl acetoacetate (EAA) to yield extremely fluorescent coumarin product which can be detected at 480 nm (λex = 420 nm). The procedure obeys Beer's law with a correlation coefficient of r = 0.9999 in the concentration range between 500 and 5000 ng ml?1 with and 177 ng ml?1 for limit of detection (LOD) and limit of quantification (LOQ), respectively. Diverse reaction variables influencing the firmness and formation of the coumarin product were accurately examined and modified to ensure greatest sensitivity of the procedure. The proposed technique was performed and examined according to the US Food and Drug Administration (FDA) guidelines for bio‐analytical methods and was efficiently applied for quantitation of SAL in both pharmaceutical preparations (% recovery = 100.06 ± 1.07) and spiked human plasma (% recovery = 96.64–97.14 ± 1.01–1.52). 相似文献
166.
Assessment of the potential of temporin peptides from the frog Rana temporaria (Ranidae) as anti‐diabetic agents
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Vishal Musale Bruno Casciaro Maria Luisa Mangoni Yasser H.A. Abdel‐Wahab Peter R. Flatt J. Michael Conlon 《Journal of peptide science》2018,24(2)
Temporin A (FLPLIGRVLSGIL‐NH2), temporin F (FLPLIGKVLSGIL‐NH2), and temporin G (FFPVIGRILNGIL‐NH2), first identified in skin secretions of the frog Rana temporaria, produced concentration‐dependent stimulation of insulin release from BRIN‐BD11 rat clonal β‐cells at concentrations ≥1 nM, without cytotoxicity at concentrations up to 3 μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active. Temporins A, F, and G also produced a concentration‐dependent stimulation of insulin release from 1.1B4 human‐derived pancreatic β‐cells, with temporin G being the most potent and effective, and from isolated mouse islets. The data indicate that cationicity, hydrophobicity, and the angle subtended by the charged residues in the temporin molecule are important determinants for in vitro insulinotropic activity. Temporin A and F (1 μM), but not temporin G, protected BRIN‐BD11 cells against cytokine‐induced apoptosis (P < 0.001) and augmented (P < 0.001) proliferation of the cells to a similar extent as glucagon‐like peptide‐1. Intraperitoneal injection of temporin G (75 nmol/kg body weight) together with a glucose load (18 mmol/kg body weight) in C57BL6 mice improved glucose tolerance with a concomitant increase in insulin secretion whereas temporin A and F administration was without significant effect on plasma glucose levels. The study suggests that combination therapy involving agents developed from the temporin A and G sequences may find application in Type 2 diabetes treatment. 相似文献
167.
Sekena H. Abdel-Aziem K.F. Mahrous M.A.M. Abd El-Hafez M. Abdel Mordy 《Journal of Genetic Engineering and Biotechnology》2018,16(1):89-97
The genetic polymorphisms of two functional genes named: myostatin (MSTN) and prolactin (PRL) were investigated in three goat breeds (Barki, Damascus and Zaraibi) using Sanger nucleotide sequence and restriction fragment length polymorphism (RFLP) methods, in order to differentiate between these breeds. Nucleotide sequencing of 337 bp MSTN gene detected five SNPs in Barki breed, two SNPs in Damascus breed, while the Zaraibi breed did not show any SNPs. Moreover, MSTN-HaeIII/PCR-RFLP gave a single Genotype BB was found in all the studied breeds. Meanwhile, Nucleotide sequencing of 196 bp PRL gene showed two SNPs in Damascus breed, one SNPs in Zaraibi breed, while the Barki breed did not show any SNPs. Moreover, PRL-Eco24I/PCR-RFLP showed three genotypes (AA, AB and BB). The genotype AB showed the maximum frequency in all the studied breeds (0.75, 0.85, and 0.90 for Damascus, Barki and Zaraibi breeds, respectively). Observed heterozygosity (Ho) value was higher than expected heterozygosity (He) value all studied breeds. In addition, the values of both Ho and He were the highest in Zaraibi breed (0.90 and 0.51 respectively). Chi-square (χ2) value revealed a significant variation Hardy-Weinberg equilibrium (P < .05) in the three studied breeds. It is the highest in Zaraibi goats and lowest in Damascus breed. The results demonstrated that the PRL-Eco24I/PCR-RFLP polymorphism may be utilized as effective marker for genetic differentiation between goat breeds, but MSTN-HaeIII/PCR-RFLP revealed no polymorphism or variation, thus it is not recommended in the selection program. Moreover, these results open up interesting prospects for future selection programs, especially marker assisted selection. In addition, the results established that PCR-RFLP method is a suitable tool for calculating genetic variability. 相似文献
168.
