In this paper, both maghemite (γ-Fe2O3) and titanium oxide (TiO2) nanoparticles were synthesized and mixed in various ratios and embedded in PVA and alginate beads. Batch sorption experiments were applied for removal of barium ions from aqueous solution under sunlight using the beads. The process has been investigated as a function of pH, contact time, temperature, initial barium ion concentration and TiO2:γ-Fe2O3 ratios (1:10, 1:60 and 1). The recycling attributes of these beads were also considered. Furthermore, the results revealed that 99% of the Ba(II) was eliminated in 150min at pH 8 under sunlight. Also, the maghemite and titania PVA-alginate beads can be readily isolated from the aqueous solution after the process and reused for at least 7 times without significant losses of their initial properties. The reduction of Ba(II) with maghemite and titania PVA-alginate beads fitted the pseudo first order and second order Langmuir-Hinshelwood (L-H) kinetic model.
Imatinib mesylate is an antineoplastic agent which has high absorption in the upper part of the gastrointestinal tract (GIT). Conventional imatinib mesylate (Gleevec) tablets produce rapid and relatively high peak blood levels and requires frequent administration to keep the plasma drug level at an effective range. This might cause side effects, reduced effectiveness and poor therapeutic management. Therefore, floating sustained-release Imatinib tablets were developed to allow the tablets to be released in the upper part of the GIT and overcome the inadequacy of conventional tablets.
The electrochemical oxidation of caffeine, a widely over-the-counter stimulant drug, has been investigated in effluent wastewater and deionized water (DIW) using graphite-poly vinyl chloride (PVC) composite electrode as anode. Effects of initial concentration of caffeine, chloride ion (Cl(-)) loading, presence of hydrogen peroxide (H2O2), sample volume, type of sample and applied voltage were determined to test and to validate a kinetic model for the oxidation of caffeine by the electrochemical oxidation process. The results revealed that the electrochemical oxidation rates of caffeine followed pseudo first-order kinetics, with rate constant values ranged from 0.006 to 0.23 min(-1) depending on the operating parameters. The removal efficiency of caffeine increases with applied voltage very significantly, suggesting a very important role of mediated oxidation process. However, the consumption energy was considered during electrochemical oxidation process. In chloride media, removal of caffeine is faster and more efficiently, although occurrence of more intermediates takes place. The study found that the adding H2O2 to the NaCl solution will inhibit slightly the electrochemical oxidation rate in comparison with only NaCl in solution. Liquid chromatography-time of flight-mass spectrometry (LC-TOF-MS) technique was applied to the identification of the by-products generated during electrochemical oxidation, which allowed to construct the proposed structure of by-products.
Twelve edible plant extracts rich in polyphenols were screened for their potential to inhibit oxidation of low-density lipoprotein (LDL) in vitro and to modulate LDL receptor (LDLr) activity in cultured HepG2 cells. The antioxidant activity (inhibition of LDL oxidation) was determined by measuring the formation of conjugated dienes (lag time) and thiobarbituric acid reagent substances (TBARS). Betel leaf (94%), cashew shoot (63%), Japanese mint (52%), semambu leaf (50%), palm frond (41%), sweet potato shoot, chilli fruit, papaya shoot, roselle calyx, and maman showed significantly increased lag time (>55 min, P < 0.05) and inhibition of TBARS formation (P < 0.05) compared to control. LDLr was significantly up-regulated (P < 0.05) by Japanese mint (67%), semambu (51%), cashew (50%), and noni (49%). Except for noni and betel leaf, most plant extracts studied demonstrated a positive association between antioxidant activity and the ability to up-regulate LDL receptor. Findings suggest that reported protective actions of plant polyphenols on lipoprotein metabolism might be exerted at different biochemical mechanisms.
