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1.
The metal complexes and salts of amine carboxyboranes were shown to be potent anti-inflammatory agents in rodents at 8 mg kg?1. They were effective in blocking induced edema, pleurisy and endotoxic shock while blocking both local and central pain processes. The ability of the agents to function as anti-inflammatory agents is multi-fold. First, lysosomal enzymes of specific cells, e.g. macrophages, were inhibited with IC50 values in the range of 10?6 M . Collagenase I and II activities were inhibited with IC50 values approximately equal to 10?4 M . The anti-inflammatory activity of these agents at the molecular levels appears to be due to inhibition of the release of TNFα and Il-1 from macrophages which indirectly control chemotaxic migration of white blood cells as indicated by the suppression of PMN and macrophage invasion into sponges implanted subcutaneously (SC) in mice. Furthermore, in these invading cells, the agents' blockage of TNFα and Il-1 or Il-2 release down-regulates prostaglandin and leukotriene enzymatic synthetic rates and, consequently, their release, resulting in a reduction of the inflammation process.  相似文献   

2.
By using the van’t Hoff and Gibbs equations, solubility data of ibuprofen (IBP) and naproxen (NAP) determined at several temperatures in propylene glycol (PG) + water (W) cosolvent mixtures were used to evaluate the Gibbs energies, enthalpies, and entropies of solution, mixing and solvation. The solubilities are greater in pure PG and lower in W in both cases at all studied temperatures. These results clearly show that a cosolvent effect is present in these systems. The solvation of these drugs was greater in W compared to PG, and it was lower in the cosolvent mixtures compared with the pure solvents. By means of an enthalpy-entropy compensation analysis, non-linear ΔH solno versus ΔG solno compensation plots were obtained, with negative and positive slopes if all of the composition intervals are considered. Accordingly, it follows that at low PG solvent fractions the dominant factor for the solubility of IBP and NAP in this cosolvent system is the entropy, probably due to loosening of the water structure caused by the addition of the cosolvent.  相似文献   

3.
Propyl gallate [3,4,5-trihydroxybenzoic acid propyl ester; PG] exhibits an anti-growth effect in various cells. In this study, the anti-apoptotic effects of various caspase inhibitors were evaluated in PG-treated Calu-6 and A549 lung cancer cells in relation to reactive oxygen species (ROS) and glutathione (GSH) levels. Treatment with 800 μM PG inhibited the proliferation and induced the cell death of both Calu-6 and A549 cells at 24 h. Each inhibitor of pan-caspase, caspase-3, caspase-8, and caspase-9 reduced the number of dead and sub-G1 cells in both PG-treated cells at 24 h. PG increased ROS levels, including O2∙−, in both lung cancer cell lines at 24 h. Generally, caspase inhibitors appeared to decrease ROS levels in PG-treated lung cancer cells at 24 h and somewhat reduced O2∙− levels. PG augmented the number of GSH-depleted Calu-6 and A549 cells at 24 h. Caspase inhibitors did not affect the level of GSH depletion in PG-treated A549 cells but differently and partially altered the depletion level in PG-treated Calu-6 cells. In conclusion, PG exhibits an anti-proliferative effect in Calu-6 and A549 lung cancer cells and induced their cell death. PG-induced lung cancer death was accompanied by increases in ROS levels and GSH depletion. Therefore, the anti-apoptotic effects of caspase inhibitors were, at least in part, related to changes in ROS and GSH levels.  相似文献   

4.
Extraction behavior of Th(IV) and U(VI) has been investigated with bis(2-ethylhexyl) phosphinic acid (PIA-8) and bis(2-ethylhexyl) phosphoric acid (HDEHP) from nitric acid media in toluene. The optimum conditions for extraction of these metals have been established by studying various parameters like acid concentration, pH, reagent concentration, diluents and shaking time. The extraction of Th(IV) was found to be quantitative with 0.3-2.5M HNO3 by 2.5.10-2M HDEHP and in the pH range 0.1-2.5 with 2.3.10-2M PIA-8 in toluene. U(VI) was completely extracted in the acidic range of 0.1-2.0M HNO3 with 2.2.10-2M HDEHP and in the pH range of 1.0-3.0 with 2.0.10-2M PIA-8 in toluene. The probable extracted species have been ascertained by log D-log c plot as UO2 R2 .2HR with both the reagents and Th (NO3)2R2 .2HR with PIA-8 and Th (NO3)3R.3HR with HDEHP, respectively. Temperature dependence of the extraction equilibrium is examined by the temperature variation method. Separation of U(VI) and Th(IV) was also carried out from commonly associated metals.  相似文献   

