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Farouk Semcheddine Nida El Islem Guissi XueYin Liu ZuoMin Wu Bo Wang 《AAPS PharmSciTech》2015,16(3):704-715
The aims of this study were to enhance the solubility and dissolution rate of nimodipine (ND) by preparing the inclusion complexes of ND with sulfobutylether-b-cyclodextrin (SBE-β-CD) and 2-hydroxypropyl-b-cyclodextrin (HP-β-CD) and to study the effect of the preparation method on the in vitro dissolution profile in different media (0.1 N HCl pH 1.2, phosphate buffer pH 7.4, and distilled water). Thus, the inclusion complexes were prepared by kneading, coprecipitation, and freeze-drying methods. Phase solubility studies were conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were investigated with differential scanning calorimetry (DSC), X-ray diffractometry (X-RD), and Fourier transform infrared spectroscopy (FT-IR). Stable complexes of ND/SBE-β-CD and ND/HP-β-CD were formed in distilled water in a 1:1 stoichiometric inclusion complex as indicated by an AL-type diagram. The apparent stability constants (Ks) were 1334.4 and 464.1 M−1 for ND/SBE-β-CD and ND/HP-β-CD, respectively. The water-solubility of ND was significantly increased in an average of 22- and 8-fold for SBE-β-CD and HP-β-CD, respectively. DSC results showed the formation of true inclusion complexes between the drug and both SBE-β-CD and HP-β-CD prepared by the kneading method. In contrast, crystalline drug was detectable in all other products. The dissolution studies showed that all the products exhibited higher dissolution rate than those of the physical mixtures and ND alone, in all mediums. However, the kneading complexes displayed the maximum dissolution rate in comparison with drug and other complexes, confirming the influence of the preparation method on the physicochemical properties of the products. 相似文献
66.
Nadeem N Woodside JV Kelly S Allister R Young IS McEneny J 《The Journal of nutritional biochemistry》2012,23(7):845-851
BackgroundVitamin E and its derivatives, namely, the tocopherols, are known antioxidants, and numerous clinical trials have investigated their role in preventing cardiovascular disease; however, evidence to date remains inconclusive. Much of the in vitro research has focused on tocopherol's effects during low-density lipoprotein (LDL) oxidation, with little attention being paid to very LDL (VLDL) and high-density lipoprotein (HDL). Also, it is now becoming apparent that γ-tocopherol may potentially be more beneficial in relation to cardiovascular health.ObjectivesDo α- and γ-tocopherols become incorporated into VLDL, LDL and HDL and influence their oxidation potential in an in vitro and ex vivo situation?DesignFollowing (i) an in vitro investigation, where plasma was preincubated with increasing concentrations of either α- or γ-tocopherol and (ii) an in vivo 4-week placebo-controlled intervention with α- or γ-tocopherol. Tocopherol incorporation into VLDL, LDL and HDL was measured via high-pressure liquid chromatography, followed by an assessment of their oxidation potential by monitoring conjugated diene formation.ResultsIn vitro: Both tocopherols became incorporated into VLDL, LDL and HDL, which protected VLDL and LDL against oxidation. However and surprisingly, the incorporation into HDL demonstrated pro-oxidant properties. Ex vivo: Both tocopherols were incorporated into all three lipoproteins, protecting VLDL and LDL against oxidation; however, they enhanced the oxidation of HDL.ConclusionsThese results suggest that α- and γ-tocopherols display conflicting oxidant activities dependent on the lipoprotein being oxidized. Their pro-oxidant activity toward HDL may go some way to explain why supplementation studies with vitamin E have not been able to display cardioprotective effects. 相似文献
67.
Akhter SA D'Souza KM Petrashevskaya NN Mialet-Perez J Liggett SB 《American journal of physiology. Heart and circulatory physiology》2006,290(4):H1427-H1432
Association studies suggest beta(1)-adrenergic receptor (beta(1)-AR) polymorphisms are disease modifiers in heart failure. The Arg389 variant has increased coupling to G(s) in transfected cells and evokes enhanced ventricular function in transgenic mice. Here, we assessed the differential effects of the human Gly389 and Arg389 beta(1)-AR polymorphisms on myocardial recovery after ischemic injury. Function was studied in transgenic mice with cardiac-specific expression of either human Gly389 or Arg389 beta(1)-AR at baseline and after 20 min of ex vivo ischemia and reperfusion (I/R). In 3-mo-old mice of either genotype, there was poor recovery after I/R (approximately 38% vs. approximately 68% for nontransgenic). Paradoxically, at 6 mo of age, functional recovery remained severely depressed in Gly389 hearts (approximately 32%) but was similar to nontransgenic for Arg389 hearts (approximately 60%). In Arg389 hearts, agonist-promoted adenylyl cyclase activities were depressed by approximately 35% at 6 mo of age, and G protein-coupled receptor kinase (GRK) activity was increased by approximately twofold compared with Gly389. Furthermore, I/R evoked an approximately threefold increase in ERK2 phosphorylation in Arg389 but an approximately twofold decrease in Gly389 hearts. Individually, these changes have been shown to mitigate I/R injury; thus the Arg389-beta(1)-AR uniquely evokes specialized pathways that act to protect against I/R injury. The improved recovery of function after I/R in Arg389 hearts relative to Gly389 appears to be due to an adaptive multimechanism program with allele-specific alterations in receptor signaling, GRK activity, and ERK2. Thus genetic variation of the human beta(1)-AR may play a role in cardiac functional recovery after ischemic injury. 相似文献
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Khalid M. Khan Naheed Fatima Maimona Rasheed Saima Jalil Nida Ambreen Shahnaz Perveen M. Iqbal Choudhary 《Bioorganic & medicinal chemistry》2009,17(22):7816-7822
A series of 1,3,4-oxadiazole-2 (3H)-thiones and 1,3,4-thiadiazole-2 (3H)-thiones were synthesized and evaluated for their inhibitory activities against the two nucleotide pyrophosphatase phosphodiesterase 1 enzymes. Dixon, as well as Lineweaver–Burk plots, and their secondary replots have indicated that the inhibition was of pure non-competitive type, against both snake venom and pure human recombinant enzymes as the Vmax values decreases without affecting the Km values. 5-[4-(t-Butyldimethylsilyloxy)-phenyl]-1,3,4-thiadiazole-2 (3H)-thione (17) and [4-(t-butyldimethylsilyloxy)-phenyl]-1,3,4-oxadiazole-2 (3H)-thione (1) were found to be the most active compounds with IC50 values 66.47 and 368 μM, respectively. The Ki values were 100 μM and 360 μM against the snake venom and human recombinant NPP1 enzyme, respectively. Most active compounds were found to be non-toxic in neutrophil viability assay. 相似文献
69.