1. Glucocorticosteroid may relieve bronchospasm by mediating changes in the muscarinic receptor concentration and/or its affinity. 2. Cholinergic muscarinic receptors were determined by using Scatchard's plots from radioligand binding assays of 0.13-3.2 nM [3H]quinuclidinyl benzylate binding to the membrane fraction of bronchial smooth muscle (BSM). 3. The concentration of muscarinic receptor in BSM of normal rat was 57 +/- 3 fmol mg protein and the dissociation constant was 0.07 +/- 0.02 nM. Dexamethasone and corticosterone reduced muscarinic receptor concentration to 50-60% of basal with no changes in receptor affinity. No changes were found in rat treated with deoxycorticosterone. 4. These findings suggest that glucocorticoids but not mineralocorticoid relieve bronchospasm at least partly by reducing the cholinergic hypersensitivity.
Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss-of-function Nav 1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain-of-function Nav 1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life-threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low-grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.
This study aimed to express two major drug-metabolizing human hepatic cytochromes P450 (CYPs), CYP2D6 and CYP3A4, together with NADPH-cytochrome P450 oxidoreductase (OxR) in Escherichia coli and to evaluate their catalytic activities. Full length cDNA clones of both isoforms in which the N-terminus was modified to incorporate bovine CYP17α sequence were inserted into a pCWori(+) vector. The modified CYP cDNAs were subsequently expressed individually, each together with OxR by means of separate, compatible plasmids with different antibiotic selection markers. The expressed proteins were evaluated by immunoblotting and reduced CO difference spectral scanning. Enzyme activities were examined using high performance liquid chromatography (HPLC) assays with probe substrates dextromethorphan and testosterone for CYP2D6 and CYP3A4, respectively. Results from immunoblotting demonstrated the presence of both CYP proteins in bacterial membranes and reduced CO difference spectra of the cell preparations exhibited the characteristic absorbance peak at 450 nm. Co-expressed OxR also demonstrated an activity level comparable to literature values. Kinetic parameters, K(m) and V(max) values determined from the HPLC assays also agreed well with literature values. As a conclusion, the procedures described in this study provide a relatively convenient and reliable means of producing catalytically active CYP isoforms suitable for drug metabolism and interaction studies.
Novel bi-heterocyclic benzamides were synthesized by sequentially converting 4-(1H-indol-3-yl)butanoic acid (1) into ethyl 4-(1H-indol-3-yl)butanoate (2), 4-(1H-indol-3-yl)butanohydrazide (3), and a nucleophilic 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazole-2-thiol (4). In a parallel series of reactions, various electrophiles were synthesized by reacting substituted anilines (5a-k) with 4-(chloromethyl)benzoylchloride (6) to afford 4-(chloromethyl)-N-(substituted-phenyl)benzamides (7a-k). Finally, the nucleophilic substitution reaction of 4 was carried out with newly synthesized electrophiles, 7a-k, to acquire the targeted bi-heterocyclic benzamides, 8a-k. The structural confirmation of all the synthesized compounds was done by IR, 1 H NMR, 13 C NMR, EI-MS, and CHN analysis data. The inhibitory effects of these bi-heterocyclic benzamides (8a-k) were evaluated against alkaline phosphatase, and all these molecules were identified as potent inhibitors relative to the standard used. The kinetics mechanism was ascribed by evaluating the Lineweaver-Burk plots, which revealed that compound 8b inhibited alkaline phosphatase non-competitively to form an enzyme-inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 1.15 μM. The computational study was in full agreement with the experimental records and these ligands exhibited good binding energy values. These molecules also exhibited mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds to render normal calcification of bones and teeth.