5.
Extraction of U(VI), Zr(IV) and Th(IV) has been investigated from perchlorate media using 2-ethylhexyl phosphonic acid mono-2-ethylhexyl ester (PC-88A) dissolved in toluene. The extraction of U(VI), Zr(IV) and Th(IV) was found to be quantitative in the pH range 1.6 to 3.2, 2.0 to 4.7 and 2.3 to 3.8, respectively, with 3.0.10-3, 5.6.10-4 and 1.0.10-2M PC-88A dissolved in toluene. U(VI) was stripped with 4.0M HCl, Zr(IV) with 2.5M NaF and Th(IV) with 8.0M HCl from the metal loaded organic phase containing PC-88A dissolved in toluene. The probable extracted species have been ascertained by plotting log D vs. log [HR] as UO2R2 .2HR, ZrR4 .2HR and ThR4 .4HR, respectively. U(VI) was separated from Zr(IV) and Th(IV) and from other associated metals. This method was proved by the determination of U(VI) in some real samples.  相似文献   

6.
Preparation of a polypyrrole nanofiber (PPyNF) modified pencil graphite (PG) electrode and its usage in the electrochemical DNA biosensors was investigated. The electrodes (PPyNF/PG1 and PPyNF/PG2) were prepared from a solution containing 0.1 M pyrrole, 0.1 M Na2CO3 and 0.1 M LiCIO4 by using potentiostatic and potentiodynamic methods. PPyNF/PG2 electrodes which were prepared by potentiostatic procedure showed higher responses for the oxidation of ds‐DNA than the PPyNF/PG1 electrodes prepared by potentiodynamic methods. Immobilization of the ds‐DNA on PG and PPyNF/PG surfaces was performed at a constant potential, +0.5 V, for 300 s in 0.5 M ABS (pH 4.8) containing 15 μg mL?1 ds‐DNA and 20 mM LiCIO4. The oxidation peak potentials of the ds‐DNA bases, guanine and adenine, were shifted to more cathodic values by using PPyNF/PG electrodes. The oxidation signal of the guanine base of ds‐DNA was decreased in the presence of methylene blue.  相似文献   

7.
Abstract— Protection by acridine orange against ultraviolet light effects in resting cells of E. coli B/r/1, try- was studied with special reference to a possible oxygen effect. Dose-response relationships were described by the function S= 1–(1 - e-kD)n where S is the surviving fraction and D is the u.v. dose in ergs/mm2. For cells suspended in 5 × 10--6M acridine orange (AO) in air, the radiation sensitivity k was reduced from 0.010 (ergs/mm2))-1 in the absence of the dye to 0.0053 (ergs/mm2)-1 in the presence of the dye. Under anoxia at this AO concentration, k was further reduced to 0.0015 (ergs/mm2)-1. The oxygen effect ratio, kO2/kN2, was 3.5 at this concentration of AO. Greater protection was observed in cells suspended in 2 × 10--5M AO, the oxygen effect ratio was unchanged. No oxygen effect was detected in the u.v. response in the absence of the dye. The value of n was reduced from about 12 with no dye to about 5 at dye concentrations of 5 × 10--6M AO or more when oxygen was present. Under anoxia, in the presence of AO, n was further reduced to about 1.3. Atebrin, an efficient u.v. protective agent but an inefficient photodynamic agent, had no oxygen effect for protection against u.v. inactivation. Acridine orange protected against u.v.-induced reversion to tryptophan indepence in E. coli WP2 to about the same extent as it did for inactivation. A similar oxygen effect was observed for both inactivation and mutagenesis.  相似文献   