Venkata S.P. Bitra Alvin R. Womac C. Igathinathane Petre I. Miu Yuechuan T. Yang David R. Smith Nehru Chevanan Shahab Sokhansanj 《Bioresource technology》2009,100(24):6578-6585
Lengthy straw/stalk of biomass may not be directly fed into grinders such as hammer mills and disc refiners. Hence, biomass needs to be preprocessed using coarse grinders like a knife mill to allow for efficient feeding in refiner mills without bridging and choking. Size reduction mechanical energy was directly measured for switchgrass (Panicum virgatum L.), wheat straw (Triticum aestivum L.), and corn stover (Zea mays L.) in an instrumented knife mill. Direct power inputs were determined for different knife mill screen openings from 12.7 to 50.8 mm, rotor speeds between 250 and 500 rpm, and mass feed rates from 1 to 11 kg/min. Overall accuracy of power measurement was calculated to be ±0.003 kW. Total specific energy (kWh/Mg) was defined as size reduction energy to operate mill with biomass. Effective specific energy was defined as the energy that can be assumed to reach the biomass. The difference is parasitic or no-load energy of mill. Total specific energy for switchgrass, wheat straw, and corn stover chopping increased with knife mill speed, whereas, effective specific energy decreased marginally for switchgrass and increased for wheat straw and corn stover. Total and effective specific energy decreased with an increase in screen size for all the crops studied. Total specific energy decreased with increase in mass feed rate, but effective specific energy increased for switchgrass and wheat straw, and decreased for corn stover at increased feed rate. For knife mill screen size of 25.4 mm and optimum speed of 250 rpm, optimum feed rates were 7.6, 5.8, and 4.5 kg/min for switchgrass, wheat straw, and corn stover, respectively, and the corresponding total specific energies were 7.57, 10.53, and 8.87 kWh/Mg and effective specific energies were 1.27, 1.50, and 0.24 kWh/Mg for switchgrass, wheat straw, and corn stover, respectively. Energy utilization ratios were calculated as 16.8%, 14.3%, and 2.8% for switchgrass, wheat straw, and corn stover, respectively. These data will be useful for preparing the feed material for subsequent fine grinding operations and designing new mills. 相似文献
70.
Tasneem Gul Kazi Ghulam Abbas Kandhro Hassan Imran Afridi Naveed Kazi Jameel Ahmed Baig Mohammad Balal Arain Abdul Qadir Shah Nasreen Syed Sham Kumar Nida Fatima Kolachi Sumaira Khan 《Biological trace element research》2010,134(3):265-279
In many developing countries, men and women are at high risk of goiter and iron deficiency. The aim of the recent study is to assess the interaction of (Cu), with iron (Fe), iodine/iodide (I), and thyroid hormones in goitrous patients. Sixty goitrous male (GMPs) and 72 female patients (GFPs) were evaluated for the Cu, Fe, I, and thyroid hormones status in biological samples (serum and urine), and compared to non-goitrous subjects of both genders (M?=?106, F?=?120). The biological samples were analyzed for Cu and Fe concentration using atomic absorption spectrometer, while I was measured by the potentiometric method, prior to microwave-assisted acid digestion (MD). Quality control for the method was established with certified samples. Significantly higher mean values of Cu in serum, and urine samples of GMPs and GFPs, while lower value of Fe and I were observed as compared to control subjects (p?<?0.015), respectively. The mean values of free triiodothyronine (FT3) and free thyroxin (FT4) were found to be lower in goitrous patients of both genders than in the age-matched healthy controls (p?<?0.006 and 0.002), respectively, in contrast high mean values of thyroid-stimulating hormone (TSH) were detected in patients (p?<?0.009), as compared to non-goitrous subjects. It was observed that the deficiencies of Fe, I, and thyroid hormone in goitrous patients could be influenced by efficiency of Cu. 相似文献