Phosphoric acid impregnated activated carbon from date pits (DPAC) was prepared through single step activation. Prepared DPAC was studied for its structural, elemental, chemical, surface and crystal nature. Adsorption ability of the DPAC was assessed through divalent lead ions separation studies. Effect of adsorbent dosage, contact time, pH, operating temperature and initial feed concentration on lead removal by DPAC was studied. Maximum Pb(II) adsorption capacity of 101.35 mg/g was attained for a contact time of 30 min and pH of 6 at 30°C. Increase in initial feed concentration enhanced the adsorption ability of DPAC and the rise in adsorbent dosage resulted in improved Pb(II) removal efficiency. Thermodynamic studies revealed that the lead adsorption on DPAC was exothermic and instantaneous in nature. Kinetic and equilibrium studies confirmed the suitability of pseudo-second order and Langmuir isotherm for divalent lead ions binding on DPAC. Reusability studies showed that HCl was the effective regeneration medium and the DPAC could be reused for a maximum of 4 times with slight reduction in Pb(II) removal efficiency (<10%). Results indicated the promising use of date pits biomass as a low cost and efficient starting material to prepare activated carbon for divalent lead ions removal.
Matched MeSH terms: Ions/pharmacokinetics; Kinetics; Lead/pharmacokinetics; Water Pollutants, Chemical/pharmacokinetics
A thrombin-like enzyme (termed albolabrase) was isolated in purified form from the venom of Cryptelytrops albolabris (white-lipped tree viper) using high performance anion ion exchange and gel filtration chromatography. The molecular mass of albolabrase was 33.7 kDa as determined by SDS-PAGE and 35.8 kDa as determined by Superose gel filtration chromatography. The N-terminal sequence was determined to be VVGGDECNINE which is homologous to many snake venom thrombin-like enzymes. Albolabrase exhibits both arginine ester hydrolase and arginine amidase activities and the enzyme is fastidious towards tripeptide chromogenic anilide substrates. The fibrinogen clotting activity was optimum at 3mg/mL bovine fibrinogen, and showed distinct species differences in the following decreasing order: bovine fibrinogen>dog fibrinogen≈human fibrinogen>goat fibrinogen. The enzyme failed to clot both rabbit and cat fibrinogens. Reversed-phase HPLC analysis on the breakdown products of fibrinogenolytic action of albolabrase indicated that the enzyme belongs to the AB class of snake venom thrombin-like enzyme. In the indirect ELISA, IgG anti-albolabrase reacted extensively with most crotalid venoms, except with Tropidolaemus wagleri and Calloselasma rhodostoma venoms. The double sandwich ELISA, however, showed that anti-albolabrase reacted strongly only with venoms from the Trimeresurus complex, and that the results support the proposed new taxonomy changes concerning the Trimeresurus complex.
The present research was designed for the selective synthesis of novel bi-heterocyclic acetamides, 9a-n, and their tyrosinase inhibition to overwhelm the problem of melanogenesis. The structures of newly synthesized compounds were confirmed by spectral techniques such as 1H NMR, 13C NMR, and EI-MS along with elemental analysis. The inhibitory effects of these bi-heterocyclic acetamides (9a-n) were evaluated against tyrosinase and all these molecules were recognized as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which explored that compound, 9h, inhibited tyrosinase competitively by forming an enzyme-inhibitor complex. The inhibition constants Ki calculated from Dixon plots for this compound was 0.0027 µM. The computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal/mol). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules can be pondered as nontoxic medicinal scaffolds for skin pigmentation and related disorders.
Rice husk is a base adsorbent for pollutant removal. It is a cost-effective material and a renewable resource. This study provides the physicochemical characterization of chemically and thermally treated rice husk adsorbents for phenol removal from aqueous solutions. We revealed new functional groups on rice husk adsorbents by Fourier transform infrared spectroscopy, and observed major changes in the pore structure (from macro-mesopores to micro-mesopores) of the developed rice husk adsorbents using scanning electron microscopy. Additionally, we studied their surface area and pore size distribution, and found a greater enhancement of the morphological structure of the thermally treated rice husk compared with that chemically treated. Thermally treated adsorbents presented a higher surface area (24-201 m2.g-1) than those chemically treated (3.2 m2.g-1). The thermal and chemical modifications of rice husk resulted in phenol removal efficiencies of 36%-64% and 28%, respectively. Thus, we recommend using thermally treated rice husk as a promising adsorbent for phenol removal from aqueous solutions.