8.
Tumor-associated macrophages (TAM) are key regulators of the link between inflammation and cancer, and the interplay between TAM and tumor cells represents a promising target of future therapeutic approaches. We investigated the effect of gallic acid (GA) and caffeic acid (CA) as strong antioxidant and anti-inflammatory agents on tumor growth, angiogenesis, macrophage polarization, and oxidative stress on the angiogenic model caused by the intraperitoneal (ip) inoculation of Ehrlich ascites tumor (EAT) cells (2.5 × 106) in Swiss albino mouse. Treatment with GA or CA at a dose of 40 mg/kg and 80 mg/kg ip was started in exponential tumor growth phase on days 5, 7, 9, and 11. On day 13, the ascites volume and the total number and differential count of the cells present in the peritoneal cavity, the functional activity of macrophages, and the antioxidant and anti-angiogenic parameters were determined. The results show that phenolic acids inhibit the processes of angiogenesis and tumor growth, leading to the increased survival of EAT-bearing mice, through the protection of the tumoricidal efficacy of M1 macrophages and inhibition of proangiogenic factors, particularly VEGF, metalloproteinases -2 and -9, and cyclooxygenase-2 activity.  相似文献   

9.
Summary The complexation behavior of Co2+with ortho-silicic acid (o-SA) has been studied as a function of ionic strength (I) from 0.20 to 1.00M (NaClO4) at pH 4.96±0.03 and 25 °C by solvent extraction with bis(2-ethylhexyl) phosphoric acid (HDEHP) as the extractant. The stoichiometry of the extracted species was determined to be Co(DEHP)2(HDEHP)2. Co2+forms a 1:1 complex, CoOSi(OH)3+, as the predominant species witho-SA concentrations of 3.00. 10-4to 4.00. 10-3M. The stability constant (logb1) values for CoOSi(OH)3+complex decrease with the increase in ionic strength. These values were fitted with the extended Debye-Huckel expression to obtain the value of logb1at I=0.00M. The effect of aging time of the o-SA solution on logb1values for CoOSi(OH)3+complex was investigated and compared with those of the UO2OSi(OH)3+complex.  相似文献   

10.
 A selective, sensitive and simple catalytic method is developed for the determination of vanadium in natural and highly polluted waste waters. The method is based on the catalytic effect of VV and/or VIV on the bromate oxidative-coupling reaction of metol with phloroglucinol (PG). The reaction is followed spectrophotometrically by tracing the oxidation product at 464 nm after 10 minutes of mixing the reagents. The optimum reaction conditions are metol (8.0×10−3 M), PG (4.0×10−3 M) and bromate (2×10−2 M) at 35°C and in presence of an activator-b uffer mixture of 5×10−2 M of each of citric and monochloroacetic acids (pH 2.40). Following the recommended procedure, vanadium can be determined with a linear calibration graph up to 8.0 ng mL−1 and a detection limit, based on the 3sb criterion, of 0.1 ng mL−1. Spectrophotometric determination of as little as 1.0 ng mL−1 of VV or VIV in aqueous solutions gave an average recovery of 98% with relative standard deviations of ?1.8% (n = 5). The proposed method was directly applied to the determination of vanadium in Nile river water and highly polluted industrial wastes. Statistical treatments of analytical results could not detect any systematic error and showed the high accuracy and precision of the developed method. Received November 25, 1999. Revision March 10, 2000.  相似文献   

11.
The accumulation of preheated chromium(III)-thiocyanate complexes onto polyurethane foam (PUF) has been studied. The maximum sorption of Cr(III) (7.01.10-5M) is occurred at pH 2 from 1.2M thiocyanate solution in 10 minute agitation time using 7.25 mg/ml PUF. The sorption data have been investigated by Langmuir, Freundlich and Dubinin-Radushkevich (D-R) isotherms. The Freundlich parameters 1/n = 0.31 and of K F = 9.7.10-4 mol.g-1, Langmuir constants M = 7.03.10-5 mol.g-1 and of b = 1.5.105 l.mol-1 and of D-R constants, C m = 1.91.10-4 mol.g-1, affinity coefficient b = -0.0023 mol2.kJ-2 and sorption energy E = 14.7 kJ.mol-1 have been evaluated. Thermodynamic parameters of enthalpy, entropy and Gibbs free energy suggest the endothermic and spontaneous adsorption of Cr(III)-SCN complex onto PUF at higher temperature. The influence of common anions and cations on the accumulation of chromium-thiocyanate on PUF and possible sorption mechanism of [Cr(SCN)4]- species on PUF is discussed.  相似文献   