A chiral enantioseparation generic strategy for anti‐Alzheimer and antifungal drugs by short end injection capillary electrophoresis using an experimental design approach
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The present study describes a generic strategy using capillary electrophoretic (CE) method for chiral enantioseparation of anti‐Alzheimer drugs, namely, donepezil (DON), rivastigmine (RIV), and antifungal drugs, namely, ketoconazole (KET), Itraconazole (ITR), fluconazole (FLU), and sertaconazole (SRT) in which these drugs have different basic and acidic properties. Several modified cyclodextrins (CDs) were applied for enantioseparation of racemates such as highly sulfated α, γ CDs, hydroxyl propyl‐β‐CD, and Sulfobutyl ether‐β‐CD. The starting screening conditions consist of 50‐mM phosphate‐triethanolamine buffer at pH 2.5, an applied voltage of 15 kV, and a temperature of 25°C. The CE strategy implemented in the separation starts by screening prior to the optimization stage in which an experimental design is applied. The design of experiment (DOE) was based on a full factorial design of the crucial two factors (pH and %CD) at three levels, to make a total of nine (32) experiments with high, intermediate, and low values for both factors. Evaluation of the proposed strategy pointed out that best resolution was obtained at pH 2.5 for five racemates using low percentages of HS‐γ‐CD, while SBE‐β‐CD was the most successful chiral selector offering acceptable resolution for all the six racemates, with the best separation at low pH values and at higher %CD within 10‐min runtime. Regression study showed that the linear model shows a significant lack of fit for all chiral selectors, anticipating that higher orders of the factors are most likely to be present in the equation with possible interactions. 相似文献
169.
A validation study for six genomic regions previously identified by a genome‐wide association study for somatic cell score was conducted with data of clinical mastitis in German Holstein cattle. Out of 10 tested SNPs, five on chromosomes 6, 13 and 19 were significantly associated with clinical mastitis (P < 0.05). Three SNPs on chromosomes 6 and 19 had the same direction of effect as those previously reported in the initial genome‐wide association study for somatic cell score. The other two SNPs on chromosome 13 had opposite effects. As well as validating associations within known QTL from previous studies, e.g. chromosomes 6 and 19, novel loci on chromosome 13 were confirmed. Promising candidate genes are, for example: deoxycytidine kinase, immunoglobulin J chain, vitamin D binding protein, forkhead box K2, sodium/hydrogen exchanger 8 and cytoplasmic nuclear factor of activated T‐cells 2. Our confirmation study provides additional evidence for the functional role of the linked genomic regions to immune response. This information can be used as a basis for further functional studies for those potential genes. 相似文献
170.
Loubna Abdel Hadi Viviana Anelli Laura Guarnaccia Stefania Navone Matteo Beretta Francesco Moccia Cristina Tringali Vasile Urechie Rolando Campanella Giovanni Marfia Laura Riboni 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(10):1179-1192
Glioblastoma is one of the most malignant, angiogenic, and incurable tumors in humans. The aberrant communication between glioblastoma cells and tumor microenvironment represents one of the major factors regulating glioblastoma malignancy and angiogenic properties. Emerging evidence implicates sphingosine-1-phosphate signaling in the pathobiology of glioblastoma and angiogenesis, but its role in glioblastoma-endothelial crosstalk remains largely unknown. In this study, we sought to determine whether the crosstalk between glioblastoma cells and brain endothelial cells regulates sphingosine-1-phosphate signaling in the tumor microenvironment. Using human glioblastoma and brain endothelial cell lines, as well as primary brain endothelial cells derived from human glioblastoma, we report that glioblastoma-co-culture promotes the expression, activity, and plasma membrane enrichment of sphingosine kinase 2 in brain endothelial cells, leading to increased cellular level of sphingosine-1-phosphate, and significant potentiation of its secretion. In turn, extracellular sphingosine-1-phosphate stimulates glioblastoma cell proliferation, and brain endothelial cells migration and angiogenesis. We also show that, after co-culture, glioblastoma cells exhibit enhanced expression of S1P1 and S1P3, the sphingosine-1-phosphate receptors that are of paramount importance for cell growth and invasivity. Collectively, our results envision glioblastoma-endothelial crosstalk as a multi-compartmental strategy to enforce pro-tumoral sphingosine-1-phosphate signaling in the glioblastoma microenvironment. 相似文献