Gellan gum based floating beads containing clarithromycin (FBC) were prepared by iontotropic gelation method for stomach-specific drug delivery against Helicobacter pylori. The scanning electron microscope photograph indicated that prepared beads were spherical in shape with rough outer surface. Formulation variables such as concentrations of gellan, calcium carbonate and drug loading influenced the in vitro drug release characteristics of prepared beads. In vitro release rate of clarithromycin was corrected using first order degradation rate constant which is degraded significantly during the release study in simulated gastric fluid pH 2.0. Further, the absence of interactions between drug and polymer was confirmed by differential scanning calorimetry analysis. Kinetic treatment of the in vitro drug release data with different kinetic equations revealed matrix diffusion mechanism. Prepared beads showed good anti-microbial activity against isolated H. pylori strain. The prepared beads have shown good in vivo floating efficiency in rabbit stomach. The stability studies of beads did not show any significant changes after storage of beads at 40 degrees C/75% relative humidity for 6 months. The preliminary results from this study suggest that floating beads of gellan can be used to incorporate antibiotics like clarithromycin and may be effective when administered locally in the stomach against H. pylori.
NADP(+)-dependent geraniol dehydrogenase (EC 1.1.1.183) is an enzyme that catalyzes the oxidation of geraniol to geranial. Stable, highly active cell-free extract was obtained from Polygonum minus leaves using polyvinylpolypyrrolidone, Amberlite XAD-4, glycerol, 2-mercaptoethanol, thiourea, and phenylmethylsulfonylfluoride in tricine-NaOH buffer (pH 7.5). The enzyme preparation was separated into two activity peaks, geraniol-DH I and II, by DEAE-Toyopearl 650M column chromatography at pH 7.5. Both isoenzymes were purified to homogeneity in three chromatographic steps. The geraniol-DH isoenzymes were similar in molecular mass, optimal temperature, and pH, but the isoelectric point, substrate specificity, and kinetic parameters were different. The K(m) values for geraniol of geraniol-DH I and II appeared to be 0.4 mM and 0.185 mM respectively. P. minus geraniol-DHs are unusual among geraniol-DHs in view of their thermal stability and optimal temperatures, and also their high specificity for allylic alcohols and NADP(+).
Stem cells isolated from dental pulp possess the capacity for self-renewal and the potential for multi-lineage differentiation. However, dental pulp stem cells have different characteristics in terms of their culture conditions. The success of stem cells culture is governed by its micro-environmental niche. Therefore, we studied the effects of culture niche on long-term expansion of dental pulp stem cells in terms of cell morphology, growth kinetics, senescence pattern, cell surface marker expression differentiation capacity, and seeding plating density of dental pulp stem cells in four different, widely used media composition Among the various basal media tested, α-minimum essential media and knock out-minimum essential media supplemented with 10% fetal bovine serum were found to be the most optimal media composition in preserving the phenotypic characteristics and differentiation potential for prolonged periods as compared with DMEM-F12 and DMEM-LG. Plating density has been shown to affect overall yield. As a conclusion, the adoption of an appropriate culture system significantly improved cell yield, thus enabling the attainment of sufficient yields for therapeutic applications economizing in terms of cost of production and minimizing seeding cell density for maximum yield.