12.
Histamine at molar concentrations ranging from 10−5 to 10−7 exerted an inhibitory effect upon IL-2 synthesis by peripheral blood mononuclear cells in normal man; two pathways of inhibition are described. The first pathway was found to alter the T4 lymphocytes which, in the system used in this study, synthesized nearly 90 % of the total IL-2 production and had no suppressive activity. This suggests that histamine can act at the level of IL-2-producing cells. The second pathway of inhibition was related to induction of suppressor cells. Peripheral blood lymphocytes pre-incubated for 1 h with histamine 10−5–10−7 M inhibited the IL-2 synthesis of normal autologous lymphocytes in a co-culture system. This activity was radio-resistant (1200 r) and mediated by T8 lymphocytes. These two pathways of inhibition were mediated by the specific interaction of histamine with H1- and H2-receptor-bearing mononuclear cells.  相似文献   

13.
The preconcentration and voltammetric behavior of BiIII on a sodium humate modified carbon paste electrode was studied by means of cyclic voltammetry (CV) and differential pulse stripping voltammetry (DPSV). The proposed measurement involves an initial nonelectrolytic preconcentration step in which BiIII is complexed by the surface modifier in a solution of 0.05 M KNO3-0.0106 M HNO3 (pH 2.0) and a subsequent electrochemical scan step in which the preconcentrated BiIII was reduced and then oxidized promptly in supporting electrolyte of 0.5 M HNO3. The resulting DPSV anodic current was proportional to the concentration of BiIII ion over the range of 4.78 × 10−8–1.44 × 10−5 M. The detection limit was 4.78 × 10−8 M. The proposed method was used to determine bismuth in various samples. Various factors affecting the electrode behavior were also investigated at the same time.  相似文献   

14.
A novel derivative of ibuprofen and salicylaldehyde N′-(4-hydroxybenzylidene)-2-(4-isobutylphenyl) propane hydrazide (HL) was synthesized, followed by its complexation with Cu, Ni, Co, Gd, and Sm. The compounds obtained were characterized by 1HNMR, mass spectrometry, UV-Vis spectroscopy, FT-IR spectroscopy, thermal analysis (DTA and TGA), conductivity measurements, and magnetic susceptibility measurements. The results indicate that the complexes formed were [Cu(L)(H2O)]Cl·2H2O, [Ni(L)2], [Co(L)2]·H2O, [Gd(L)2(H2O)2](NO3)·2H2O and [Sm(L)2(H2O)2](NO3)·2H2O. The surface characteristics of the produced compounds were evaluated by DFT calculations using the MOE environment. The docking was performed against the COX2 targeting protein (PDB code: 5IKT Homo sapiens). The binding energies were −7.52, −9.41, −9.51, −8.09, −10.04, and −8.05 kcal/mol for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, which suggests the enhancement of anti-inflammatory behaviors compared with the binding energy of ibuprofen (−5.38 kcal/mol). The anti-inflammatory properties of the new compounds were assessed in vitro using the western blot analysis method and the enzyme-linked immunosorbent assay (ELISA), consistent with the outcomes obtained from docking. The half-maximal inhibitory concentration (IC50) values are 4.9, 1.7, 3.7, 5.6, 2.9, and 2.3 µM for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, showing that they are more effective inhibitors of COX2 than ibuprofen (IC50 = 31.4 µM). The brain or intestinal estimated permeation method (BOILED-Egg) showed that HL and its Co complex have high gastrointestinal absorption, while only the free ligand has high brain penetration. The binding constants of Co, Cu, and Gd complexes with DNA were recorded as 2.20 × 104, 2.27 × 106, and 4.46 × 103 M−1, respectively, indicating the intercalator behavior of interaction. The newly synthesized ibuprofen derivative and its metal complexes showed greater anti-inflammatory activity than ibuprofen.  相似文献   