Oil palm trunk (OPT) is one of the most promising lignocellulosic bioresources. To develop effective biodegradation, thermophilic, anaerobic microorganisms were screened from bovine manure compost using fibrillated OPT (f-OPT) pretreated by wet disk milling as the substrate. One thermophilic, anaerobic bacterium, strain CL-2, whose 16S rDNA gene has 98.6% sequence identity with that of Caldicoprobacter faecale DSM 20678T, exhibited high degradation activity (32.7% reduction in total dry solids of f-OPT). Strain CL-2 did not use cellulose as a carbon source, but used hemicelluloses such as xylan, arabinoxylan, starch and pectin at 70 °C. Phylogenetic and morphologic analyses and the polysaccharide use suggest that CL-2 may be classified as a novel species of Caldicoprobacter, named Caldicoprobacter sp. CL-2. To characterize enzymatic activities of CL-2, extracellular enzymes were prepared from culture broth using beechwood xylan as the carbon source. The extracellular enzymes showed high xylanase activity, but low cellulase activity, suggesting that f-OPT degradation may depend on xylanase activity. To understand the xylanase system of CL-2, a major xylanase was cloned and characterized. The xylanase (CalXyn11A) had a modular structure consisting of a glycoside hydrolase (GH) family-11 domain and a family 36 carbohydrate-binding module. CalXyn11A did not show f-OPT degradation activity, but a strong synergistic effect was observed when CalXyn11A was added to the extracellular enzyme preparation. These results indicate that, rather than working alone, CalXyn11A has an important role in enhancing total lignocellulose degradation activity by cooperation with other GHs.
The objective of this study was to screen and identify α-amylase inhibitor peptides from Pinto bean. Five Pinto bean bioactive peptides were successfully identified: PPHMLP (P1), PLPWGAGF (P3), PPHMGGP (P6), PLPLHMLP (P7) and LSSLEMGSLGALFVCM (P9). Based on ELISA results, their promising optical density values were 1.27; 3.71, 1.67, 3.20 and 1.03, respectively, which indicated the binding interaction between the peptide and α-amylase occurred. The highest inhibitory activity (66.72%) of the chemically synthesized peptide was shown in SyP9 followed by SyP1 (48.86%), SyP3 (31.17%), SyP7 (27.88%) and SyP6 (23.96%). The IC50 values were 1.97, 8.96, 14.63, 18.45 and 20.56mgml(-1), respectively. Structure activity relationship study revealed that α-amylase was inhibited due to its residues of Ala230, Asp229, Asp326, Tyr54, Met195, Leu194 and His233 were bound. On the other hand, the residues of PBBP (i.e. histidine, proline and methionine) were found to have the highest potency in the binding interaction.
Curdlan (CN)-doped montmorillonite/poly(N-isopropylacrylamide-co-N,N'-methylene-bis-acrylamide) [CN/MT/P(NIPA-co-MBA)] smart nanocomposites (NCs) were developed for efficient erlotinib HCl (ERL) delivery to lung cancer cells. The placebo NCs demonstrated excellent biodegradability, pH/thermo-responsive swelling profiles and declined molar mass (M¯c) between the crosslinks with increasing temperature. The XRD, FTIR, DSC, TGA, and SEM analyses revealed the architectural chemistry of these NC scaffolds. The NCs loaded with ERL (F-1-F-3) displayed acceptable diameter (734-1120 nm) and zeta potential (+1.16 to -11.17 mV), outstanding drug entrapping capability (DEE, 78-99%) and sustained biphasic ERL elution patterns (Q8h, 53-91%). The ERL release kinetics of the optimal matrices (F-3) obeyed Higuchi model and their transport occurred through anomalous diffusion. The mucin adsorption behaviour of these matrices followed Freudlich isotherms. As compared to pure ERL, the formulation (F-3) displayed an improved anti-proliferative potential and induced apoptosis more effectively on A549 cells. Thus, the CN-doped smart NCs could be utilized as promising drug-cargoes for lung cancer therapy.
Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC50 = 23.08 ± 0.03 µM), (IC50 = 26.08 ± 0.43 µM), 5 (IC50 = 24.57 ± 0.07 µM), (IC50 = 27.57 ± 0.07 µM), 6 (IC50 = 24.94 ± 0.12 µM), (IC50 = 27.13 ± 0.08 µM), 16 (IC50 = 27.57 ± 0.07 µM), (IC50 = 29.13 ± 0.18 µM), and 28 (IC50 = 26.94 ± 0.12 µM) (IC50 = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.