15.
The natural compound ravenelin was isolated from the biomass extracts of Exserohilum rostratum fungus, and its antimicrobial, antiplasmodial, and trypanocidal activities were evaluated. Ravenelin was isolated by column chromatography and HPLC and identified by NMR and MS. The susceptibility of Gram-positive and Gram-negative bacteria strains to ravenelin was determined by microbroth dilution assay. Cytotoxicity was evaluated in hepatocarcinoma cells (HepG2) and BALB/c peritoneal macrophages by using MTT. SYBR Green I-based assay was used in the asexual stages of Plasmodium falciparum. Trypanocidal activity was tested against the epimastigote and intracellular amastigote forms of Trypanosoma cruzi. Ravenelin was active against Gram-positive bacteria strains, with emphasis on Bacillus subtilis (MIC value of 7.5 µM). Ravenelin’s antiparasitic activities were assessed against both the epimastigote (IC50 value of 5 ± 1 µM) and the intracellular amastigote forms of T. cruzi (IC50 value of 9 ± 2 µM), as well as against P. falciparum (IC50 value of 3.4 ± 0.4 µM). Ravenelin showed low cytotoxic effects on both HepG2 (CC50 > 50 µM) and peritoneal macrophage (CC50 = 185 ± 1 µM) cells with attractive selectivity for the parasites (SI values > 15). These findings indicate that ravenelin is a natural compound with both antibacterial and antiparasitic activities, and considerable selectivity indexes. Therefore, ravenelin is an attractive candidate for hit-to-lead development.  相似文献   

16.
Abstract— This study compared the ability of highly purified resting and activated DBA/2 mouse peritoneal macrophages to survive treatment with the photosensitizer benzoporphyrin derivative (BPD, verteporfin) and light. Culture of macrophages with recombinant murine interferon-γ (rIFN-γ, 100 U/mL) for 72 h imparted a phenotypic and functional activation by dramatically increasing cell surface expression of major histocompatibility complex Class II (Ia) molecules and the formation of nitric oxide. The rIFN-γ-activated macrophages were significantly (P < 0.05) more sensitive (lethal dose to cause a 50% reduction in cell survival, LD50= 14.4 ± 1.1 ng/mL) to photodynamic killing with BPD and light (10 J/cm2) than cells (LD50= 18.2 ± 2.0 ng/mL) cultured in medium alone. In contrast, macrophages treated with different concentrations of bacterial lipopolysaccharide (LPS) were as resistant or more resistant to photodynamic killing than cells cultured in medium alone. No cytotoxic effect of BPD was detected in cultures containing the drug but protected from light. Comparable amounts of BPD were taken up in vitro by unactivated and rIFN-γ-activated macrophages, as detected by flow cytometric analysis. However, cells cultured with LPS (10 μg/mL) took up more BPD than macrophages cultured in medium alone or with rIFN-γ. The DBA/2 P815 mastocytoma cells took up greater amounts of the drug and were subsequently more vulnerable to treatment with BPD and light (LD50= 6.9 ng/mL) than macrophages cultured under any condition. The explanation for the increased vulnerability of rIFN-γ-activated macrophages and the greater resistance of LPS-activated macrophages, relative to medium-cultured macrophages, to photodynamic killing with BPD is uncertain. However, the increased susceptibility of macrophages, activated with the immunomodulatory cytokine IFN-γ, to treatment with BPD and light might indicate how photodynamic therapy could interfere with the development of experimental autoimmune disease, conditions in which activated macrophages are known to be involved.  相似文献   

17.
《Analytical letters》2012,45(18):3411-3419
Abstract

Penicillin G (PG) in milk is unsafe for human and is a big problem for the foods industry. Hence, the better analytical and eliminative techniques are demanded. We investigated a PG molecular imprinted polymer (MIP), which can sensitively detect and extract the PG from milk and other samples. The MIP synthesis involved a β-lactam antibiotics PG, methacrylic acid (MAA) and dimethyl formamide (DMF). Its properties were analyzed with Scatchard plot, which showed that there were two affinity sites of the PG polymer. The first equilibrium dissociation constant of the high-affinity binding sites Kd1 was 1.14 × 10?4 mol/L and the binding capacity Qmax1 was 46.01 µmol/g; the second equilibrium dissociation constant of the low-affinity binding sites Kd2 was 1.35 × 10?3 mol/L and the binding capacity Qmax2 was 72.55 µmol/g. Furthermore, two PG determination methods using the polymer were developed. The first was carried out quantitatively with a spectrophotometer and the detection limit was 1 ppm. The other one was the combination of the MIP particles with milk fermentation for PG analysis and the sensitivity was 10 ppb.  相似文献   

18.
《Analytical letters》2012,45(8):1366-1374
Abstract

Chemiluminescence reaction of the system containing europium(III) ion, KMnO4, Na2SO3, and ibuprofen was investigated for the determination of ibuprofen. The introduction of Eu(III) ion into the system of KMnO4-Na2SO3-ibuprofen caused a significant increase in the chemiluminescence signal. The increment of the chemiluminescence signal is proportional to ibuprofen concentration in the range of 5.0 × 10?8–5.0 × 10?6 g/ml with a detection limit of 1 × 10?8 g/ml. The relative standard deviation for 1.0 × 10?7 g/ml ibuprofen solution was 1.7% (n = 11). The proposed method was successfully applied to determine ibuprofen in tablets and human plasma.  相似文献   

19.
In an attempt to develop new anti-inflammatory agents which act by co-release of carbon monoxide (CO) and a specialized pro-resolving mediator, we designed conjugates of a lipoxin A4 analogue and an acyloxycyclohexadiene-Fe(CO)3 complex as an esterase-triggered CO-releasing molecule (ET-CORM). After adjustment of the protecting group strategy, two of such compounds were successfully prepared by total synthesis (12 steps; 4–5 % overall yield) starting from deoxy-d -ribose and exploiting a Wittig olefination and an intermolecular Heck reaction as key C−C bond-forming steps. A crucial late reduction of an aryl-ketone moiety in the presence of a highly sensitive dienol ester functionality was achieved with BH3-SMe2 in the presence of catalytic amounts of NaBH4. Both target compounds were dose-dependently toxic towards cultured human umbilical vein endothelial cells (HUVEC), with LipET-CORM 1-A being slightly more toxic. While induction of heme oxygenase 1 (HO-1) in HUVEC was observed for both compounds, they did not inhibit TNF-α-mediated VCAM-1 expression in these cells. In M2 polarized macrophages HO-1 expression was more pronounced as compared to M1 polarized macrophages. In both types of macrophages HO-1 expression was downregulated by lipopolysaccharide, but only in M2 macrophages HO-1 expression was rescued by LipET-CORM. 15-Lipoxygenase (15-LO) was only expressed in M2 macrophages and was not influenced by LipET-CORM. Collectively our data demonstrate that LipET-CORMs induce HO-1 expression in endothelial cells and M2 polarized macrophages. The role of the intra-cellular released lipoxin A4 in resolution of inflammation, however, remains to be assessed.  相似文献   

20.
It was found that in acidic chloride media the complex of Mo(VI) with 1,10‐phenantroline induces catalytic reduction of KClO3. This catalytic effect can be utilized for sensitive differential pulse polarographic determination of Mo(VI) with a low detection limit of 2.9×10?11 M (2.8 ng/L). The optimal Mo(VI) response was obtained at pH 2.8, in the presence of (6–12)×10?5 M 1,10‐phenantroline and 2×10?2 M KClO3. The sensitivity was 1.73 nA/nM and the catalytic response was linear up to 7.5×10?7 M Mo (VI). The interferences from inorganic ions and surface‐active substances were investigated. The results of the determination of Mo(VI) in CRM water sample showed good reproducibility (R.S.D. for standard solution is below 1.2% and for water samples is 8.9%) and accuracy of the elaborated catalytic polarographic method.  相似文献   

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